Methods and compositions for reducing the symptoms of Parkinson's disease

Abstract

A method is disclosed for treating neurological or motor disorders, such as Parkinson's disease, in patients requiring a method for parenteral administration of levodopa and dopa decarboxylase inhibitors (DDCIs), such as carbidopa, benserazide, or any combination thereof.

Description

Related applications

[0001] Cross-reference of related applications

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 459,438 filed on 14 April 2023, U.S. Provisional Patent Application No. 63 / 508,634 filed on 16 June 2023, U.S. Patent Application No. 18 / 234,232 filed on 15 August 2023, and U.S. Provisional Patent Application No. 63 / 564,464 filed on 12 March 2024, the disclosures of each thereof being incorporated herein by reference in their entirety. [Technical Field]

[0002]

[0002] The present invention provides a method for treating neurological or motor disorders, such as Parkinson's disease, by parenteral administration of levodopa and dopa decarboxylase inhibitors (DDCIs), such as carbidopa, benserazide, or any combination thereof. [Background technology]

[0003]

[0003] Parkinson's disease is a degenerative disease characterized by a decrease in the concentration of the neurotransmitter dopamine in the brain. Levodopa (L-dopa or L-3,4-dihydroxyphenylalanine) is an immediately metabolized precursor of dopamine and, unlike dopamine, can cross the blood-brain barrier and is most commonly used to restore dopamine levels in the brain. For the past 40 years, levodopa has remained the most effective treatment for Parkinson's disease. [Overview of the project] [Problems that the invention aims to solve]

[0004]

[0004] However, levodopa has a short half-life in plasma, and even under optimal, normal, current clinical standards, it produces pulsatile dopaminergic stimulation. Long-term treatment can therefore be complicated by motor fluctuations and dyskinesia, which can cause significant disability in some patients. A therapeutic strategy that can ultimately deliver levodopa / dopamine to the brain in a more continuous and physiological manner would yield the benefits of standard levodopa in suppressing motor complications and is more strongly needed in patients with Parkinson's disease and other neurological or motor disorders. [Means for solving the problem]

[0005] Summary of the Invention

[0005] In particular, methods and pharmaceutical compositions for treating neurological or motor disorders are provided herein, including parenteral administration of levodopa or salts thereof (e.g., pharmaceutically acceptable salts thereof) and compositions containing them (e.g., pharmaceutically acceptable compositions, e.g., liquid pharmaceutical compositions), as well as dopa decarboxylase inhibitors (DDCIs) or salts thereof (e.g., pharmaceutically acceptable salts thereof) and compositions containing them (e.g., pharmaceutically acceptable compositions, e.g., liquid pharmaceutical compositions).

[0006]

[0006] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0007]

[0007] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0008]

[0008] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0009]

[0009] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0010]

[0010] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day and for about 2 or 3 days. Upon administration, the patient, An increase from baseline during a good on-time of a day, a decrease from baseline during a good on-time of a day in which moderate to severe dyskinesia is observed, or a combination of any of them such that at least one of them is shown, and the method is targeted.

[0011]

[0011] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0012]

[0012] An embodiment of the present invention is a method for treating a patient with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa substantially continuously for about 24 hours / day and for about 2 or 3 days, such that by the administration, the patient shows an increase from baseline during a good on-time of a day, a decrease from baseline during a good on-time of a day in which moderate to severe dyskinesia is observed, or a combination of any of them such that at least one of them is shown, and the method is targeted.

[0013]

[0013] An embodiment of the present invention is a method for treating a patient with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w substantially continuously for about 24 hours / day and for about 2 or 3 days, such that by the administration, the patient shows an increase from baseline during a good on-time of a day, a decrease from baseline during a good on-time of a day in which moderate to severe dyskinesia is observed, or a combination of any of them such that at least one of them is shown, and the method is targeted.

[0014]

[0014] Embodiments of the present invention are methods of treating a patient in whom Parkinson's disease is recognized, comprising subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days, by day 3 of the continuous administration, the patient exhibits by the administration an increase from baseline in good on-time per day, a decrease from baseline in on-time per day with moderate to severe dyskinesia, or a combination of any of them such that at least one of them is shown.

[0015]

[0015] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0016]

[0016] Embodiments of the present invention are methods of treating a patient in whom Parkinson's disease is recognized, comprising subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days, by day 3 of the continuous administration, the patient exhibits by the administration an increase from baseline in good on-time per day, a decrease from baseline in on-time per day with moderate to severe dyskinesia, or a combination of any of them such that at least one of them is shown.

[0017]

[0017] Embodiments of the present invention are methods of treating a patient in whom Parkinson's disease is recognized, comprising subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa in a ratio of about 8:1 w / w, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days, By the third consecutive day, the patient has received the treatment. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0018]

[0018] Embodiments of the present invention are methods for treating patients diagnosed with Parkinson's disease, The procedure includes the step of subcutaneously administering to a patient, substantially continuously for about 24 hours / day, a pharmaceutically acceptable liquid composition containing levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof. Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score. Improvement from baseline based on the Clinical Global Impression (CGI-C) score of change, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0019]

[0019] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Patient Global Impression (PGI-I) score. Improvement from baseline based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0020]

[0020] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0021]

[0021] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score. Improvement from baseline based on the Clinical Global Impression (CGI-C) score of change, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0022]

[0022] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Patient Global Impression (PGI-I) score. Improvement from baseline based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0023]

[0023] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score. Improvement from baseline based on the Clinical Global Impression (CGI-C) score of change, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0024]

[0024] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Patient Global Impression (PGI-I) score. Improvement from baseline based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0025]

[0025] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. Improvements from baseline in daily living activity, as assessed by the UPDRS Part III score, which represents a decrease from baseline, as defined in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0026]

[0026] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0027]

[0027] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0028]

[0028] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day, Two or three days after administration, the patient reacted to the administration. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0029]

[0029] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day and for about 2 to 3 days. Upon administration, the patient, Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0030]

[0030] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0031]

[0031] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day and for about 2 to 3 days, Upon administration, the patient, Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0032]

[0032] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for about 24 hours / day substantially continuously and for about 2 to 3 days. Upon administration, the patient, Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0033]

[0033] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days. By the third consecutive day, the patient has received the treatment. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0034]

[0034] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0035]

[0035] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days. By the third consecutive day, the patient has received the treatment. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0036]

[0036] Embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day and for a continuous period of about 2 to 3 days. By the third consecutive day, the patient has received the treatment. Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. A decrease from baseline in daily off-time, Increase from baseline in daily on-time without dyskinesia, Reduction from baseline in the total daily incidence of problematic dyskinesia. A decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement from baseline in daily living exercise experience as assessed by the UPDRS Part III score, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0037]

[0037] According to some embodiments, administration leads to patients showing an increase from baseline in good on time per day. According to some embodiments, administration leads to patients showing a decrease from baseline in on time per day with moderate to severe dyskinesia. According to some embodiments, administration leads to patients showing improvement from baseline based on the Subjective Global Impression (SGI-C) score of change. According to some embodiments, administration leads to patients showing improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement. According to some embodiments, administration leads to patients showing improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration leads to patients showing improvement from baseline based on the Clinical Global Impression (CGI-I) score of improvement.

[0038]

[0038] According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and a decrease from baseline in on time per day with moderate to severe dyskinesia. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and an improvement from baseline based on the Subjective Global Impression (SGI-C) score of change. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and an improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and an improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration results in patients showing a decrease from baseline in on time per day with moderate to severe dyskinesia and an improvement from baseline based on the Subjective Global Impression (SGI-C) score of change. According to several embodiments, administration results in patients showing a decrease from baseline in 24-hour on-times with moderate to severe dyskinesia, and improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement. According to several embodiments, administration results in patients showing a decrease from baseline in 24-hour on-times with moderate to severe dyskinesia, and improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to several embodiments, administration results in patients showing improvement from baseline based on the Subjective Global Impression (SGI-C) score of change, and improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to several embodiments, administration results in patients showing improvement from baseline based on the Patient Global Impression (PGI-C) score of change, and improvement from baseline based on the Clinical Global Impression (PGI-I) score of improvement.

[0039]

[0039] According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, moderate to severe dyskinesia, a decrease from baseline in on time per day, and improvement from baseline based on the Subjective Global Impression (SGI-C) score of change. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, moderate to severe dyskinesia, a decrease from baseline in on time per day, and improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, moderate to severe dyskinesia, a decrease from baseline in on time per day, and improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to several embodiments, administration results in patients showing an increase from baseline in good on time per day, an improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score, and an improvement from baseline based on the Clinical Global Impression of Change (CGI-C) score. According to several embodiments, administration results in patients showing an increase from baseline in good on time per day, an improvement from baseline based on the Patient Global Impression of Improvement (PGI-I) score, and an improvement from baseline based on the Clinical Global Impression of Improvement (CGI-I) score. According to several embodiments, administration results in patients showing a decrease from baseline in on time per day, an improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score, and an improvement from baseline based on the Clinical Global Impression of Change (CGI-C) score, even with moderate to severe dyskinesia. According to several embodiments, administration leads to patients showing a reduction from baseline in on-time per day with moderate to severe dyskinesia, improvement from baseline based on the Patient Global Impression-I (PGI-I) score of improvement, and improvement from baseline based on the Clinical Global Impression-I (CGI-I) score of improvement.

[0040]

[0040] According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in moderate to severe dyskinesia, improvement from baseline based on the Subjective Global Impression (SGI-C) score of change, and improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in moderate to severe dyskinesia, improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement, and improvement from baseline based on the Clinical Global Impression (CGI-I) score of improvement.

[0041]

[0041] According to several embodiments, administration results in the patient showing an increase from baseline in good on time per day. According to several embodiments, administration results in the patient showing a decrease from baseline in on time per day with moderate to severe dyskinesia. According to several embodiments, administration results in the patient showing a decrease from baseline in off time per day. According to several embodiments, administration results in the patient showing an increase from baseline in on time per day without dyskinesia. According to several embodiments, administration results in the patient showing a decrease from baseline in total daily problem dyskinesia. According to several embodiments, administration results in the patient showing improvement from baseline in daily activity experience as assessed by the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in a decrease from baseline on the revised UPDRS Part III score.

[0042]

[0042] According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and a decrease from baseline in on time per day with moderate to severe dyskinesia. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and a decrease from baseline in off time per day. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and an increase from baseline in on time per day without dyskinesia. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and a decrease from baseline in total problematic dyskinesia per day. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day and an improvement from baseline in daily exercise experience as assessed by the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in an increase from baseline in good on time per day and a decrease from baseline on the revised UPDRS Part III score. According to some embodiments, administration leads to patients showing a decrease from baseline in both on-time and off-time per day, with moderate to severe dyskinesia. According to some embodiments, administration leads to patients showing a decrease from baseline in both on-time and on-time per day, with moderate to severe dyskinesia, and an increase from baseline in both on-time and on-time per day, without dyskinesia. According to some embodiments, administration leads to patients showing a decrease from baseline in both on-time and on-time, with moderate to severe dyskinesia, and a decrease from baseline in the total daily amount of problematic dyskinesia.According to several embodiments, administration results in patients showing a decrease from baseline in daily on-time with moderate to severe dyskinesia, and an improvement from baseline in their daily exercise experience as assessed by the UPDRS Part III score, which is a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to several embodiments, administration results in patients showing a decrease from baseline in daily off-time, and an increase from baseline in daily on-time without dyskinesia. According to several embodiments, administration results in patients showing a decrease from baseline in daily off-time, and a decrease from baseline in the total daily amount of problematic dyskinesia. According to several embodiments, administration results in patients showing a decrease from baseline in daily off-time, and an improvement from baseline in their daily exercise experience as assessed by the UPDRS Part III score, which is a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to some embodiments, administration leads patients to show an increase from baseline in dyskinesia-free on-time per day and a decrease from baseline in total problematic dyskinesia per day. According to some embodiments, administration leads patients to show an increase from baseline in dyskinesia-free on-time per day and an improvement from baseline in daily activity experience, as assessed by the Revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, as proposed by the Movement Disorder Society.According to several embodiments, administration results in patients showing a decrease from baseline in the total daily amount of problematic dyskinesia and an improvement from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, which is a decrease from baseline on the revised UPDRS Part III score.

[0043]

[0043] According to some embodiments, administration results in the patient showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, and a decrease from baseline in off time per day. According to some embodiments, administration results in the patient showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, and an increase from baseline in on time per day without dyskinesia. According to some embodiments, administration results in the patient showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, and a decrease from baseline in the total daily problematic dyskinesia. According to several embodiments, administration results in patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, with an increase from baseline in good on time per day, a decrease from baseline in moderate to severe on time per day, and a decrease from baseline in the revised UPDRS Part III score. According to several embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in off time per day, and an increase from baseline in on time per day without dyskinesia. According to several embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in off time per day, and a decrease from baseline in the total daily amount of problematic dyskinesia.According to several embodiments, administration results in patients showing improved baseline-from-baseline activity in daily living, as assessed by the UPDRS Part III score, with an increase from baseline in good-on time per day, a decrease from baseline in off-time per day, and a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to several embodiments, administration results in patients showing improved baseline-from-baseline activity in daily living, an increase from baseline in good-on time per day, an increase from baseline in dyskinesia-free on time per day, and a decrease from baseline in the total dyskinesia per day. According to several embodiments, administration results in patients showing improved baseline-from-baseline activity in daily living, as assessed by the UPDRS Part III score, with an increase from baseline in good-on time per day, an increase from baseline in dyskinesia-free on time per day, and a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to several embodiments, administration results in patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, with an increase from baseline in good on time per day, a decrease from baseline in total problematic dyskinesia per day, and a decrease from baseline in the revised UPDRS Part III score. According to several embodiments, administration results in patients showing a decrease from baseline in moderate to severe on time per day, a decrease from baseline in off time per day, and an increase from baseline in on time per day without dyskinesia.According to several embodiments, administration leads to patients showing a decrease from baseline in daily on-time, daily off-time, and total daily problematic dyskinesia, with moderate to severe dyskinesia present. According to several embodiments, administration leads to patients showing a decrease from baseline in daily on-time, daily off-time, and a decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, with moderate to severe dyskinesia present. According to several embodiments, administration leads to patients showing a decrease from baseline in daily on-time, daily on-time, dyskinesia-free, and total daily problematic dyskinesia, with moderate to severe dyskinesia present. According to several embodiments, administration leads to patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in a decrease from baseline in daily on time with moderate to severe dyskinesia, an increase from baseline in daily on time without dyskinesia, and a decrease from baseline in the revised UPDRS Part III score.In some embodiments, administration results in patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, with a decrease from baseline in daily on time with moderate to severe dyskinesia, a decrease from baseline in total daily problematic dyskinesia, and a decrease from baseline in the revised UPDRS Part III score. In some embodiments, administration results in patients showing a decrease from baseline in daily off time, an increase from baseline in daily on time without dyskinesia, and a decrease from baseline in total daily problematic dyskinesia. According to several embodiments, administration results in patients showing improved daily exercise experience as assessed by the UPDRS Part III score, with a decrease from baseline in daily off-time, an increase from baseline in daily on-time without dyskinesia, and a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to several embodiments, administration results in patients showing improved daily exercise experience as assessed by the UPDRS Part III score, with a decrease from baseline in daily off-time, a decrease from baseline in total daily problematic dyskinesia, and a decrease from baseline in the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score.According to several embodiments, administration leads patients to show improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in an increase from baseline in dyskinesia-free on-time per day, a decrease from baseline in total dyskinesia per day, and a decrease from baseline in the revised UPDRS Part III score.

[0044]

[0044] According to some embodiments, administration results in the patient showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, a decrease from baseline in off time per day, and an increase from baseline in on time per day without dyskinesia. According to some embodiments, administration results in the patient showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, a decrease from baseline in off time per day, and a decrease from baseline in the total daily problematic dyskinesia. According to several embodiments, administration leads to patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in an increase from baseline in good daily on time, a decrease from baseline in moderate to severe daily on time, a decrease from baseline in daily off time, and a decrease from baseline in the revised UPDRS Part III score. According to several embodiments, administration leads to patients showing an increase from baseline in good daily on time, a decrease from baseline in daily off time, an increase from baseline in daily on time without dyskinesia, and a decrease from baseline in the total daily amount of problematic dyskinesia. According to several embodiments, administration leads patients to show improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in an increase from baseline in good on time per day, a decrease from baseline in off time per day, an increase from baseline in dyskinesia-free on time per day, and a decrease from baseline in the revised UPDRS Part III score.According to several embodiments, administration results in patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, including an increase from baseline in good daily on time, an increase from baseline in dyskinesia-free daily on time, a decrease from baseline in total dyskinesia per day, and a decrease from baseline in the revised UPDRS Part III score. According to several embodiments, administration results in patients showing a decrease from baseline in moderate to severe daily on time, a decrease from baseline in daily off time, an increase from baseline in dyskinesia-free daily on time, and a decrease from baseline in total dyskinesia per day. According to several embodiments, administration results in patients showing improved baseline activity in daily living as assessed by the UPDRS Part III score, with moderate to severe dyskinesia, a decrease from baseline in daily on time, a decrease from baseline in daily off time, an increase from baseline in daily on time without dyskinesia, and a decrease from baseline on the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score. According to several embodiments, administration results in patients showing improved baseline activity in daily living as assessed by the UPDRS Part III score, with moderate to severe dyskinesia, a decrease from baseline in daily on time, an increase from baseline in daily on time without dyskinesia, a decrease from baseline in total daily problematic dyskinesia, and a decrease from baseline on the revised Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score.According to several embodiments, administration leads patients to show improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in a decrease from baseline in daily off-time, an increase from baseline in daily on-time without dyskinesia, a decrease from baseline in total daily problematic dyskinesia, and a decrease from baseline in the revised UPDRS Part III score.

[0045]

[0045] According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, a decrease from baseline in off time per day, an increase from baseline in on time per day without dyskinesia, and a decrease from baseline in total problematic dyskinesia per day. According to some embodiments, administration results in patients showing an increase from baseline in good on time per day, a decrease from baseline in on time per day with moderate to severe dyskinesia, a decrease from baseline in off time per day, an increase from baseline in on time per day without dyskinesia, and a decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and an improvement from baseline in daily activity activity as assessed by the UPDRS Part III score. According to several embodiments, administration leads to patients showing improvements from baseline in their daily exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in a decrease from baseline in daily on time with moderate to severe dyskinesia, a decrease from baseline in daily off time, an increase from baseline in daily on time without dyskinesia, a decrease from baseline in total daily problematic dyskinesia, and a decrease from baseline in the revised UPDRS Part III score.

[0046]

[0046] According to several embodiments, administration results in patients showing improvements from baseline in their daily exercise experience, as assessed by the UPDRS Part III score, including an increase from baseline in good on time per day, a decrease from baseline in moderate to severe on time per day, a decrease from baseline in off time per day, an increase from baseline in on time per day without dyskinesia, a decrease from baseline in total problematic dyskinesia per day, and a decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score as proposed by the Movement Disorder Society.

[0047]

[0047] Some embodiments of the present invention are methods for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa, carbidopa, and arginine substantially continuously for about 24 hours / day, The pharmaceutically acceptable liquid composition contains approximately 60 mg / mL levodopa and 7.5 mg / mL carbidopa, and the pharmaceutically acceptable liquid composition is administered to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa to the patient over a period of approximately 24 hours. Two or three days after administration, the patient Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate at least one of the following.

[0048]

[0048] According to some embodiments, an increase from baseline in good on-time per day is an increase from baseline of at least about 0.3 to 3.5 hours in good on-time per day, and moderate to severe dyskinesia is observed. A decrease from baseline in on-time per day is a decrease from baseline of at least about 0.3 to 2.5 hours in moderate to severe dyskinesia is observed.

[0049]

[0049] According to some embodiments, the method further includes administering to a patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

[0050]

[0050] According to some embodiments, the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to some embodiments, the low-activity flow rate at night is applied for about 6 hours or about 8 hours, and the high-activity flow rate at daytime is applied for about 18 hours or about 16 hours, respectively. According to some embodiments, the low-activity flow rate at night is about 0.08 mL / hour. According to some embodiments, the high-activity flow rate at daytime is about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour or about 0.32 mL / hour.

[0051]

[0051] Some embodiments of the present invention are methods for increasing good on time in patients diagnosed with Parkinson's disease, The step includes subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of approximately 8:1 w / w to a patient for approximately 2 to 3 consecutive days, substantially continuously for approximately 24 hours / day. The study targets methods in which administration results in an increase of at least approximately 0.3 to 3.5 hours from baseline in the good daily on time, up to three consecutive days.

[0052]

[0052] According to some embodiments, administration results in an increase of approximately 1.8 hours from baseline in good on time per day.

[0053] According to some embodiments, the pharmaceutically acceptable liquid composition further comprises arginine. According to some embodiments, the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa.

[0053]

[0054] According to some embodiments, a pharmaceutically acceptable liquid composition is administered to a patient to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa over a period of approximately 24 hours.

[0054]

[0055] According to some embodiments, the method further includes administering to a patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

[0055]

[0056] According to several embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to several embodiments, the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours. According to several embodiments, the low-activity flow rate at night is about 0.08 mL / hour. According to several embodiments, the high-activity flow rate during the day is about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

[0056]

[0057] A further embodiment of the present invention is a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, The step includes subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of approximately 8:1 w / w to a patient substantially continuously for about 24 hours / day. Upon administration, the patient, Increased daily on-time without problematic dyskinesia, A decrease in the amount of time spent off-duty each day. A decrease in the revised Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, as assessed by the Movement Disorder Society, indicates improvement in daily living exercise experience. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof It will show at least one of the following: Improvement in patients was measured compared to patients treated with levodopa in immediate-release oral form. The improvements observed in patients are as follows: The daily on time without problematic dyskinesia is an increase of approximately 1.7 hours. The daily off-time is reduced by approximately 1.4 hours. Daily living activity, as assessed by the UPDRS Part II score, decreased by approximately 3.0. The odds ratio for the Patient Global Impression (PGI-C) score of change is approximately 5.3. The Clinical Global Impression-I (CGI-I) score for improvement has an odds ratio of approximately 7.2, and this method is targeted.

[0057]

[0058] According to some embodiments, the pharmaceutically acceptable liquid composition further comprises arginine. According to some embodiments, the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa. According to some embodiments, the pharmaceutically acceptable liquid composition is administered to deliver about 720 mg of levodopa and about 90 mg of carbidopa to the patient over a period of about 24 hours.

[0058]

[0059] According to several embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to several embodiments, the low-activity flow rate at night is applied for about 6 hours or about 8 hours, and the high-activity flow rate at daytime is applied for about 18 hours or about 16 hours, the low-activity flow rate at night being about 0.08 mL / hour and the high-activity flow rates at daytime being about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour or about 0.32 mL / hour.

[0059]

[0060] Some embodiments of the present invention relate to a method for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w, and further containing arginine, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days. By the third consecutive day, the patient has received the treatment. An increase of at least approximately 0.3 to 3.5 from baseline during good on-times of the day. Moderate to severe dyskinesia is observed, with a decrease of at least approximately 0.3 to 2.5 hours from baseline in daily on-time. A decrease of at least 0.1 to 2.0 from the baseline during off-hours per day. An increase of at least approximately 0.1 to 3.5 from baseline during on-hours of the day without dyskinesia. A reduction of at least 0.1 to 3.2 from baseline in the total daily incidence of problematic dyskinesia. A decrease of approximately 2 to 13 points from baseline in the UPDRS Part III score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0060]

[0061] According to some embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient via a device comprising a control station, reusable parts, and disposable parts.

[0061]

[0062] According to some embodiments, the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa. According to some embodiments, the pharmaceutically acceptable liquid composition is administered to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa to the patient over a period of approximately 24 hours.

[0062]

[0063] According to several embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to several embodiments, the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours. According to several embodiments, the low-activity flow rate at night is about 0.08 mL / hour, and the high-activity flow rates during the day are about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

[0063]

[0064] According to some embodiments, the patient is fully awake approximately 5 hours after administration at a first flow rate.

[0065] According to some embodiments, patients show improvement from baseline in sleep quality two days after treatment. According to some embodiments, patients show change from baseline in sleep quality two days after treatment.

[0064]

[0066] Some embodiments of the present invention are methods for treating patients diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa, carbidopa, and arginine to the patient substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days. The pharmaceutically acceptable liquid composition contains approximately 60 mg / mL levodopa and 7.5 mg / mL carbidopa, and the pharmaceutically acceptable liquid composition is administered to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa to the patient over a period of approximately 24 hours. By the third consecutive day, the patient has received the treatment. An increase of at least approximately 0.3 to 3.5 from baseline during good on-times of the day. Moderate to severe dyskinesia is observed, with a decrease of at least approximately 0.3 to 2.5 hours from baseline in daily on-time. A decrease of at least 0.1 to 2.0 from the baseline during off-hours per day. An increase of at least approximately 0.1 to 3.5 from baseline during on-hours of the day without dyskinesia. A reduction of at least 0.1 to 3.2 from baseline in the total daily incidence of problematic dyskinesia. A decrease of approximately 2 to 13 points from baseline in the UPDRS Part III score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0065]

[0067] According to some embodiments, the method further includes the step of administering to a patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

[0066]

[0068] According to some embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient via a device comprising a control station, reusable parts, and disposable parts.

[0067]

[0069] According to several embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to several embodiments, the low-activity flow rate at night is applied for about 6 hours or about 8 hours, and the high-activity flow rate at daytime is applied for about 18 hours or about 16 hours, respectively. According to several embodiments, the low-activity flow rate at night is about 0.08 mL / hour, and the high-activity flow rates at daytime are about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

[0068]

[0070] According to some embodiments, the patient is fully awake approximately 5 hours after administration at a first flow rate.

[0071] According to some embodiments, patients show improvement from baseline in sleep quality two days after treatment. According to some embodiments, patients show change from baseline in sleep quality two days after treatment.

[0069]

[0072] Some embodiments of the present invention are methods for increasing good on time in patients diagnosed with Parkinson's disease, The step involves subcutaneously administering to a patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of approximately 8:1 w / w, and further containing arginine, substantially continuously for about 24 hours / day for about 2 to 3 consecutive days. The study targets methods in which administration results in an increase of at least approximately 0.3 to 3.5 hours from baseline in the good daily on time, up to three consecutive days.

[0070]

[0073] According to some embodiments, administration results in an increase of approximately 1.8 hours from baseline in good on time per day.

[0074] According to some embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient via a device comprising a control station, reusable parts, and disposable parts.

[0071]

[0075] According to some embodiments, the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa. According to some embodiments, the pharmaceutically acceptable liquid composition is administered to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa to the patient over a period of approximately 24 hours.

[0072]

[0076] According to some embodiments, the method further includes administering to a patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

[0073]

[0077] According to several embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during the daytime and the second flow rate being a low-activity flow rate during the nighttime. According to several embodiments, the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours. According to several embodiments, the low-activity flow rate at night is about 0.08 mL / hour. According to several embodiments, the high-activity flow rate during the day is about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

[0074]

[0078] According to some embodiments, the patient is fully awake approximately 5 hours after administration at a first flow rate.

[0079] According to some embodiments, patients show improvement from baseline in sleep quality two days after treatment. According to some embodiments, patients show change from baseline in sleep quality two days after treatment.

[0075]

[0080] According to any embodiment described herein, an increase from baseline in good on-times per day is an increase from baseline of at least about 0.1 to 3.5 hours in good on-times per day.

[0076]

[0081] According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.11 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.12 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.13 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.14 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.15 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.16 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 0.17 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 0.18 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 0.19 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 0.20 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 0.22 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.24 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.26 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.28 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.32 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.34 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.36 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.38 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.42 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.44 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.46 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.48 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.55 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.65 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.75 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.85 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.95 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.0 hour from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.1 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.0 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.2 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.25 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.75 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 2.8 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 2.9 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.0 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.1 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.2 hours from baseline in good on-time per day.According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.25 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.3 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.4 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 3.5 hours from baseline in good on-time per day.

[0077]

[0082] According to any embodiment described herein, a decrease from baseline in on-time per day in which moderate to severe dyskinesia is observed is a decrease from baseline of at least about 0.3 to 2.5 hours of on-time per day in which moderate to severe dyskinesia is observed.

[0078]

[0083] According to some embodiments, a decrease from baseline in on-time per day for moderate to severe dyskinesia is a decrease of approximately 0.3 hours from baseline in on-time per day. According to some embodiments, a decrease from baseline in on-time per day for moderate to severe dyskinesia is a decrease of approximately 0.32 hours from baseline in on-time per day for moderate to severe dyskinesia. According to some embodiments, a decrease from baseline in on-time per day for moderate to severe dyskinesia is a decrease of approximately 0.34 hours from baseline in on-time per day for moderate to severe dyskinesia. According to some embodiments, a decrease from baseline in on-time per day for moderate to severe dyskinesia is a decrease of approximately 0.36 hours from baseline in on-time per day for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.38 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.4 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.42 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.44 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the reduction from baseline in on-time per day in which moderate to severe dyskinesia is observed is approximately a reduction from baseline of 0.46 hours of on-time per day in which moderate to severe dyskinesia is observed.According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.48 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.5 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.55 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.6 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.65 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.7 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.75 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is approximately 0.8 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, a baseline reduction in on-time per day with moderate to severe dyskinesia corresponds to a baseline reduction of approximately 0.85 hours of on-time per day with moderate to severe dyskinesia.According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 0.9 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 0.95 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1 hour from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.1 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.2 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.3 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.4 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.5 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the reduction from baseline in 24-hour on-time with moderate to severe dyskinesia is approximately 1.6 hours from baseline in 24-hour on-time with moderate to severe dyskinesia.According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.7 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.8 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 1.9 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 2 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 2.1 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 2.1 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 2.3 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, the decrease from baseline in daily on-time for moderate to severe dyskinesia is a decrease of approximately 2.4 hours from baseline in daily on-time for moderate to severe dyskinesia. According to some embodiments, a decrease from baseline in 24-hour on-time with moderate to severe dyskinesia corresponds to a decrease of approximately 2.5 hours from baseline in 24-hour on-time with moderate to severe dyskinesia.

[0079]

[0084] According to any embodiment described herein, the reduction from baseline in daily off-time is approximately 0.1 to 2.0 hours from baseline in daily off-time.

[0080]

[0085] According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.1 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.11 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.12 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.13 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.14 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.15 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.16 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.17 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.18 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.19 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.20 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.22 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.24 hours from baseline in the total daily off-time.According to some embodiments, an increase from baseline in good on-time per day is approximately an increase of 0.26 hours in total off-time per day. According to some embodiments, an increase from baseline in good on-time per day is approximately an increase of 0.28 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.3 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.32 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.34 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.36 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.38 hours in total off-time per day. According to some embodiments, a decrease from baseline in off-time per day is approximately a decrease of 0.4 hours in total off-time per day. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.42 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.44 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.46 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.48 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.5 hours from baseline in the total daily off-time.According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.55 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.6 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.65 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.7 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.75 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.8 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.85 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.9 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 0.95 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.0 hour from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.1 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.2 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.3 hours from baseline in the total daily off-time.According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.4 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.5 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.6 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.7 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.8 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.8 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 1.9 hours from baseline in the total daily off-time. According to some embodiments, the decrease from baseline in daily off-time is a decrease of approximately 2.0 hours from baseline in the total daily off-time.

[0081]

[0086] It should be noted that daily off-hours and total daily off-hours are interchangeable herein unless otherwise specifically mentioned or understood to be otherwise by those skilled in the art.

[0082]

[0087] According to any embodiment described herein, the increase from baseline in dyskinesia-free on-hours is an increase from baseline of at least about 0.1 to 3.5 hours of dyskinesia-free on-hours.

[0083]

[0088] According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.1 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.11 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.12 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.13 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.14 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 0.15 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 0.16 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 0.17 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 0.18 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 0.19 hours from baseline in dyskinesia-free on-day time.According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.20 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.22 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.24 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.26 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.28 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.3 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.32 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.34 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.36 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.38 hours from baseline in dyskinesia-free on-time per day.According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.4 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.42 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.44 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.46 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.48 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.5 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.55 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.6 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.65 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.7 hours from baseline in dyskinesia-free on-time per day.According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.75 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.8 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.85 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.9 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 0.95 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.0 hour from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.1 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.2 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.3 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.4 hours from baseline in dyskinesia-free on-time per day.According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.5 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.6 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.7 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.8 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, an increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.8 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 1.9 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.0 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.1 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.2 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.25 hours from baseline in dyskinesia-free on-time per day.According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.3 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.4 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.5 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.6 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.7 hours from baseline in dyskinesia-free on-time per day. These are increases. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.75 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.8 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 2.9 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 3.0 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-time per day is an increase of approximately 3.1 hours from baseline in dyskinesia-free on-time per day. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 3.2 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 3.25 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 3.3 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 3.4 hours from baseline in dyskinesia-free on-day time. According to some embodiments, the increase from baseline in dyskinesia-free on-day time is approximately 3.5 hours from baseline in dyskinesia-free on-day time.

[0084]

[0089] According to any embodiment described herein, a baseline reduction in the total daily duration of problematic dyskinesia is a baseline reduction of approximately 0.1 to 3.2 hours in the total daily duration of problematic dyskinesia.

[0085]

[0090] According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.1 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.11 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.12 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.13 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.14 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.15 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.16 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.17 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.18 hours from baseline in the total daily amount of problematic dyskinesia.According to some embodiments described herein, the decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.19 hours from baseline in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, the decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.20 hours from baseline in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, the decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.22 hours from baseline in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, the decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.24 hours from baseline in the total daily time spent on problematic dyskinesia. According to some embodiments, the increase from baseline in good on time per day is an increase of approximately 0.26 hours from baseline in the total daily time spent on problematic dyskinesia. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.28 hours in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, a decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.3 hours in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, a decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.32 hours in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, a decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.34 hours in the total daily time spent on problematic dyskinesia. According to some embodiments described herein, a decrease from baseline in the total daily time spent on problematic dyskinesia is a decrease of approximately 0.36 hours in the total daily time spent on problematic dyskinesia.According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.38 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.4 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.42 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.44 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.46 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.48 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.5 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.55 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.6 hours from baseline in the total daily amount of problematic dyskinesia.According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.65 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.7 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.75 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.8 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 0.85 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.9 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 0.95 hours from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 1.0 hour from baseline in total problematic dyskinesia per day. According to some embodiments described herein, the daily reduction in problematic dyskinesia from baseline is a reduction of approximately 1.1 hours from baseline in total problematic dyskinesia per day.According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.2 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.3 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.4 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.5 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.6 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.7 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.8 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.8 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 1.9 hours from baseline in the total daily amount of problematic dyskinesia.According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 2.0 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 2.1 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 2.2 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 2.3 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 2.4 hours from baseline in the total daily amount of problematic dyskinesia. This is a decrease from baseline. According to some embodiments described herein, the decrease in the total daily amount of problematic dyskinesia from baseline is a decrease of approximately 2.5 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the decrease in the total daily amount of problematic dyskinesia from baseline is a decrease of approximately 2.6 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the decrease in the total daily amount of problematic dyskinesia from baseline is a decrease of approximately 2.7 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the decrease in the total daily amount of problematic dyskinesia from baseline is a decrease of approximately 2.8 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the decrease in the total daily amount of problematic dyskinesia from baseline is a decrease of approximately 2.9 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 3.0 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 3.1 hours from baseline in the total daily amount of problematic dyskinesia. According to some embodiments described herein, the reduction from baseline in the total daily amount of problematic dyskinesia is a reduction of approximately 3.2 hours from baseline in the total daily amount of problematic dyskinesia.

[0086]

[0091] According to any of the embodiments described herein, improvements from baseline in daily living activity, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 2 to 13 points from baseline in the UPDRS Part III score.

[0087]

[0092] According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 2 to 3 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 3 to 4 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 4 to 5 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 5 to 6 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 6 to 7 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 7 to 8 points from baseline in the UPDRS Part III score.According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 8 to 9 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 9 to 10 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 10 to 11 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living activity, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 11 to 12 points from baseline in the UPDRS Part III score. According to some embodiments, improvements from baseline in daily living activity, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, result in a decrease of approximately 12 to 13 points from baseline in the UPDRS Part III score.

[0088]

[0093] According to some embodiments, the increase from baseline in good on-times per day lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0089]

[0094] According to several embodiments, the reduction from baseline in daily on-time, in which moderate to severe dyskinesia is observed, lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0090]

[0095] According to some embodiments, the reduction from baseline in daily off-time lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0091]

[0096] According to some embodiments, the increase from baseline in dyskinesia-free on-hours per day persists for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0092]

[0097] According to some embodiments, the reduction from baseline in the total daily amount of problematic dyskinesia lasts for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0093]

[0098] According to several embodiments, improvements from baseline in daily living exercise experience, as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, resulting in a decrease from baseline in the revised UPDRS Part III score, are sustained for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0094]

[0099] According to several embodiments, the improvement in the Subjective Global Impression (SGI-C) score of the change lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0095]

[0100] According to several embodiments, the improvement in the Clinical Global Impression (CGI-C) score of the change lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0096]

[0101] According to several embodiments, the improvement in the Patient Global Impression-I score lasts for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0097]

[0102] According to several embodiments, the improvement in the Clinical Global Impression-I (CGI-I) score lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0098]

[0103] A further embodiment of the present invention is a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvements in daily living exercise experiences were assessed using the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0099]

[0104] A further embodiment of the present invention is a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvements in daily living exercise experiences were assessed using the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0100]

[0105] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0101]

[0106] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0102]

[0107] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0103]

[0108] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0104]

[0109] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0105]

[0110] In some embodiments, administration leads to patients showing a further reduction in problematic dyskinesia throughout the day.

[0111] A further embodiment of the present invention is a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvements in daily living exercise experiences were assessed using the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0106]

[0112] A further embodiment of the present invention is a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition comprising levodopa or a pharmaceutically acceptable salt thereof, and optionally carbidopa or a pharmaceutically acceptable salt thereof, substantially continuously for about 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvements in daily living exercise experiences were assessed using the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0107]

[0113] According to some embodiments, the pharmaceutically acceptable liquid composition comprises levodopa or a pharmaceutically acceptable salt thereof, and carbidopa or a pharmaceutically acceptable salt thereof.

[0108]

[0114] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0109]

[0115] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day, Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0110]

[0116] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0111]

[0117] Further embodiments of the present invention provide a method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day. Upon administration, the patient, A decrease in the amount of time spent off-duty each day. Increased daily on-time without problematic dyskinesia, Improvement in daily living exercise experiences, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) scores proposed by the Movement Disorder Society. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression (CGI-I) score. Reduction of problematic dyskinesia in one day, or any combination thereof This focuses on methods that demonstrate at least one of the following:

[0112]

[0118] According to some embodiments, administration results in a reduction in 24-hour off-time. According to some embodiments, administration results in an increase in 24-hour on-time without problematic dyskinesia. According to some embodiments, administration results in an improvement in daily living exercise experience as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society. According to some embodiments, administration results in an improvement based on the Patient Global Impression Change (PGI-C) score. According to some embodiments, administration results in an improvement based on the Clinical Global Impression Change (CGI-I) score. According to some embodiments, administration results in an improvement based on the Clinical Global Impression Change (CGI-C) score. According to some embodiments, administration results in a reduction in 24-hour problematic dyskinesia.

[0113]

[0119] According to some embodiments, administration results in a decrease in 24-hour off-time and an increase in 24-hour on-time without problematic dyskinesia. According to some embodiments, administration results in a decrease in 24-hour off-time and an improvement in daily living exercise experience as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society. According to some embodiments, administration results in a decrease in 24-hour off-time and an improvement based on the Patient Global Impression Change (PGI-C) score. According to some embodiments, administration results in a decrease in 24-hour off-time and an improvement based on the Clinical Global Impression Improvement (CGI-I) score. According to some embodiments, administration results in an improvement based on the Clinical Global Impression Change (CGI-C) score. According to some embodiments, administration results in a decrease in 24-hour off-time and a decrease in 24-hour problematic dyskinesia. According to several embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia and improved daily activity experience as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society. According to several embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia and improvement based on the Patient Global Impression Change (PGI-C) score. According to several embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia and improvement based on the Clinical Global Impression Change (CGI-I) score. According to several embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia and a decrease in 24-hour problematic dyskinesia. According to several embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia and improvement based on the Clinical Global Impression Change (CGI-C) score.According to some embodiments, administration results in improvements in the motor experience in daily living, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvements based on the Global Patient Impression of Change (PGI-C) score. According to some embodiments, administration results in improvements in the motor experience in daily living, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvements based on the Global Clinical Impression of Improvement (CGI-I) score. According to some embodiments, administration results in improvements in the motor experience in daily living, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvements based on the Global Clinical Impression of Change (CGI-C) score. According to several embodiments, administration results in improvements in daily living activity experience and a reduction in 24-hour problematic dyskinesia, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society. According to several embodiments, administration results in improvements based on the Patient Global Impression (PGI-C) score and improvements based on the Clinical Global Impression (CGI-I) score. According to several embodiments, administration results in improvements based on the Patient Global Impression (PGI-C) score and improvements based on the Clinical Global Impression (CGI-C) score. According to several embodiments, administration results in improvements in the Patient Global Impression (PGI-C) score and a reduction in 24-hour problematic dyskinesia. According to several embodiments, administration results in improvements based on the Clinical Global Impression (CGI-C) score and a reduction in 24-hour problematic dyskinesia.According to several embodiments, administration results in improvement based on the Clinical Global Impression-I score and a reduction in problematic dyskinesia throughout the day.

[0114]

[0120] According to several embodiments, administration results in a reduction in 24-hour off-time, 24-hour on-time without problematic dyskinesia, and improvements in daily living exercise experience as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society. According to several embodiments, administration results in a reduction in 24-hour off-time, 24-hour on-time without problematic dyskinesia, and improvements based on the Patient Global Impression (PGI-C) score of change. According to several embodiments, administration results in a reduction in 24-hour off-time, 24-hour on-time without problematic dyskinesia, and improvements based on the Clinical Global Impression (CGI-I) score of improvement. According to several embodiments, administration results in a reduction in 24-hour off-time, 24-hour on-time without problematic dyskinesia, and improvements based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration results in a reduction in 24-hour off-time, 24-hour on-time without problematic dyskinesia, and 24-hour problematic dyskinesia. According to some embodiments, administration results in a reduction in 24-hour off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and improvement based on the Patient Global Impression of Change (PGI-C) score. According to some embodiments, administration results in a reduction in 24-hour off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and improvement based on the Clinical Global Impression of Improvement (CGI-I) score as proposed by the Movement Disorder Society.According to several embodiments, administration results in a reduction in daily off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and a reduction in daily problematic dyskinesia. According to several embodiments, administration results in a reduction in daily off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score proposed by the Movement Disorder Society, and improvement based on the Clinical Global Impression (CGI-C) score of change. According to several embodiments, administration results in a reduction in daily off-time, improvement based on the Patient Global Impression (PGI-C) score of change, and improvement based on the Clinical Global Impression (CGI-I) score of improvement. According to several embodiments, administration results in a reduction in daily off-time, improvement based on the Patient Global Impression (PGI-C) score of change, and a reduction in daily problematic dyskinesia. According to some embodiments, administration results in a reduction in 24-hour off-time, improvement based on the Patient Global Impression (PGI-C) score of change, and improvement based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration results in an increase in 24-hour on-time without problematic dyskinesia, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and improvement based on the Patient Global Impression (PGI-C) score of change.According to some embodiments, administration results in an increase in problematic dyskinesia-free on-time per day, improvement in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and improvement based on the Clinical Gross Impression of Improvement (CGI-I) score. According to some embodiments, administration results in an increase in problematic dyskinesia-free on-time per day, improvement in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and improvement based on the Clinical Gross Impression of Change (CGI-C) score. According to some embodiments, administration results in an increase in 24-hour on time without problematic dyskinesia, an improvement in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and a reduction in 24-hour problematic dyskinesia. According to some embodiments, administration results in an improvement in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) or Part III (UPDRS Part III) score as assessed by a revised version of the Movement Disorder Society, an improvement based on the Global Patient Impression of Change (PGI-C) score, and an improvement based on the Clinical Global Impression of Improvement (CGI-I) score. According to several embodiments, administration results in improvements in the motor experience of daily living as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score or a revised version of the UPDRS Part III score, improvements based on the Patient Global Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-C) score.

[0115]

[0121] According to some embodiments, administration results in a reduction in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, improvements in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score, and improvements based on the Patient Global Impression of Change (PGI-C) score. According to some embodiments, administration results in a reduction in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, improvements in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score, and improvements based on the Clinical Global Impression of Improvement (CGI-I) score. According to some embodiments, administration results in a reduction in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, an improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and a reduction in 24-hour problematic dyskinesia. According to some embodiments, administration results in a reduction in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, an improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, and an improvement based on the Clinical Global Impression of Change (CGI-C) score.According to some embodiments, administration results in a reduction in daily off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score, improvement based on the Patient Global Impression of Change (PGI-C) score, and improvement based on the Clinical Global Impression of Improvement (CGI-I) score. According to some embodiments, administration results in a reduction in daily off-time, improvement in the experience of daily living activities as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score, improvement based on the Patient Global Impression of Change (PGI-C) score, and a reduction in daily problematic dyskinesia. According to some embodiments, administration results in a reduction in 24-hour off-time, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, improvements based on the Patient Global Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-C) score. According to some embodiments, administration results in an increase in 24-hour on-time without problematic dyskinesia, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II score as proposed by the Movement Disorder Society, improvements based on the Patient Global Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-I) score.According to some embodiments, administration results in an increase in on-time per day without problematic dyskinesia, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, improvements based on the Global Patient Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-C) score as proposed by the Movement Disorder Society. According to some embodiments, administration results in an increase in on-time per day without problematic dyskinesia, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score, improvements based on the Global Patient Impression of Change (PGI-C) score, and a decrease in problematic dyskinesia per day.

[0116]

[0122] According to several embodiments, administration results in a decrease in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, improvements based on the Global Patient Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-I) score. According to several embodiments, administration results in a decrease in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, improvements in the motor experience of daily living as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II score as proposed by the Movement Disorder Society, improvements based on the Global Patient Impression of Change (PGI-C) score, and improvements based on the Clinical Global Impression of Change (CGI-C) score. According to several embodiments, administration results in a reduction in 24-hour off-time, an increase in 24-hour on-time without problematic dyskinesia, improvements in daily activity experience as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) or Part III (UPDRS Part III) score as proposed by the Movement Disorder Society, improvements based on the Patient Global Impression of Change (PGI-C) score, and a reduction in 24-hour problematic dyskinesia.

[0117]

[0123] According to any of the embodiments described above, the reduction in daily off-time is a reduction of at least approximately ≥25% from the baseline in daily off-time.

[0124] According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥25% from the baseline in daily off-time. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥30% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥35% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥40% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥45% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥50% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥55% from the baseline in daily off-time for the patient. According to some embodiments, the daily reduction in off-time is a reduction of approximately ≥60% from the baseline in daily off-time for the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥65% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥70% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥75% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥80% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥85% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥90% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is a reduction of approximately ≥95% of the baseline daily off-time in the patient. According to some embodiments, a daily reduction in off-time is the elimination of off-time.

[0118]

[0125] According to any embodiment described herein, the reduction in off-hours per day is the reduction from the baseline during off-hours per day.

[0126] According to any embodiment described herein, the reduction in 12-day off-time is the reduction in 12-day off-time compared to patients treated with an immediate-release oral formulation of levodopa.

[0119]

[0127] According to any embodiment described herein, the reduction in 12-day off-time is the reduction in 12-day off-time compared to the administration of an immediate-release oral formulation of levodopa.

[0120]

[0128] According to any of the embodiments described herein, the reduction in daily off-time is a reduction of at least about 0.1 to 3.5 hours of daily off-time. According to some embodiments, the reduction in daily off-time is a reduction of at least about 0.1 to 6 hours of daily off-time.

[0121]

[0129] According to any of the embodiments described herein, the reduction in daily off-time is a reduction from a baseline of at least about 0.1 to 3.5 hours of daily off-time. According to some embodiments, the reduction in daily off-time is a reduction from a baseline of at least about 0.1 to 6 hours of daily off-time.

[0122]

[0130] According to any embodiment described herein, the reduction in daily off-time is at least about 0.1 to 3.5 hours compared to patients treated with an immediate-release oral formulation of levodopa. According to any embodiment described herein, the reduction in daily off-time is at least about 0.1 to 6 hours compared to patients treated with an immediate-release oral formulation of levodopa.

[0123]

[0131] According to any of the embodiments described herein, the reduction in daily off-time is at least about 0.1 to 3.5 hours of daily off-time compared to administration of an immediate-release oral formulation of levodopa. According to any of the embodiments described herein, the reduction in daily off-time is at least about 0.1 to 6 hours of daily off-time compared to administration of an immediate-release oral formulation of levodopa.

[0124]

[0132] According to some embodiments, the reduction in daily off-time is approximately 0.1 hours. According to some embodiments, the reduction in daily off-time is approximately 0.15 hours. According to some embodiments, the reduction in daily off-time is approximately 0.2 hours. According to some embodiments, the reduction in daily off-time is approximately 0.25 hours. According to some embodiments, the reduction in daily off-time is approximately 0.3 hours. According to some embodiments, the reduction in daily off-time is approximately 0.35 hours. According to some embodiments, the reduction in daily off-time is approximately 0.4 hours. According to some embodiments, the reduction in daily off-time is approximately 0.45 hours. According to some embodiments, the reduction in daily off-time is approximately 0.5 hours. According to some embodiments, the reduction in daily off-time is approximately 0.55 hours. According to some embodiments, the reduction in daily off-time is approximately 0.6 hours. According to some embodiments, the reduction in daily off-time is approximately 0.65 hours. According to some embodiments, the reduction in daily off-time is approximately 0.7 hours. According to some embodiments, the reduction in daily off-time is approximately 0.75 hours. According to some embodiments, the reduction in daily off-time is approximately 1 hour. According to some embodiments, the reduction in daily off-time is approximately 0.8 hours. According to some embodiments, the reduction in daily off-time is approximately 0.85 hours. According to some embodiments, the reduction in daily off-time is approximately 0.9 hours.According to some embodiments, the reduction in daily off-time is approximately 0.95 hours. According to some embodiments, the reduction in daily off-time is approximately 1 hour. According to some embodiments, the reduction in daily off-time is approximately 1.1 hours. According to some embodiments, the reduction in daily off-time is approximately 1.2 hours. According to some embodiments, the reduction in daily off-time is approximately 1.3 hours. According to some embodiments, the reduction in daily off-time is approximately 1.4 hours. According to some embodiments, the reduction in daily off-time is approximately 1.5 hours. According to some embodiments, the reduction in daily off-time is approximately 1.6 hours. According to some embodiments, the reduction in daily off-time is approximately 1.7 hours. According to some embodiments, the reduction in daily off-time is approximately 1.8 hours. According to some embodiments, the reduction in daily off-time is approximately 1.9 hours. According to some embodiments, the reduction in daily off-time is approximately 2 hours. According to some embodiments, the reduction in daily off-time is approximately 2.1 hours. According to some embodiments, the reduction in daily off-time is approximately 2.2 hours. According to some embodiments, the reduction in daily off-time is approximately 2.3 hours. According to some embodiments, the reduction in daily off-time is approximately 2.4 hours. According to some embodiments, the reduction in daily off-time is approximately 2.5 hours. According to some embodiments, the reduction in daily off-time is approximately 2.6 hours.According to some embodiments, the reduction in daily off-time is approximately 2.7 hours. According to some embodiments, the reduction in daily off-time is approximately 2.8 hours. According to some embodiments, the reduction in daily off-time is approximately 2.9 hours. According to some embodiments, the reduction in daily off-time is approximately 3 hours. According to some embodiments, the reduction in daily off-time is approximately 3.1 hours. According to some embodiments, the reduction in daily off-time is approximately 3.2 hours. According to some embodiments, the reduction in daily off-time is approximately 3.3 hours. According to some embodiments, the reduction in daily off-time is approximately 3.4 hours. According to some embodiments, the reduction in daily off-time is approximately 3.5 hours. According to some embodiments, the reduction in daily off-time is approximately 3.6 hours. According to some embodiments, the reduction in daily off-time is approximately 3.7 hours. According to some embodiments, the reduction in daily off-time is approximately 3.8 hours. According to some embodiments, the reduction in daily off-time is approximately 3.9 hours. According to some embodiments, the reduction in daily off-time is approximately 4 hours. According to some embodiments, the reduction in daily off-time is approximately 4.1 hours. According to some embodiments, the reduction in daily off-time is approximately 4.2 hours. According to some embodiments, the reduction in daily off-time is approximately 4.3 hours. According to some embodiments, the reduction in daily off-time is approximately 4.4 hours.According to some embodiments, the reduction in daily off-time is approximately 4.5 hours. According to some embodiments, the reduction in daily off-time is approximately 4.6 hours. According to some embodiments, the reduction in daily off-time is approximately 4.7 hours. According to some embodiments, the reduction in daily off-time is approximately 4.8 hours. According to some embodiments, the reduction in daily off-time is approximately 4.9 hours. According to some embodiments, the reduction in daily off-time is approximately 5 hours. According to some embodiments, the reduction in daily off-time is approximately 5.1 hours. According to some embodiments, the reduction in daily off-time is approximately 5.2 hours. According to some embodiments, the reduction in daily off-time is approximately 5.3 hours. According to some embodiments, the reduction in daily off-time is approximately 5.4 hours. According to some embodiments, the reduction in daily off-time is approximately 5.5 hours. According to some embodiments, the reduction in daily off-time is approximately 5.6 hours. According to some embodiments, the reduction in daily off-time is approximately 5.7 hours. According to some embodiments, the reduction in daily off-time is approximately 5.8 hours. According to some embodiments, the reduction in daily off-time is approximately 5.9 hours. According to some embodiments, the reduction in daily off-time is approximately 6 hours.

[0125]

[0133] According to some embodiments, the reduction in daily off-time lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0126]

[0134] According to any embodiment described herein, the increase in on-hours per day without problematic dyskinesia is the increase from baseline in on-hours per day without problematic dyskinesia.

[0127]

[0135] According to any embodiment described herein, the increase in problematic dyskinesia-free on-time per day is the increase in problematic dyskinesia-free on-time per day compared to patients treated with an immediate-release oral formulation of levodopa.

[0128]

[0136] According to any embodiment described herein, the increase in problematic dyskinesia-free on-time per day is the increase in problematic dyskinesia-free on-time per day with respect to administration of an immediate-release oral formulation of levodopa.

[0129]

[0137] According to any embodiment described herein, the increase in on-time per day without problematic dyskinesia is an increase of at least about 0.1 to 3.5 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is an increase of at least about 0.1 to 6 hours of on-time per day without problematic dyskinesia.

[0130]

[0138] According to any embodiment described herein, the increase in on-day time without problematic dyskinesia is an increase from a baseline of at least about 0.1 to 3.5 hours of on-day time without problematic dyskinesia. According to some embodiments, the increase in on-day time without problematic dyskinesia is an increase from a baseline of at least about 0.1 to 6 hours of on-day time without problematic dyskinesia.

[0131]

[0139] According to any embodiment described herein, the increase in problematic dyskinesia-free on-day time is at least about 1 to 3.5 hours compared to patients treated with an immediate-release oral formulation of levodopa. According to any embodiment described herein, the increase in problematic dyskinesia-free on-day time is at least about 1 to 6 hours compared to patients treated with an immediate-release oral formulation of levodopa.

[0132]

[0140] According to any embodiment described herein, the increase in problematic dyskinesia-free on-time per day is at least about 1 to 3.5 hours of problematic dyskinesia-free on-time per day compared to administration of an immediate-release oral formulation of levodopa. According to any embodiment described herein, the increase in problematic dyskinesia-free on-time per day is at least about 1 to 6 hours of problematic dyskinesia-free on-time per day compared to administration of an immediate-release oral formulation of levodopa.

[0133]

[0141] According to some embodiments, the increase in on-time per day without problematic dyskinesia is an increase of approximately 1 hour in on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is an increase of approximately 1.1 hours in on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is an increase of approximately 1.2 hours in on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is an increase of approximately 1.3 hours in on-time per day without problematic dyskinesia. According to some embodiments, in patients, the improvement in on-time per day without problematic dyskinesia is an increase of approximately 1.4 hours in on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.5 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.6 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.7 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.72 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.8 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 1.9 hours of on-time per day without problematic dyskinesia.According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.1 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.2 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.3 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.4 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.5 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.6 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.7 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.8 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 2.9 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3 hours of on-time per day without problematic dyskinesia.According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.1 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.2 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.3 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.4 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.5 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.6 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.7 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.8 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 3.9 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.1 hours of on-time per day without problematic dyskinesia.According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.2 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.3 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.4 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.5 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.6 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.7 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.8 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 4.9 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.1 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.2 hours of on-time per day without problematic dyskinesia.According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.3 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.4 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.5 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.6 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.7 hours. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.8 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 5.9 hours of on-time per day without problematic dyskinesia. According to some embodiments, the increase in on-time per day without problematic dyskinesia is approximately 6 hours of on-time per day without problematic dyskinesia.

[0134]

[0142] According to some embodiments, the increase in on-hours per day without problematic dyskinesia persists for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0135]

[0143] According to any embodiment described herein, a reduction in daily problematic dyskinesia is a reduction from baseline of daily problematic dyskinesia.

[0144] According to any embodiment described herein, the reduction in problematic dyskinesia over a day is the reduction in problematic dyskinesia over a day compared to patients treated with an immediate-release oral formulation of levodopa.

[0136]

[0145] According to any embodiment described herein, the reduction in problematic dyskinesia over a day is the reduction in problematic dyskinesia over a day in response to administration of an immediate-release oral formulation of levodopa.

[0137]

[0146] According to some embodiments, a daily reduction in problematic dyskinesia is a reduction of at least about 0.1 to 3.5 hours of problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is a reduction of at least about 0.1 to 6 hours of problematic dyskinesia.

[0138]

[0147] According to some embodiments, a daily reduction in problematic dyskinesia is a reduction of at least about 0.1 to 3.5 hours from baseline. According to some embodiments, a daily reduction in problematic dyskinesia is a reduction of at least about 0.1 to 6 hours from baseline.

[0139]

[0148] According to some embodiments, the reduction in 24-hour problematic dyskinesia is at least about 0.1 to 3.5 hours of 24-hour problematic dyskinesia compared to patients treated with an immediate-release oral formulation of levodopa. According to some embodiments, the reduction in 24-hour problematic dyskinesia is at least about 0.1 to 6 hours of 24-hour problematic dyskinesia compared to patients treated with an immediate-release oral formulation of levodopa.

[0140]

[0149] According to some embodiments, the reduction in 24-hour problematic dyskinesia is at least about 0.1 to 3.5 hours of 24-hour problematic dyskinesia compared to administration of an immediate-release oral formulation of levodopa. According to some embodiments, the reduction in 24-hour problematic dyskinesia is at least about 0.1 to 6 hours of 24-hour problematic dyskinesia compared to administration of an immediate-release oral formulation of levodopa.

[0141]

[0150] According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.1 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.15 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.2 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.25 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.35 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.45 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.55 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.6 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.65 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.7 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 0.75 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately a 1-hour reduction in problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately a 0.8-hour reduction in problematic dyskinesia.According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 0.85 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 0.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 0.95 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 1 hour of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 1.1 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 1.2 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is a reduction of approximately 1.3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.6 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.7 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.8 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 1.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 2.1 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 2.2 hours of daily problematic dyskinesia.According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.6 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.7 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.8 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 2.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.1 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.2 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.6 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 3.7 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 3.8 hours of daily problematic dyskinesia.According to some embodiments, a reduction in daily problematic dyskinesia is approximately 3.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.1 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.2 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.3 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.4 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.6 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.7 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.8 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 4.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.1 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.2 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 5.3 hours of daily problematic dyskinesia. According to some embodiments, a daily reduction in problematic dyskinesia is approximately 5.4 hours of daily problematic dyskinesia.According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.5 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.6 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.7 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.8 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 5.9 hours of daily problematic dyskinesia. According to some embodiments, a reduction in daily problematic dyskinesia is approximately 6 hours of daily problematic dyskinesia.

[0142]

[0151] According to any embodiment described herein, this refers to an improvement from baseline in daily living exercise experience, as assessed by the UPDRS Part III score, resulting in a decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society.

[0143]

[0152] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease in the UPDRS Part II score compared to patients treated with an immediate-release oral formulation of levodopa.

[0144]

[0153] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease in the UPDRS Part II score in response to administration of an immediate-release oral formulation of levodopa.

[0145]

[0154] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of at least about 1.5 to about 4.5 on the UPDRS Part II score.

[0146]

[0155] According to any embodiment described herein, improvement in daily living activity, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease from baseline of at least about 1.5 to about 4.5 on the UPDRS Part II score.

[0147]

[0156] According to several embodiments, improvement in the experience of daily living activities, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a reduction of at least approximately 1.5 to approximately 4.5 on the UPDRS Part II score compared to patients treated with an immediate-release oral formulation of levodopa.

[0148]

[0157] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of at least about 1.5 to about 4.5 on the UPDRS Part II score in response to administration of an immediate-release oral formulation of levodopa.

[0149]

[0158] According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 1.5 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 1.6 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 1.7 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 1.8 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 1.9 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 2.0 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 2.2 in the UPDRS Part II score.According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 2.4 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 2.6 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 2.8 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 3.0 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 3.2 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 3.4 points on the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 3.6 points on the UPDRS Part II score.According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 3.8 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 4.0 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 4.2 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, is a decrease of approximately 4.4 in the UPDRS Part II score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, corresponds to a decrease of approximately 4.5 points on the UPDRS Part II score.

[0150]

[0159] . . . . . . . . . . . . . . . . .

[0160] According to several embodiments, improvements in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part II (UPDRS Part II) score proposed by the Movement Disorder Society, last for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0151]

[0161] According to any embodiment described herein, this refers to an improvement from baseline in daily living exercise experience, as assessed by the UPDRS Part III score, resulting in a decrease from baseline in the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society.

[0152]

[0162] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a reduction in the UPDRS Part III score compared to patients treated with an immediate-release oral formulation of levodopa.

[0153]

[0163] According to any embodiment described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease in the UPDRS Part III score in response to administration of an immediate-release oral formulation of levodopa.

[0154]

[0164] According to any embodiment described herein, improvement in daily living activity, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of at least about 2 to about 50 points on the UPDRS Part III score.

[0155]

[0165] According to any embodiment described herein, improvement in daily living activity experience, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease from baseline of at least about 2 to about 50 on the UPDRS Part III score.

[0156]

[0166] According to any embodiment described herein, improvement in the experience of daily living activities, as assessed by a revised version of the Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a reduction of at least about 2 to about 50 points on the UPDRS Part III score compared to patients treated with an immediate-release oral formulation of levodopa.

[0157]

[0167] According to any of the embodiments described herein, improvement in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of at least about 2 to about 50 points on the UPDRS Part III score in response to administration of an immediate-release oral formulation of levodopa.

[0158]

[0168] According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 2 to 3 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 3 to 4 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 4 to 5 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 5 to 7.5 points on the UPDRS Part III score. According to several embodiments, improvement in motor experience in daily living, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, corresponds to a decrease of approximately 7.5 to approximately 10 points on the UPDRS Part III score. According to several embodiments, improvement in motor experience in daily living, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, corresponds to a decrease of approximately 10 to approximately 15 points on the UPDRS Part III score. According to several embodiments, improvement in motor experience in daily living, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, corresponds to a decrease of approximately 15 to approximately 20 points on the UPDRS Part III score.According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 20 to 30 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 30 to 40 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 40 to 50 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity (DDI) as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society corresponds to a decrease of approximately 7 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 8 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 8 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 9 points on the UPDRS Part III score.According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 10 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 11 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 12 points on the UPDRS Part III score. According to several embodiments, improvement in daily living activity, as assessed by the revised Unified Parkinson's Disease Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, is a decrease of approximately 13 points on the UPDRS Part III score.

[0159]

[0169] According to several embodiments, improvements in daily living activity experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score proposed by the Movement Disorder Society, last for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0160]

[0170] According to some embodiments, improvement in the Patient Global Impression (PGI-C) score of change is expressed as an odds ratio from baseline.

[0171] According to some embodiments, the improvement in the Patient Global Impression (PGI-C) score of the change is an odds ratio compared to patients treated with an immediate-release oral formulation of levodopa.

[0161]

[0172] According to some embodiments, the improvement in the patient's overall impression (PGI-C) score is an odds ratio compared to the administration of an immediate-release oral formulation of levodopa.

[0173] According to several embodiments, the odds ratio for improvement based on the Patient Global Impression-C score of change is at least about 2.4 to about 11.0.

[0162]

[0174] According to several embodiments, the odds ratio for improvement based on the Patient Global Impression-C score of change is at least about 2.4 to about 11.0 from baseline.

[0175] According to several embodiments, the improvement in the Patient Global Impression (PGI-C) score of change is an odds ratio of at least about 2.4 to about 11.0 compared to patients treated with an immediate-release oral formulation of levodopa.

[0163]

[0176] According to several embodiments, the improvement in the patient's overall impression (PGI-C) score for change is an odds ratio of at least about 2.4 to about 11.0 compared to administration of an immediate-release oral formulation of levodopa.

[0164]

[0177] According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 2.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 2.6. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 2.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 3.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 3.2. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 3.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression (PGI-C) score of change is approximately 3.6. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is 3.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 4.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 4.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 4.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 5.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 5.3. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 5.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 6.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 6.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 7.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C score of change is approximately 7.5.According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 8.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 8.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 9.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 9.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 10.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 10.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Impression-C (PGI-C) score of change is approximately 11.0.

[0165]

[0178] According to several embodiments, the improvement in the Patient Global Impression (PGI-C) score of change lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0166]

[0179] According to some embodiments, improvement based on the Patient Global Impression-I score is the odds ratio from baseline.

[0180] According to some embodiments, improvement based on the Patient Global Impression-I (PGI-I) score is an odds ratio compared to patients treated with an immediate-release oral formulation of levodopa.

[0167]

[0181] According to some embodiments, improvement based on the Patient Global Impression-I score is an odds ratio compared to administration of an immediate-release oral formulation of levodopa.

[0182] According to several embodiments, the odds ratio for improvement based on the Patient Global Impression-I score is at least about 2.0 to about 11.0.

[0168]

[0183] According to some embodiments, improvement based on the Patient Global Impression-I score represents an odds ratio of at least about 2.0 to about 11.0 from baseline.

[0184] According to several embodiments, improvement based on the Global Patient Impression (PGI-I) score represents odds ratios of at least about 2.0 to about 11.0 compared to patients treated with an immediate-release oral formulation of levodopa.

[0169]

[0185] According to several embodiments, improvement based on the Global Patient Impression (PGI-I) score is an odds ratio of at least about 2.0 to about 11.0 compared to administration of an immediate-release oral formulation of levodopa.

[0170]

[0186] According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 2.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 2.6. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 2.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 3.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 3.2. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 3.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 3.6. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is 3.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 4.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 4.4. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 4.8. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 5.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 5.3. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 5.5. According to some embodiments, the odds ratio for improvement based on the patient's global impression index (PGI-I) score is approximately 6.0. According to some embodiments, the odds ratio for improvement based on the patient's global impression index (PGI-I) score is approximately 6.5. According to some embodiments, the odds ratio for improvement based on the patient's global impression index (PGI-I) score is approximately 7.0. According to some embodiments, the odds ratio for improvement based on the patient's global impression index (PGI-I) score is approximately 7.5.According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 8.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 8.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 9.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 9.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 10.0. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 10.5. According to some embodiments, the odds ratio for improvement based on the Global Patient Influence (PGI-I) score of impressions is approximately 11.0.

[0171]

[0187] According to several embodiments, improvements based on the Patient Global Impression-I (PGI-I) score of improvement last for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0172]

[0188] According to some embodiments, improvement in the Clinical Global Impression (CGI-C) score of change is the odds ratio from baseline.

[0189] According to some embodiments, the improvement in the Clinical Global Impression (CGI-C) score of change is an odds ratio compared to patients treated with an immediate-release oral formulation of levodopa.

[0173]

[0190] According to some embodiments, the improvement in the Clinical Global Impression (CGI-C) score of the change is an odds ratio compared to the administration of an immediate-release oral formulation of levodopa.

[0191] According to several embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.0 to about 15.0.

[0174]

[0192] According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 3.0 to about 15.0 from baseline.

[0193] According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 3.0 to about 15.0 compared to patients treated with immediate-release oral formulations of levodopa.

[0175]

[0194] According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 3.0 to about 15.0 relative to the administration of immediate-release oral formulations of levodopa.

[0176]

[0195] According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.0. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.2. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.4. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.6. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 3.8. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 4.0. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 4.4. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 4.8. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 5.0. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 5.5. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 6.0. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 6.5. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 7.0. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 7.2. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 7.5. According to some embodiments, the odds ratio for improvement based on the Clinical Global Impression (CGI-C) score of change is at least about 8.0.According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 8.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 9.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 9.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 10.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 10.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 11.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 11.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 12.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 12.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 13.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 13.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 14.0. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 14.5. According to some embodiments, the improvement based on the Clinical Global Impression of Change (CGI-C) score is an odds ratio of at least about 15.0.

[0177]

[0196] According to several embodiments, the improvement in the Clinical Global Impression (CGI-C) score of the change lasts for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0178]

[0197] According to any of the embodiments described herein, administration results in the patient showing improvement in sleep quality as assessed by the Parkinson's Disease Sleep Scale 2 (PDSS-2) score.

[0179]

[0198] According to some embodiments, improvement in sleep quality, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is represented by a decrease in the PDSS-2 score.

[0180]

[0199] According to some embodiments, improvement in sleep quality, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is defined as a decrease from baseline in the PDSS-2 score.

[0181]

[0200] According to several embodiments, improvement in sleep quality, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease in the PDSS-2 score compared to patients treated with an immediate-release oral formulation of levodopa.

[0182]

[0201] According to some embodiments, improvement in sleep quality, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease in the PDSS-2 score in response to administration of an immediate-release oral formulation of levodopa.

[0183]

[0202] According to some embodiments, improvement in sleep, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease of at least about 1 to about 30 points on the PDSS-2 score.

[0184]

[0203] According to some embodiments, improvement in sleep, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease of at least about 1 to about 30 from baseline in the PDSS-2 score.

[0185]

[0204] According to several embodiments, improvement in sleep, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease of at least about 1 to about 30 points in the PDSS-2 score compared to patients treated with an immediate-release oral formulation of levodopa.

[0186]

[0205] According to several embodiments, the improvement in sleep, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease of at least about 1 to about 30 points in the PDSS-2 score in response to administration of an immediate-release oral formulation of levodopa.

[0187]

[0206] According to some embodiments, improvement in sleep, as assessed by the Parkinson's Disease Sleep Scale II (PDSS-2) score, is a decrease of at least about 1 to about 30 points on the PDSS-2 score.

[0188]

[0207] According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 1 to about 2 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 2 to about 3 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 3 to about 4 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 4 to about 5 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 5 to about 10 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 10 to about 15 in the PDSS-2 score. According to some embodiments, an improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 15 to about 20 in the PDSS-2 score. According to some embodiments, improvement in sleep, as assessed by the PDSS-2 score, is a decrease of at least about 20 to about 30 points on the PDSS-2 score.

[0189]

[0208] According to several embodiments, improvements in sleep, as assessed by the PDSS-2 score, last for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0190]

[0209] According to any of the embodiments described herein, administration results in improved sleep for the patient. According to some embodiments, substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein improves the patient's sleep. According to some embodiments, about 10% to about 75% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to some embodiments, about 10% to about 20% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to some embodiments, about 20% to about 30% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to some embodiments, about 30% to about 40% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to several embodiments, about 40% to about 50% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to several embodiments, about 50% to about 60% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to several embodiments, about 60% to about 75% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein. According to several embodiments, about 50% of patients benefit from substantially continuous subcutaneous administration of the pharmaceutically acceptable liquid composition detailed herein.

[0191]

[0210] According to some embodiments, one day after treatment, the patient shows improvement from baseline in sleep quality. According to some embodiments, two days after treatment, the patient shows improvement from baseline in sleep quality. According to some embodiments, three days after treatment, the patient shows improvement from baseline in sleep quality.

[0211] According to some embodiments, upon administration, the patient will show an improvement in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score.

[0192]

[0212] According to some embodiments, upon administration, the patient will show an improvement from baseline in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score.

[0193]

[0213] According to some embodiments, upon administration, the patient will show an improvement in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score compared to a patient treated with an immediate release oral formulation of levodopa.

[0194]

[0214] According to some embodiments, upon administration, the patient will show an improvement in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score over administration of an immediate release oral formulation of levodopa.

[0195]

[0215] According to some embodiments, upon administration, the patient will show an improvement in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score, the improvement being at least about a 1 to about a 30 decrease in the PDQ-39 score.

[0196]

[0216] According to some embodiments, upon administration, the patient will show an improvement in quality of life (QoL) as evaluated by the Parkinson's Disease Questionnaire (PDQ-39) score, the improvement being at least about a 1 to about a 30 decrease from baseline in the PDQ-39 score.

[0197]

[0217] According to several embodiments, administration leads to patients showing improvement in quality of life (QoL), as assessed by the Parkinson's Disease Questionnaire (PDQ-39) score, with improvements ranging from at least about 1 to about 30 points in the PDQ-39 score compared to patients treated with an immediate-release oral formulation of levodopa.

[0198]

[0218] According to several embodiments, administration leads to patients showing improvement in quality of life (QoL), as assessed by the Parkinson's Disease Questionnaire (PDQ-39) score, with the improvement being at least about 1 to about 30 points in the PDQ-39 score compared to administration of an immediate-release oral formulation of levodopa.

[0199]

[0219] According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 1 to about 2 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 2 to about 3 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 3 to about 4 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 4 to about 5 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 5 to about 10 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 10 to about 15 in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 15 to about 20 points in the PDQ-39 score. According to some embodiments, an improvement in QoL as assessed by the PDQ-39 score is a decrease of at least about 20 to about 30 points in the PDQ-39 score.

[0200]

[0220] According to several embodiments, improvements in QoL, as assessed by the PDQ-39 score, last for at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months.

[0201]

[0221] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for about 2 or 3 days, The study targets methods that result in an increase of at least approximately 0.3 to approximately 3.5 hours from baseline in good daily on time after administration.

[0202]

[0222] Further embodiments of the present invention are methods for increasing good on time in patients diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for at least about 28 days, The study targets methods that result in an increase of at least approximately 1.5 to approximately 6.0 hours from baseline in good daily on-time after administration.

[0203]

[0223] Further embodiments of the present invention are methods for increasing good on time in patients diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for at least about 28 days, The study targets methods that result in an increase of at least approximately 1.5 to approximately 8.5 hours from baseline in good daily on time after administration.

[0204]

[0224] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for about 2 or 3 days substantially continuously for about 24 hours / day. The study targets methods that result in an increase of at least approximately 0.3 to approximately 3.5 hours from baseline in good daily on time after administration.

[0205]

[0225] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for about 24 hours / day substantially continuously for at least about 28 days. The study targets methods that result in an increase of at least approximately 1.5 to approximately 6.0 hours from baseline in good daily on-time after administration.

[0206]

[0226] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for about 24 hours / day substantially continuously for at least about 28 days. The study targets methods that result in an increase of at least approximately 1.5 to approximately 8.5 hours from baseline in good daily on time after administration.

[0207]

[0227] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for about 2 to 3 consecutive days. The study targets methods in which administration results in an increase of at least approximately 0.3 to approximately 3.5 hours from baseline in the good daily on time, up to three consecutive days.

[0208]

[0228] Further embodiments of the present invention are methods for increasing good on time in patients diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for at least about 28 consecutive days. The study includes methods in which administration results in an increase of at least approximately 1.5 to approximately 6.0 hours from baseline in good daily on time, up to 28 consecutive days.

[0209]

[0229] Further embodiments of the present invention are methods for increasing good on time in patients with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa to the patient substantially continuously for about 24 hours / day for at least about 28 consecutive days, The study targets methods in which administration results in an increase of at least approximately 1.5 to approximately 8.5 hours from baseline in good daily on time, up to 28 consecutive days.

[0210]

[0230] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for about 2 to 3 consecutive days substantially continuously for about 24 hours / day. The study targets methods in which administration results in an increase of at least approximately 0.3 to approximately 3.5 hours from baseline in the good daily on time, up to three consecutive days.

[0211]

[0231] A further embodiment of the present invention is a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for at least about 28 consecutive days substantially 24 hours / day. The study includes methods in which administration results in an increase of at least approximately 1.5 to approximately 6.0 hours from baseline in good daily on time, up to 28 consecutive days.

[0212]

[0232] Further embodiments of the present invention relate to a method for increasing good on time in a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w to the patient substantially continuously for about 24 hours / day for at least about 28 consecutive days, wherein by the 28th consecutive day, the administration results in an increase from baseline of at least about 1.5 to about 8.5 hours of good on time per day.

[0213]

[0233] According to some embodiments, the increase from baseline in good on-time per day is an increase of at least about 0.3 to 6.0 hours of good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of at least about 0.3 to 3.5 hours of good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of at least about 1.5 to 8.5 hours of good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of at least about 1.5 to 6.0 hours of good on-time per day.

[0214]

[0234] According to some embodiments, the increase from baseline in good on time per day is achieved after 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 days or more of treatment. According to some embodiments, the increase from baseline in good on time per day is an increase of at least about 2.0 hours, at least about 2.1 hours, at least about 2.2 hours, at least about 2.3 hours, at least about 2.4 hours, or at least about 2.5 hours after treatment for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, or 36 months. According to some embodiments, the increase from baseline in good on time per day is at least about 2.5 hours, at least about 2.6 hours, at least about 2.7 hours, at least about 2.8 hours, at least about 2.9 hours, or at least about 3 hours after treatment for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, or 36 months. According to some embodiments, the increase from baseline in good on time per day is at least about 4 hours, at least about 4.1 hours, at least about 4.2 hours, at least about 4.3 hours, at least about 4.4 hours, or at least about 4.5 hours after treatment for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, or 36 months. According to some embodiments, the increase from baseline in good on-time per day is an increase of at least about 7.5 hours, at least about 7.6 hours, at least about 7.7 hours, at least about 7.8 hours, at least about 7.9 hours, or at least about 8 hours after treatment for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, or 36 months.

[0215]

[0235] According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.32 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.34 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.36 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.38 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.42 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.44 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.46 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.48 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.55 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.65 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.75 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.85 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 0.95 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1 hour from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.3 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 1.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.25 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.5 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.75 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 2.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.0 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.25 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.5 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 3.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.0 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 4.8 hours from baseline in good on-time per day.According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 4.9 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 5.0 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 5.1 hours from baseline in good on-time per day. According to some embodiments, the increase from baseline in good on-time per day is an increase of approximately 5.2 hours from baseline in good on-time per day. According to some embodiments, good on-time per day. An increase from baseline in time is an increase of approximately 5.3 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.4 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.5 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.6 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.7 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.8 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 5.9 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on time per day is an increase of approximately 6.0 hours from baseline in good on time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.5 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 6.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.5 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.6 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.7 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.8 hours from baseline in good on-time per day.According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 7.9 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8.1 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8.2 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8.3 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8.4 hours from baseline in good on-time per day. According to some embodiments, an increase from baseline in good on-time per day is an increase of approximately 8.5 hours from baseline in good on-time per day.

[0216]

[0236] According to some embodiments, the pharmaceutically acceptable liquid composition is administered for a period of time of more than about 1 year, more than about 2 years, more than about 3 years, more than about 4 years, more than about 5 years, more than about 6 years, more than about 7 years, more than about 8 years, more than 9 years, or more than 10 years.

[0217]

[0237] According to some embodiments, a pharmaceutically acceptable liquid composition is administered for a period of at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 6 years, at least about 7 years, at least about 8 years, at least about 9 years, or at least about 10 years.

[0218]

[0238] According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about two years results in an improvement in treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about three years results in an improvement in treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about four years results in an improvement in treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about five years results in an improvement in treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about six years results in improved treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about seven years results in improved treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about eight years results in improved treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year. According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about nine years results in improved treatment-dependent adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about one year.According to several embodiments, substantially continuous subcutaneous administration of a pharmaceutically acceptable liquid composition for a period of at least about 10 years results in improved treatment-induced adverse events (TEAEs) compared to administration of the pharmaceutically acceptable liquid composition for a period of about 1 year.

[0219]

[0239] According to some embodiments, the adverse events (TEAEs) that occur during the procedure are severe. According to some embodiments, the adverse events (TEAEs) that occur during the procedure are serious.

[0220]

[0240] According to some embodiments, the adverse event (TEAE) that occurred during the procedure is a drug-related TEAE. According to some embodiments, the drug-related TEAE is an injection site reaction. According to some embodiments, the adverse event (TEAE) that occurred during the procedure is an injection site reaction.

[0221]

[0241] According to some embodiments, the patient's daily wake time is standardized to approximately 14 to 18 hours. According to some embodiments, the patient's daily wake time is standardized to approximately 14 hours. According to some embodiments, the patient's daily wake time is standardized to approximately 15 hours. According to some embodiments, the patient's daily wake time is standardized to approximately 16 hours. According to some embodiments, the patient's daily wake time is standardized to approximately 17 hours. According to some embodiments, the patient's daily wake time is standardized to approximately 18 hours.

[0222]

[0242] According to some embodiments, the pharmaceutically acceptable liquid composition further comprises arginine.

[0243] According to some embodiments, a pharmaceutically acceptable liquid composition further comprises at least one antioxidant.

[0223]

[0244] According to some embodiments, a pharmaceutically acceptable liquid composition comprises about 7.5 mg / mL carbidopa and about 60 mg / mL levodopa.

[0245] According to some embodiments, a pharmaceutically acceptable liquid composition is administered to deliver approximately 370 mg, approximately 420 mg, approximately 470 mg, approximately 520 mg, approximately 570 mg, approximately 620 mg, approximately 670 mg, or approximately 720 mg of levodopa to a patient over a period of approximately 24 hours. According to some embodiments, a pharmaceutically acceptable liquid composition is administered to deliver approximately 720 mg of levodopa and approximately 90 mg of carbidopa to a patient over a period of approximately 24 hours.

[0224]

[0246] According to some embodiments, a pharmaceutically acceptable liquid composition is administered subcutaneously to a patient over a 24-hour period at a first flow rate and a second flow rate, the first flow rate being a high-activity flow rate during daytime hours and the second flow rate being a low-activity flow rate during nighttime hours.

[0225]

[0247] According to some embodiments, a low-activity flow rate is applied at night for about 8 hours, and a high-activity flow rate is applied during the day for about 16 hours. According to some embodiments, a low-activity flow rate is applied at night for about 6 hours, and a high-activity flow rate is applied during the day for about 18 hours.

[0226]

[0248] According to some embodiments, the low-activity flow rate at night is approximately 0.08 mL / hour. According to some embodiments, the low-activity flow rate at night is approximately 0.04 mL / hour.

[0249] According to some embodiments, the daytime high-activity flow rates are approximately 0.64 mL / hour, approximately 0.59 mL / hour, approximately 0.55 mL / hour, approximately 0.50 mL / hour, approximately 0.45 mL / hour, approximately 0.41 mL / hour, approximately 0.36 mL / hour, or approximately 0.32 mL / hour. According to some embodiments, the daytime high-activity flow rates are approximately 0.32 mL / hour, approximately 0.295 mL / hour, approximately 0.275 mL / hour, approximately 0.25 mL / hour, approximately 0.225 mL / hour, approximately 0.205 mL / hour, approximately 0.18 mL / hour, or approximately 0.16 mL / hour.

[0227]

[0250] According to some embodiments, the method further includes administering to a patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

[0228]

[0251] According to some embodiments, pharmaceutically acceptable oral compositions include one of 50 mg levodopa, 75 mg levodopa, 95 mg levodopa, 100 mg levodopa, 125 mg levodopa, 145 mg levodopa, 150 mg levodopa, 195 mg levodopa, 200 mg levodopa, 245 mg levodopa, or 250 mg levodopa.

[0229]

[0252] According to some embodiments, a pharmaceutically acceptable oral composition is oral levodopa for morning administration.

[0253] In some embodiments, neurological or motor disorders related to the methods described herein include: Parkinson's disease; secondary parkinsonian syndromes, e.g., drug-induced secondary parkinsonian syndrome, neuroleptic-induced parkinsonian syndrome, post-encephalitis parkinsonian syndrome, and vascular parkinsonian syndrome; motor fluctuations; neurodegenerative disorders; dyskinesia; decreased dopamine levels in the brain; levodopa-induced dyskinesia; rapid eye movement sleep behavior disorder (RBD); dystonia; morning akinesia; and tremor symptoms, e.g., essential tremor. Methods for treating patients suffering from Parkinson's disease, for example, are provided herein, including conditions such as warts and drug-induced tremors; myoclonus; chorea, e.g., drug-induced chorea; tic symptoms, e.g., drug-induced tic symptoms and organic tic symptoms; drug-induced movement disorders; drug-induced akathisia; restless legs syndrome (RLS); Stiffman syndrome; benign shivering attacks; malignant syndrome; Huntington's disease; Shy-Drager syndrome; conditions induced by brain injury, e.g., carbon monoxide or manganese poisoning; or any combination thereof.

[0230]

[0254] Generally, physicians assess the severity of Parkinson's disease in patients based on objective and subjective signs and symptoms, using various scales, for example, and prescribe levodopa medication accordingly. One well-known and widely used scale for diagnosing and quantifying the severity of Parkinson's disease is the Unified Parkinson's Disease Rating Scale (UPDRS). Modifications of the UPDRS can also be used to classify Parkinson's disease patients (e.g., the Movement Disorder Society's proposed UPDRS Part I (MDS-UPDRS Part I); the Movement Disorder Society's proposed UPDRS Part II; the Movement Disorder Society's proposed UPDRS Part III; or the Movement Disorder Society's proposed UPDRS Part IV). Parts I and II measure the effects of non-exercise and exercise experiences in daily life, and both Parts I and II are patient-reported outcomes. Part III measures exercise performance, and Part IV measures exercise complications.

[0231]

[0255] Another known method for measuring the severity of Parkinson's disease follows the Hoehn and Yahr (H&Y) scale, which includes a five-point scale. Stages 1-2 are considered to represent patients with mild or early-stage Parkinson's disease, stage 3 is considered to represent patients with moderate or mid-stage Parkinson's disease, and stages 4-5 are considered to represent patients with advanced Parkinson's disease. Additional stages 0, 1.5, and 2.5 have been added to this scale and are widely used.

[0232]

[0256] The scale for measuring changes in Parkinson's disease or its symptoms follows the Global Impression Improvement Scale (also known as the Scale of Global Impression of Change), where a score of 1 indicates no disease at all and a score of 7 indicates a very severe disease. The Global Impression of Change score is assessed by both clinicians and subjects: the Clinical Global Impression of Improvement (CGI-I) and the Subjective Global Impression of Improvement (SGI-I) (also known as the Patient Global Impression of Change (PGI-C)). It should be noted that in this field, the terms Subjective Global Impression of Change (SGI-C), Subjective Global Impression of Improvement (SGI-I), Patient Global Impression of Change (PGI-C), and Patient Global Impression of Change (PGI-I) are generally interchangeable unless understood otherwise by those skilled in the art. Similarly, the Clinician Global Impression of Change (CGI-C) and The Clinical General Impression Scale for Improvement (CGI-I) is also interchangeable unless understood otherwise by those skilled in the art. Another term known in the art is Clinical General Impression Severity (CGI-S), which can also be improved according to the methods of the present invention. Any other terms used in the art that are interchangeable are also relevant herein and covered by this disclosure. In this regard, it is noteworthy that definitions used in the art sometimes refer to “clinical” and sometimes to “clinician,” etc. These are also interchangeable in this context. For example, “Clinical General Impression Scale for Change (CGI-C)” is used interchangeably with “Clinical General Impression Scale for Change (CGI-C).” Similarly, “Clinical General Impression Scale for Improvement (CGI-I)” is used interchangeably with “Clinical General Impression Scale for Improvement (CGI-I).”

[0233]

[0257] The daily levodopa dose can be defined and changed by the physician on a case-by-case basis, depending on clinical findings and a "trial and error" approach, as well as the patient's detailed condition and response to treatment. Furthermore, patients may be administered different daily doses for different durations depending on their signs and symptoms, and the range of daily doses administered can be determined by the physician, thereby providing flexibility in treatment. It is noteworthy that physicians generally refer to signs, which are objective measures, and symptoms, which are subjective measures.

[0234]

[0258] According to several embodiments, methods for treating patients with advanced-stage Parkinson's disease are provided herein. According to several embodiments, methods for treating patients with advanced-stage and / or moderate-stage Parkinson's disease are provided herein. According to several embodiments, methods for treating patients exhibiting motor fluctuations are provided herein. According to several embodiments, methods for treating patients with Parkinson's disease exhibiting motor fluctuations are provided herein.

[0235]

[0259] According to several embodiments, methods for treating Parkinson's disease patients requiring doses of levodopa exceeding approximately 300 mg / day, 400 mg / day, 500 mg / day, 600 mg / day, 700 mg / day, 800 mg / day, 900 mg / day, or 1000 mg / day are provided herein.

[0236]

[0260] According to several embodiments, methods are provided herein for treating Parkinson's disease patients who require elevated doses of levodopa at specific times, for example, in the morning, for example, towards the end of the low-activity / nighttime period (the last hour or so), for example, at the beginning of the high-activity / daytime period (the first hour or so). For example, according to some embodiments, there may be a certain amount during the high-activity / daytime period and different amounts during the low-activity / nighttime period, and elevated doses of levodopa may be administered towards the end of the low-activity / nighttime period, at the end of the low-activity / nighttime period, at the beginning of the high-activity / daytime period, etc. Such elevated doses may be imparted, for example, by administration of an orally administered pharmaceutically acceptable oral composition at the times mentioned above, and may be imparted in combination with substantially continuous pharmaceutically acceptable liquid compositions.

[0237]

[0261] According to some embodiments, methods for treating patients suffering from Parkinson's disease for a period of time greater than about one year, greater than two years, greater than three years, greater than four years, greater than five years, greater than six years, greater than seven years, greater than eight years, greater than nine years, or greater than ten years are provided herein.

[0238]

[0262] According to several embodiments, methods are provided herein for treating patients with Parkinson's disease for at least 1 hour, at least 1.5 hours, at least 2 hours, at least 2.5 hours, and at least 3 hours of their off-time each day. According to several embodiments, methods are provided herein for treating patients with Parkinson's disease who exhibit a modified Hoehn and Yahr scale with an "on" state of ≤2, ≤2.5, ≤3, and ≤4. [Brief explanation of the drawing]

[0239] [Figure 1A]

[0263] As described in Example 1, this graph shows an increase in favorable on-time and a decrease in on-time with moderate / severe dyskinesia on days 3 and 28. [Figure 1B] As described in Example 1, this graph shows the changes from baseline in off-time (decreased), on-time without dyskinesia (increased), good on-time or on-time with no or mild dyskinesia (increased), and on-time with moderate or severe dyskinesia (decreased). [Figure 1C]

[0264] This graph shows the improved UPDRS Part III score, as described in Example 1. [Figure 2]

[0265] As described in Example 1, this graph shows the improvement in the overall patient impression of the change and the overall clinician impression of the change. [Figure 3]

[0266] This graph shows the percentage of patients reporting complete on- at 9 AM on day 7, as described in Example 1. [Figure 4]

[0267] This graph shows drug-related TEAEs reported during the first three years of continuous subcutaneous levodopa / carbidopa injections for Parkinson's disease, as described in Example 2. [Figure 5]

[0268] This graph shows the increase in on-time without problematic dyskinesia and the decrease in off-time observed at 36 months of serial subcutaneous levodopa / carbidopa injections for Parkinson's disease, as described in Example 2. Awake time was standardized to 16 hours. [Figure 6]

[0269] This diagram shows a flowchart describing how patients complete an active-controlled study with an open-label, introductory, randomized, double-blind, double-dummy comparison phase. [Figure 7]

[0270] This graph shows that treatment with ND0612 adds 1.72 hours of problematic dyskinesia-free on-time compared to immediate-release levodopa / carbidopa (IR-LD / CD; p<0.0001). [Figure 8]

[0271] This figure shows a graph illustrating the mean plasma levodopa concentration over time in units of hours after the start of subcutaneous injection, compared to five test groups. [Figure 9]

[0272] This figure shows a graph illustrating the Cmax carbidopa values ​​obtained from subcutaneous administration of three different concentrations of carbidopa. [Figure 10]

[0273] This figure shows graphs illustrating the PGI-C and CGI-I evaluations of ND0612 versus IR-LD / CD. [Figure 11]

[0274] This table shows the results from the open-label, double-blind, double-dummy study described in Example 6. [Modes for carrying out the invention]

[0240]

[0275] Features and other details of this disclosure are described in more detail below. Certain terms used herein, in the examples and in the appended claims are collected below. These definitions should be read in light of the rest of this disclosure and understood by those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art.

[0241] definition

[0276] As used herein, the term “approximately” is considered to cover a range of ±10% of the listed value(s) unless otherwise specifically mentioned or understood by those skilled in the art. It should be further noted that any value shown is considered to cover a range of ±10% of that value even without the use of the term “approximately.” This includes the values ​​in the Examples section, which may vary depending on the tools and machinery used, the purity of the compound, etc.

[0242]

[0277] As used herein, the term “combined administration” means, unless otherwise specifically mentioned or understood by those skilled in the art, the combined administration of any type of two or more active ingredients in the same composition, the simultaneous administration of such active ingredients in separate compositions, and the administration of two or more active ingredients sequentially, continuously, on the same day, or at predetermined time intervals apart from each other. The term “combined administration” may also mean the combined administration of any type of two separate pharmaceutical compositions, each composition of which may be administered via a different route, at different time intervals, in different doses, etc. For example, as detailed herein, one composition may be administered substantially continuously parenterally, for example subcutaneously, while a second composition is administered orally in combination with the first in a non-continuous manner. Furthermore, the combined administration of two or more separate compositions may be interdependent or independent.

[0243]

[0278] As used herein, the terms “continuously” and “substantially continuously” mean, unless otherwise specifically referred to or understood by those skilled in the art, periods of interruption of less than about 24 hours, about 12 hours, about 5 hours, about 3 hours, about 1 hour, about 30 minutes, about 15 minutes, about 5 minutes, or about 1 minute over the entire time between the administration of the composition. The time between the administration of the composition may be at least about 6 hours, about 8 hours, about 12 hours, about 15 hours, about 18 hours, about 21 hours, about 24 hours, 3 days, 7 days, 2 weeks, 1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, 10 years, etc.

[0244]

[0279] As used herein, the term “dopa decarboxylase inhibitor” refers to agents capable of inhibiting the peripheral metabolism of levodopa to dopamine by aromatic L-amino acid decarboxylase, such as carbidopa and benserazide.

[0245]

[0280] The terms "individual," "patient," or "subject" are used interchangeably and include any animal, including mammals, mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or non-human primates, and humans. In some embodiments, the mammal treated in the method of the present invention is a human suffering from a neurodegenerative condition, such as Parkinson's disease.

[0246]

[0281] As used herein, the term “levodopa portion” includes any portion containing levodopa, for example, levodopa itself and levodopa salts, unless otherwise specifically referred to or understood by those skilled in the art. Similarly, as used herein, the term “carbidopa portion” includes any portion containing carbidopa, for example, carbidopa itself and carbidopa salts, unless otherwise specifically referred to or understood by those skilled in the art.

[0247]

[0282] As used herein, the term “liquid” refers to any type of fluid, including gels, aqueous and non-aqueous compositions, unless otherwise specifically mentioned or understood by those skilled in the art.

[0248]

[0283] As used herein, the terms “morning dose” and “morning oral dose” are interchangeable unless otherwise specifically mentioned or understood by those skilled in the art, and refer in particular to an oral composition (e.g., oral dosage form) containing levodopa administered within the morning hours, for example, within 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, or 2 hours of the patient’s waking time. According to some embodiments, morning dose refers to an oral composition (e.g., oral dosage form) containing levodopa administered within 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, or 30 minutes of the patient’s waking time.

[0249]

[0284] Neurological disorders are disorders of the body's nervous system, and as used herein, the term “motor disorder” refers to a neurological condition that causes abnormal voluntary or involuntary movements, or slow, reduced movements. According to some embodiments, neurological disorders or motor disorders include: Parkinson’s disease; secondary parkinsonian syndromes, e.g., drug-induced secondary parkinsonian syndrome, neuroleptic-induced parkinsonian syndrome, post-encephalitis parkinsonian syndrome, and vascular parkinsonian syndrome; motor fractures; neurodegenerative disorders; dyskinesia; decreased dopamine levels in the brain; levodopa-induced dyskinesia; rapid eye movement sleep behavior disorder (RBD); dystonia; morning akinesia; Tremor symptoms, e.g., essential tremor and drug-induced tremor; myoclonus; chorea, e.g., drug-induced chorea; tic symptoms, e.g., drug-induced tic symptoms and organic tic symptoms; drug-induced motor disorders; drug-induced akathisia; restless legs syndrome (RLS); Stiffman syndrome; benign tremor attacks; neuroleptic malignant syndrome; Huntington's disease; Shy-Drager syndrome; conditions induced by brain injury, e.g., carbon monoxide or manganese poisoning; or any combination thereof. According to some embodiments, the method aims to treat Parkinson's disease and / or motor fluctuations, including motor fluctuations arising from Parkinson's disease, motor fluctuations in patients diagnosed with Parkinson's disease, etc.

[0250]

[0285] As used herein, the term “off-time” refers to a period during which a patient does not experience a response to treatment or experiences significant symptoms associated with Parkinson’s disease (e.g., motor or non-motor symptoms). In some embodiments, off-time is a recurrence of Parkinson’s disease symptoms between doses of medication.

[0251]

[0286] As used herein, the term “on time” refers to a period during which a patient experiences a good response to medication and experiences little to no symptoms associated with Parkinson’s disease (e.g., motor or non-motor symptoms). Patients may or may not experience dyskinesia during the on period.

[0252]

[0287] As used herein, the term "dyskinesia-free on-time" refers to a period during which a patient experiences on-time but does not exhibit dyskinesia (e.g., levodopa-induced dyskinesia).

[0253]

[0288] As used herein, the term “on time with non-problematic dyskinesia” refers to a period during which a patient experiences an on time and exhibits mild dyskinesia (e.g., levodopa-induced mild dyskinesia).

[0254]

[0289] The term "on-time with problematic dyskinesia" refers to a period during which a patient experiences on-time and exhibits moderate to severe dyskinesia (e.g., levodopa-induced moderate to severe dyskinesia).

[0255]

[0290] As used herein, the term "good on time" refers to the sum of on time when no dyskinesia is observed and on time when no problematic dyskinesia is observed.

[0291] Improvements, increases, decreases, etc., in any of the parameters referred to herein, including on-time, off-time, on-time without dyskinesia, on-time with insignificant dyskinesia, on-time with problematic dyskinesia, on-time with moderate to severe dyskinesia, and good on-time, are measured as therapeutic effects of the subcutaneous formulation administered according to the present invention, compared to an immediate-release formulation containing levodopa and / or from baseline, as can be understood in context or by those skilled in the art.

[0256]

[0292] As used herein, the term “baseline” is defined as the first measurement of any of the variables mentioned, taken before the application of the treatment being studied.

[0293] As used herein, the terms “third day,” “third consecutive day,” or “third consecutive day” are defined as the third consecutive day of treatment, preceded by two consecutive days of treatment.

[0257]

[0294] As used herein, the term “change from baseline” (CFB) is defined as the change in a measurement from before treatment with the treatment under study to the point in time at which it is measured. If the point in time of measurement is a specific treatment day, for example, the third day, the measurement may be taken at any time on that day unless otherwise specifically mentioned. The measurement may be taken in the morning, for example at 8 a.m., or a few hours after the patient’s waking hours.

[0258]

[0295] As used herein, the terms “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” interchangeably refer to any and all solvents, dispersions, coatings, isotonic agents, and absorption retarders, etc., that are compatible with the pharmaceutically acceptable application.

[0259]

[0296] As used herein, the terms “pharmaceutical composition” and “pharmaceutical preparation” refer to a composition or preparation comprising at least one biologically active compound, for example, levodopa or carbidopa, or a pharmaceutically acceptable salt thereof, and formulated with one or more pharmaceutically acceptable excipients.

[0260]

[0297] As used herein, the term “pharmaceutically acceptable salts” refers to salts of acidic or basic groups that may be formed with conjugates used in the compositions disclosed herein.

[0261]

[0298] As used herein, terms such as “physiologically acceptable pH value” refer to a pH value in the range of about 4.5 to about 10, unless otherwise specifically mentioned or understood by those skilled in the art. Where a pH value is given, including in the examples, the value may be in the range of about ±0.1 and / or ±10% of the listed value(s), and it should be further noted that if the measured pH is 8.1, the formulation may be prepared to obtain a pH of about 8.0 or 8.2. Such differences may be due to temperature changes, various measuring devices, etc.

[0262]

[0299] "Preventing" includes delaying the onset of clinical symptoms, complications, or biochemical signs of a condition, disorder, disease, or pathology in subjects who may suffer from or are predisposed to such a condition, disorder, disease, or pathology, but who have not yet experienced or presented any clinical or subclinical symptoms of such a condition, disorder, disease, or pathology. "Preventing" also includes prophylactic treatment of a condition, disorder, disease, or pathology, or its onset, which includes prophylactic treatment of clinical symptoms, complications, or biochemical signs of a condition, disorder, disease, or pathology, or its onset in subjects.

[0263]

[0300] In any of the embodiments provided herein, changes in values ​​(e.g., increases, decreases, or improvements) can be significant changes. As used herein, the term “significant” refers to a statistically significant change (e.g., p-value < 0.05) in a value (e.g., on time without dyskinesia, on time with non-problematic dyskinesia, on time with problematic dyskinesia, or on time with moderate to severe dyskinesia (e.g., on time without dyskinesia per day, on time with non-problematic dyskinesia per day, on time with problematic dyskinesia per day, or on time with moderate to severe dyskinesia per day)), good on time (e.g., good on time per day), off time (e.g., off time per day), subjective global impression of change (SGI-C) score, clinical global impression of change (CGI-C) score, patient global impression of change (PGI-C) score, or revised version of the Unified Parkinson's Disease Rating Scale Part II (MDS-UPDRS Part II) proposed by the Movement Disorder Society) (e.g., increase, decrease, or improvement). In one embodiment, a statistically significant change is the difference between the mean values ​​from a group of patients who received the treatment described herein (e.g., substantially continuous administration of the levodopa composition described herein over 24 hours) and the mean values ​​from a group of patients who received a control treatment (e.g., an oral levodopa composition).

[0264]

[0301] Unless otherwise specifically mentioned or understood by those skilled in the art, the terms Patient Global Impression of Change (PGI-C), Subjective Global Impression of Improvement (SGI-I), and Patient Global Impression of Improvement (PGI-I) are interchangeable. Similarly, Clinical Global Impression of Improvement (CGI-I) and Clinical Global Impression of Change (CGI-C) are interchangeable herein.

[0265]

[0302] The terms “to treat,” “treatment,” and “the act of treating” are used herein to generally refer to obtaining a desired pharmacological and / or physiological effect. The effect may be therapeutic in the sense of partially or completely curing the disease and / or adverse effects caused by the disease. As used herein, the term “treatment” covers any treatment of a disease in mammals, in particular humans, and includes (a) inhibiting the disease, i.e., preventing an increase in the severity or extent of the disease; (b) alleviating the disease, i.e., causing partial or complete improvement of the disease; or (c) preventing a relapse of the disease, i.e., preventing the disease from returning to an active state in accordance with a previously successful treatment of the symptoms of the disease or treatment of the disease.

[0266]

[0303] As used herein, the term “treatment-related adverse event” refers to an event that occurs after the administration of a certain dose (e.g., a first dose) of a treatment (e.g., a subcutaneous formulation administered according to the present invention). For example, a “treatment-related adverse event” is an event identified in a clinical trial at or after the administration of a treatment (e.g., the first dose). Examples of treatment-related adverse events (TEAEs) include, but are not limited to, drug-related TEAEs (e.g., injection site reactions). In some embodiments, treatment-related adverse events (TEAEs) are severe. In some embodiments, treatment-related adverse events (TEAEs) are serious.

[0267]

[0304] As used herein, the term “up to” is defined such that, unless otherwise specifically mentioned or understood by those skilled in the art, the range does not include “none,” “absence,” or “zero.” That is, if an ingredient is in a specific amount, for example, up to 720 mg, then 0 mg is not considered part of the range. Therefore, if a composition contains, for example, up to 360 mg, up to 370 mg, and up to 720 mg of levodopa, the composition must contain more than 0 levodopa. Similarly, if a composition contains, for example, up to 45 mg, up to 46 mg, and up to 90 mg of carbidopa, the composition must contain more than 0 carbidopa.

[0268] Treatment method

[0305] A method for treating patients with neurological or motor disorders, (a) Levodopa, levodopa salts, or any combination thereof, and (b) Dopa decarboxylase inhibitors (DDCIs), DDCI salts, or any combination thereof A method is disclosed herein that includes the step of parenterally administering a pharmaceutically acceptable liquid composition containing the above to a patient.

[0269]

[0306] Embodiments of the present invention are methods for treating patients with neurological or motor disorders, (a) Levodopa, levodopa salts, or any combination thereof, and (b) Dopa decarboxylase inhibitors (DDCIs), DDCI salts, or any combination thereof The step includes administering a pharmaceutically acceptable liquid composition containing to a patient parenterally, Two or three days after administration, the patient... Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate this.

[0270]

[0307] Embodiments of the present invention are methods for treating patients with neurological or motor disorders, (a) Levodopa, levodopa salts, or any combination thereof, and (b) Dopa decarboxylase inhibitors (DDCIs), DDCI salts, or any combination thereof The step includes administering a pharmaceutically acceptable liquid composition containing to a patient parenterally, Two or three days after administration, the patient... Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof This focuses on methods that demonstrate this.

[0271]

[0308] Embodiments of the present invention are methods for treating patients with neurological or motor disorders, (a) Levodopa, levodopa salts, or any combination thereof, and (b) Dopa decarboxylase inhibitors (DDCIs), DDCI salts, or any combination thereof The step includes administering a pharmaceutically acceptable liquid composition containing to a patient parenterally, Two or three days after administration, the patient... Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Subjective Global Impression of Change (SGI-C) score. Improvement from baseline based on the Clinical Global Impression (CGI-C) score of change, or any combination thereof This focuses on methods that demonstrate this.

[0272]

[0309] Embodiments of the present invention are methods for treating patients with neurological or motor disorders, (a) Levodopa, levodopa salts, or any combination thereof, and (b) Dopa decarboxylase inhibitors (DDCIs), DDCI salts, or any combination thereof The step includes administering a pharmaceutically acceptable liquid composition containing to a patient parenterally, Two or three days after administration, the patient... Increase from baseline in good on-time during the day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. Improvement from baseline based on the Patient Global Impression (PGI-I) score. Improvement from baseline based on the clinically holistic impression score (CGI-I), or any combination thereof This focuses on methods that demonstrate this.

[0273]

[0310] According to some embodiments, administration leads to patients showing an increase from baseline in good on-times per day. According to some embodiments, administration leads to patients showing a decrease from baseline in on-times per day in which problematic dyskinesia is observed. According to some embodiments, administration leads to patients showing improvement from baseline based on the Subjective Global Impression (SGI-C) score of change. According to some embodiments, administration leads to patients showing improvement from baseline based on the Patient Global Impression (PGI-I) score of improvement. According to some embodiments, administration leads to patients showing improvement from baseline based on the Clinical Global Impression (CGI-C) score of change. According to some embodiments, administration leads to patients showing improvement from baseline based on the Clinical Global Impression (CGI-I) score of improvement.

[0274]

[0311] Further embodiments of the present invention are methods for treating patients with neurolog...

Claims

1. A method for treating patients diagnosed with Parkinson's disease, The step includes subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa, carbidopa, and arginine to the patient substantially continuously for about 24 hours / day. The pharmaceutically acceptable liquid composition comprises about 60 mg / mL levodopa and 7.5 mg / mL carbidopa, and the pharmaceutically acceptable liquid composition is administered to deliver about 720 mg of levodopa and about 90 mg of carbidopa to the patient over a period of about 24 hours. Two or three days after administration, the patient, Increase from baseline in good on-time hours per day, Moderate to severe dyskinesia is observed, with a decrease from baseline in daily on-time. or any combination thereof A method that demonstrates at least one of the following.

2. The aforementioned increase from the baseline during good on-times of the day is an increase from the baseline of at least about 0.3 to 3.5 hours during good on-times of the day. The method according to claim 1, wherein the reduction from baseline in the on-time per day in which moderate to severe dyskinesia is observed is a reduction from baseline of at least about 0.3 to 2.5 hours in the on-time per day in which moderate to severe dyskinesia is observed.

3. The method according to claim 1, further comprising the step of administering to the patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

4. The method according to claim 1, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, the first flow rate being a high-activity flow rate during daytime hours and the second flow rate being a low-activity flow rate during nighttime hours.

5. The method according to claim 4, wherein the low-activity flow rate at night is applied for about 6 hours or about 8 hours, and the high-activity flow rate during the day is applied for about 18 hours or about 16 hours, respectively.

6. The method according to claim 4, wherein the low activity flow rate at night is approximately 0.08 mL / hour.

7. The method according to claim 4, wherein the daytime high-activity flow rate is approximately 0.64 mL / hour, approximately 0.59 mL / hour, approximately 0.55 mL / hour, approximately 0.50 mL / hour, approximately 0.45 mL / hour, approximately 0.41 mL / hour, approximately 0.36 mL / hour, or approximately 0.32 mL / hour.

8. A method for increasing good on-time in patients diagnosed with Parkinson's disease, The step includes subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of approximately 8:1 w / w to the patient substantially continuously for about 24 hours / day for about 2 to 3 consecutive days. A method wherein, by the third consecutive day, the administration results in an increase of at least approximately 0.3 to 3.5 hours from baseline in the good on time of day.

9. The method according to claim 8, wherein the administration results in an increase of approximately 1.8 hours from baseline in good on time per day.

10. The method according to claim 8, wherein the pharmaceutically acceptable liquid composition further comprises arginine.

11. The method according to claim 8, wherein the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa.

12. The method according to claim 8, wherein the pharmaceutically acceptable liquid composition is administered to the patient to deliver about 720 mg of levodopa and about 90 mg of carbidopa over a period of about 24 hours.

13. The method according to claim 8, further comprising the step of administering to the patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

14. The method according to claim 8, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, wherein the first flow rate is a high-activity flow rate during daytime hours and the second flow rate is a low-activity flow rate during nighttime hours.

15. The method according to claim 14, wherein the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours.

16. The method according to claim 14, wherein the low activity flow rate at night is approximately 0.08 mL / hour.

17. The method according to claim 14, wherein the daytime high-activity flow rate is approximately 0.64 mL / hour, approximately 0.59 mL / hour, approximately 0.55 mL / hour, approximately 0.50 mL / hour, approximately 0.45 mL / hour, approximately 0.41 mL / hour, approximately 0.36 mL / hour, or approximately 0.32 mL / hour.

18. A method for improving at least one symptom of Parkinson's disease in a patient suffering from Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w for substantially 24 hours / day, As a result of the aforementioned administration, the patient, Increased daily on-time without problematic dyskinesia, A decrease in the amount of time spent off during the day. A decrease in the revised Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, as assessed by the said UPDRS Part II score, results from improvements in daily living exercise experience. Improvement based on the Patient Global Impression (PGI-C) score of change, Improvement based on the Clinical Global Impression Index (CGI-I) score. or any combination thereof It will show at least one of the following: The improvement in the aforementioned patients was measured compared to patients treated with levodopa in immediate-release oral form. The improvements observed in the aforementioned patient are as follows: The daily on time without problematic dyskinesia increased by approximately 1.7 hours. The amount of time off per day decreased by approximately 1.4 hours. The daily activity level, as assessed by the aforementioned UPDRS Part II score, decreased by approximately 3.

0. The odds ratio for the aforementioned change in the Patient Global Impression (PGI-C) score is approximately 5.

3. The aforementioned improvement in the Clinical Global Impression Index (CGI-I) score has an odds ratio of approximately 7.2, according to the method.

19. The method according to claim 18, wherein the pharmaceutically acceptable liquid composition further comprises arginine.

20. The method according to claim 18, wherein the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa.

21. The method according to claim 18, wherein the pharmaceutically acceptable liquid composition is administered to the patient to deliver about 720 mg of levodopa and about 90 mg of carbidopa over a period of about 24 hours.

22. The method according to claim 18, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, the first flow rate being a high-activity flow rate during daytime hours and the second flow rate being a low-activity flow rate during nighttime hours.

23. The aforementioned low-activity flow rate is maintained at night for approximately 6 hours or approximately 8 hours, and the aforementioned high-activity flow rate is maintained during the day for approximately 18 hours or approximately 16 hours. The aforementioned low-activity flow rate at night is approximately 0.08 mL / hour. The method according to claim 22, wherein the daytime high-activity flow rate is approximately 0.64 mL / hour, approximately 0.59 mL / hour, approximately 0.55 mL / hour, approximately 0.50 mL / hour, approximately 0.45 mL / hour, approximately 0.41 mL / hour, approximately 0.36 mL / hour, or approximately 0.32 mL / hour.

24. A method for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of about 8:1 w / w, and further containing arginine, substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days. By the third consecutive day, the patient has received the above-mentioned treatment. An increase of at least approximately 0.3 to 3.5 from the baseline during good on-times of the day. Moderate to severe dyskinesia is observed, with a decrease of at least approximately 0.3 to 2.5 hours from baseline in daily on-time. A decrease of at least 0.1 to 2.0 from the baseline during off-hours per day. An increase of at least approximately 0.1 to 3.5 from baseline during on-hours of the day without dyskinesia. A reduction of at least 0.1 to 3.2 from baseline in the total daily incidence of problematic dyskinesia. Improvements from baseline in daily living exercise experience, as assessed by the revised Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) score, which results in a decrease of approximately 2 to 13 points from baseline, as defined by the UPDRS Part III score proposed by the Movement Disorder Society. or any combination thereof A method that demonstrates at least one of the following.

25. The method according to claim 24, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient via a device comprising a control station, reusable parts and disposable parts.

26. The method according to claim 24, wherein the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa.

27. The method according to claim 24, wherein the pharmaceutically acceptable liquid composition is administered to the patient to deliver about 720 mg of levodopa and about 90 mg of carbidopa over a period of about 24 hours.

28. The method according to claim 24, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, wherein the first flow rate is a high-activity flow rate during daytime hours and the second flow rate is a low-activity flow rate during nighttime hours.

29. The method according to claim 28, wherein the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours.

30. The method according to claim 28, wherein the low-activity flow rate at night is about 0.08 mL / hour, and the high-activity flow rate during the day is about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

31. The method according to claim 28, wherein the patient is fully awake about 5 hours after administration at the first flow rate.

32. The method according to claim 24, wherein the patient shows improvement from baseline in sleep quality two days after the procedure.

33. A method for treating a patient diagnosed with Parkinson's disease, comprising the step of subcutaneously administering a pharmaceutically acceptable liquid composition containing levodopa, carbidopa, and arginine to the patient substantially continuously for about 24 hours / day and for about 2 to 3 consecutive days, The pharmaceutically acceptable liquid composition comprises approximately 60 mg / mL levodopa and 7.5 mg / mL carbidopa. The pharmaceutically acceptable liquid composition is administered to the patient in such a manner that approximately 720 mg of levodopa and approximately 90 mg of carbidopa are delivered over a period of approximately 24 hours. By the third consecutive day, the patient has received the above-mentioned treatment. An increase of at least approximately 0.3 to 3.5 from the baseline during good on-times of the day. Moderate to severe dyskinesia is observed, with a decrease of at least approximately 0.3 to 2.5 hours from baseline in daily on-time. A decrease of at least 0.1 to 2.0 from the baseline during off-hours per day. An increase of at least approximately 0.1 to 3.5 from baseline during the daily on-time without dyskinesia. A reduction of at least 0.1 to 3.2 from baseline in the total daily incidence of problematic dyskinesia. A decrease of approximately 2 to 13 points from baseline in the UPDRS Part III score. or any combination thereof A method that demonstrates at least one of the following.

34. The method according to claim 33, further comprising the step of administering to the patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

35. The method according to claim 33, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient via a device comprising a control station, reusable parts and disposable parts.

36. The method according to claim 33, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, wherein the first flow rate is a high-activity flow rate during daytime hours and the second flow rate is a low-activity flow rate during nighttime hours.

37. The method according to claim 33, wherein the low-activity flow rate at night is applied for about 6 hours or about 8 hours, and the high-activity flow rate during the day is applied for about 18 hours or about 16 hours, respectively.

38. The method according to claim 37, wherein the low-activity flow rate at night is about 0.08 mL / hour, and the high-activity flow rate during the day is about 0.64 mL / hour, about 0.59 mL / hour, about 0.55 mL / hour, about 0.50 mL / hour, about 0.45 mL / hour, about 0.41 mL / hour, about 0.36 mL / hour, or about 0.32 mL / hour.

39. The method according to claim 37, wherein the patient is fully awake about 5 hours after administration at the first flow rate.

40. The method according to claim 33, wherein the patient shows improvement from baseline in sleep quality two days after the procedure.

41. A method for increasing good on-time in patients diagnosed with Parkinson's disease, The step includes subcutaneously administering to the patient a pharmaceutically acceptable liquid composition containing levodopa and carbidopa in a ratio of approximately 8:1 w / w, and further containing arginine, substantially continuously for about 2 to 3 consecutive days, for about 24 hours / day. A method wherein, by the third consecutive day, the administration results in an increase of at least approximately 0.3 to 3.5 hours from baseline in the good on time of day.

42. The method according to claim 41, wherein the administration results in an increase of approximately 1.8 hours from baseline in good on time per day.

43. The method according to claim 41, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient via a device comprising a control station, reusable parts and disposable parts.

44. The method according to claim 41, wherein the pharmaceutically acceptable liquid composition comprises 7.5 mg / mL carbidopa and 60 mg / mL levodopa.

45. The method according to claim 41, wherein the pharmaceutically acceptable liquid composition is administered to the patient to deliver about 720 mg of levodopa and about 90 mg of carbidopa over a period of about 24 hours.

46. The method according to claim 41, further comprising the step of administering to the patient at least one pharmaceutically acceptable oral composition comprising levodopa before or during the course of subcutaneous injection.

47. The method according to claim 41, wherein the pharmaceutically acceptable liquid composition is administered subcutaneously to the patient at a first flow rate and a second flow rate over a period of 24 hours, wherein the first flow rate is a high-activity flow rate during daytime hours and the second flow rate is a low-activity flow rate during nighttime hours.

48. The method according to claim 47, wherein the low-activity flow rate at night is applied for about 6 hours, and the high-activity flow rate during the day is applied for about 18 hours.

49. The method according to claim 47, wherein the low activity flow rate at night is approximately 0.08 mL / hour.

50. The method according to claim 47, wherein the daytime high-activity flow rate is approximately 0.64 mL / hour, approximately 0.59 mL / hour, approximately 0.55 mL / hour, approximately 0.50 mL / hour, approximately 0.45 mL / hour, approximately 0.41 mL / hour, approximately 0.36 mL / hour, or approximately 0.32 mL / hour.

51. The method according to claim 47, wherein the patient is fully turned on about five hours after administration at the first flow rate.

52. The method according to claim 41, wherein two days after the procedure, the patient shows improvement from baseline in sleep quality.

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