Solriamfetol for use in a method of treating attention deficit / hyperactivity disorder

Abstract

The present invention relates a method of treating attention deficit hyperactivity disorder (ADHD). More specifically, the present invention is directed to a method of administering a therapeutically effective amount of solriamfetol or a pharmaceutically acceptable salt thereof alone or in combination with other medications, for the treatment of attention deficit hyperactivity disorder (ADHD) in patients in need thereof.

Description

SOLRIAMFETOL FOR USE IN A METHOD OF TREATING ATTENTION DEFICIT / HYPERACTIVITY DISORDERTECHNICAL FIELD

[0001] The present invention relates to a method of treating Attention Deficit Hyperactivity Disorder (ADHD). ADHD is characterized by persistent pattern of inattention and / or hyperactivity-impulsivity that interferes with functioning or development, as characterized by a number of activities. Solriamfetol is a selective dual norepinephrine-dopamine reuptake inhibitor that promotes wakefulness in obstructive sleep apnea and narcolepsy.BACKGROUND OF THE INVENTION

[0002] Attention deficit hyperactivity disorder (ADHD) is a chronic neurobiological and developmental disorder characterized by a persistent pattern of inattention, hyperactivity, or impulsivity, that interferes with functioning or development. Impairments in cognition are apparent in attention, planning and problem solving, working memory, and behavioral inhibition. An estimated 15.5 million adults and 7 million children in the U.S. are affected by ADHD, with approximately two-thirds or more of children with ADHD continuing to experience symptoms into adulthood. The total annual societal excess cost associated with adult ADHD in the U.S. has been estimated at over $120 billion.

[0003] Solriamfetol (formerly known as JZP-110 and ADX0N006) is a dopamine and norepinephrine reuptake inhibitor (DNRI), TAAR1 agonist, and 5-HTIA agonist. Solriamfetol has a lower binding affinity to dopamine and norepinephrine transporters than other stimulants and does not promote the release of monoamines, as amphetamine stimulants do. Due to its mechanism of action as a dual reuptake inhibitor of dopamine and norepinephrine and the symptom improvement documented in patients with excessive daytime sleepiness, the present study evaluates the efficacy of solriamfetol in treating ADHD.AXSOME 43 PCTOBJECTS OF THE INVENTION

[0004] Accordingly, there is a need for the treatment of Attention Deficit Hyperactivity Disorder.SUMMARY OF THE INVENTION

[0005] The present invention is directed to a method of Attention Deficit Hyperactivity Disorder in patients comprising the administration of a therapeutically effective amount of solriamfetol or pharmaceutically acceptable salts thereof, to a mammal in need of treatment.

[0006] In another embodiment, the present invention provides a method which further comprises administering a therapeutically effective amount of at least one other therapeutic agent for the treatment of Attention Deficit Hyperactivity Disorder.

[0007] In another embodiment, the present invention provides a method wherein solriamfetol or a pharmaceutically acceptable salt thereof and the at least one other therapeutic agent for the treatment of Attention Deficit Hyperactivity Disorder are administered in the same composition.

[0008] In another embodiment, the present invention provides a pharmaceutical composition for treating Attention Deficit Hyperactivity Disorder in patients, comprising solriamfetol or a pharmaceutically acceptable salt thereof.BRIEF DESCRIPTION OF THE DRAWINGSFigure 1 shows the improvements in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score for patients treated with solriamfetol compared to patients treated with placebo.Figure 2 shows the improvements in overall ADHD disease severity, as assessed by the Clinical Global Impression of Severity (CGI-S) total score in patients treated with solriamfetol compared to patients treated with placebo.AXSOME 43 PCTDETAILED DESCRIPTION OF THE INVENTION

[0009] These and other objects of the invention will be more fully understood from the following description of the invention, the referenced drawings attached hereto and the claims appended hereto.

[0010] The present invention is directed to a method of treating Attention Deficit Hyperactivity Disorder comprising the administration of a therapeutically effective amount of solriamfetol or pharmaceutically acceptable salts thereof, to a mammal in need of treatment.Definitions

[0011] For convenience, certain terms employed in the specification, examples, and appended claims are collected here.

[0012] It is to be understood that this invention is not limited to the particular methodology, protocols, animal species or genera, and reagents described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention that will be limited only by the appended claims.

[0013] As used herein the term "subject" refers to an animal, preferably a mammal, and most preferably a human both male and female, who has been the object of treatment, observation or experiment.

[0014] The term "therapeutically effective amount" as used herein, means that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation of one or more of the signs or symptoms of the disease or disorder being treated.

[0015] The term "prophylactically effective amount" is intended to mean that amount of a pharmaceutical drug that will prevent or reduce the risk of occurrence ofAXSOME 43 PCTthe biological or medical event that is sought to be prevented of a tissue, a system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.Solriamfetol as a Pharmaceutical:

[0016] In general, solriamfetol or pharmaceutically acceptable salts thereof can be administered as pharmaceutical compositions by any method known in the art for administering therapeutic drugs including oral, buccal, topical, systemic (e.g., transdermal, intranasal, or by suppository), or parenteral (e.g., intramuscular, subcutaneous, or intravenous injection.) Administration of the compounds directly to the nervous system can include, for example, administration to intracerebral, intraventricular, intacerebroventricular, intrathecal, intracisternal, intraspinal or peri-spinal routes of administration by delivery via intracranial or intravertebral needles or catheters with or without pump devices.

[0017] Compositions can take the form of tablets, pills, capsules, semisolids, powders, sustained release formulations, solutions, suspensions, emulsions, syrups, elixirs, aerosols, or any other appropriate compositions; and comprise at least one compound of this invention in combination with at least one pharmaceutically acceptable excipient. Suitable excipients are well known to persons of ordinary skill in the art, and they, and the methods of formulating the compositions, can be found in such standard references as Alfonso AR: Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton PA, 1985, the disclosure of which is incorporated herein by reference in its entirety and for all purposes. Suitable liquid carriers, especially for injectable solutions, include water, aqueous saline solution, aqueous dextrose solution, and glycols.Dosage Regimens

[0018] The present invention provides methods of providing Attention Deficit Hyperactivity Disorder treatment in a mammal using Solriamfetol or pharmaceutically acceptable salts thereof. The amount of the solriamfetol compound necessary toAXSOME 43 PCTreduce or treat Attention Deficit Hyperactivity Disorder is defined as a therapeutically or a pharmaceutically effective dose. The dosage schedule and amounts effective for this use, i.e., the dosing or dosage regimen will depend on a variety of factors including the stage of the disease, the patient's physical status, age and the like. In calculating the dosage regimen for a patient, the mode of administration is also taken into account.

[0019] A person of ordinary skill in the art will be able without undue experimentation, having regard to that skill and this disclosure, to determine a therapeutically effective amount of Solriamfetol or pharmaceutically acceptable salts thereof for practice of this invention (see, e.g., Lieberman, Pharmaceutical Dosage Forms (Vols. 1-3, 1992); Lloyd, 1999, The art, Science and Technology of Pharmaceutical Compounding; and Pickar, 1999, Dosage Calculations). A therapeutically effective dose is also one in which any toxic or detrimental side effects of the active agent that is outweighed in clinical terms by therapeutically beneficial effects. It is to be further noted that for each particular subject, specific dosage regimens should be evaluated and adjusted over time according to the individual need and professional judgment of the person administering or supervising the administration of the compounds.EXAMPLE

[0020] The following example illustrates the invention without limiting its scope.Example 1

[0021] FOCUS (Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, 6-week, parallel group trial to evaluate the efficacy and safety of solriamfetol in adults with ADHD in the United States. A total of 516 adult patients with a primary diagnosis of ADHD are randomized 1:1:1 to treatment with solriamfetol 150 mg, solriamfetol 300 mg, or placebo, once daily for 6 weeks. The primary endpoint is the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6. Total scores on the AISRSAXSOME 43 PCTrange from 0 to 54, with 0 corresponding to total absence of symptoms and higher scores corresponding to greater symptom severity. Mean baseline AISRS total scores for the solriamfetol 150 mg, solriamfetol 300 mg, and placebo groups are 39.1, 38.3, and 37.9 respectively. The key secondary endpoint is the change from baseline in the Clinical Global Impression of Severity (CGI-S) for ADHD at Week 6.

[0022] The FOCUS Phase 3 trial of solriamfetol in the treatment of attention deficit hyperactivity disorder (ADHD) achieved its primary and key secondary endpoints demonstrating statistically significant improvements in ADHD symptoms and disease severity with solriamfetol compared to placebo. The FOCUS study is a randomized, double-blind, placebo-controlled, multicenter, U.S. trial, in which 516 adults with ADHD are randomized to receive solriamfetol 150 mg, solriamfetol 300 mg, or placebo, once daily, for 6 weeks.

[0023] The study achieved the primary endpoint by demonstrating a statistically significant reduction in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score compared to placebo at Week 6, with mean reductions from baseline of 17.7 points for solriamfetol 150 mg and 14.3 points for placebo (p=0.039). Overall, the improvement with solriamfetol at Week 6 represents a 45% mean reduction from baseline in ADHD symptoms. Improvements in the AISRS total score were greater with solriamfetol compared to placebo starting at Week 1 (p=0.036). Clinical response, defined as >30% improvement from baseline in the AISRS total score, was achieved by a statistically significantly greater percentage of patients treated with solriamfetol 150 mg (53.5%) compared to those treated with placebo (41.3%) at Week 6 (p=0.024). The primary endpoint data are shown in Figure 1.

[0024] The study also achieved the key secondary endpoint by statistically significantly reducing overall ADHD disease severity compared to placebo, as assessed by the Clinical Global Impression of Severity (CGI-S) for ADHD, at Week 6 (p=0.017). The secondary endpoint data are shown in Figure 2.

[0025] Results on the primary and key secondary endpoints for the exploratory 300 mg solriamfetol dose were numerically superior compared to placebo but were not statistically significant.AXSOME 43 PCT

[0026] ADHD substantially impairs social, academic, and occupational functioning, while negatively impacting patient quality of life and increasing the risk of morbidity and mortality. The results of the FOCUS trial demonstrate that solriamfetol was able to reduce mean ADHD symptom burden by nearly fifty percent, which contributed to significant reductions in disease severity. These results are especially promising as part of a comprehensive wellness plan for individuals with ADHD. The symptom improvements observed with solriamfetol were accompanied by a favorable safety and tolerability profile. Based on these compelling data, solriamfetol has the potential to be an important new treatment option for adult patients living with ADHD.

[0027] The present invention is not to be limited in terms of the particular embodiments described in this application, which are intended as single illustrations of individual aspects of the invention. Many modifications and variations of this invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatus within the scope of the invention, in addition to those enumerated herein will be apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications and variations are intended to fall within the scope of the appended claims. The present invention is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled.References cited

[0028] All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

[0029] The discussion of references herein is intended merely to summarize the assertions made by their authors and no admission is made that any reference constitutes prior art. Applicants reserve the right to challenge the accuracy and pertinence of the cited references.AXSOME 43 PCT

[0030] All patents, applications, publications, test methods, literature, and other materials cited herein are hereby incorporated by reference.AXSOME 43 PCT

Claims

CLAIMS:

1. A method of treating attention deficit hyperactivity disorder (ADHD) in patients in need thereof, comprising administering a therapeutically effective amount of solriamfetol or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the method further comprises administering a therapeutically effective amount of at least one other therapeutic agent for the treatment of attention deficit hyperactivity disorder (ADHD).

3. The method of claim 1 , wherein solriamfetol or a pharmaceutically acceptable salt thereof and the at least one other therapeutic agent for the treatment of attention deficit hyperactivity disorder (ADHD) are administered in the same composition.

4. A pharmaceutical composition for treating attention deficit hyperactivity disorder (ADHD) in patients in need thereof, comprising solriamfetol ora pharmaceutically acceptable salt thereof.

5. A method or pharmaceutical composition substantially as shown and described in the preceding claims.AXSOME 43 PCT

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