Administration of tasimelteon under fasted conditions

Abstract

To provide methods for administering tasimelteon to a human patient comprising orally administering an effective amount of tasimelteon under fasted conditions.SOLUTION: One embodiment of the invention provides a method for administering tasimelteon to a human patient, comprising orally administering an effective dose of tasimelteon under fasted conditions. Fasted conditions may comprise administering the tasimelteon without food, no food at least 1 / 2 hour prior to administration, no food at least 1 hour prior to administration, no food at least 1.5 hours prior to administration, no food at least 2 hours prior to administration, no food at least 2.5 hours prior to administration, or no food at least 3 hours prior to administration. Tasimelteon may be administered, for example, at a dose of 20 mg / day. Tasimelteon may be administered when, for example, the patient is being treated for a circadian rhythm disorder or for a sleep disorder, including, for example, Non-24 Disorder.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 61 / 927,465, filed January 14, 2014, and U.S. Patent Application No. 14 / 511,669, filed October 10, 2014, which are hereby incorporated by reference as if fully set forth herein. [Background technology]

[0002] Tasimelteon and methods of using and processes for making tasimelteon are disclosed in various references, including U.S. Pat. No. 5,856,529, U.S. Patent Application Publication No. 20090105333, and U.S. Patent Application Publication No. 20130197076, copies of which are attached hereto and incorporated by reference herein as if fully set forth herein. Summary of the Invention [Means for solving the problem]

[0003] One embodiment of the present invention provides a method for administering tasimelteon to a human patient, comprising orally administering an effective dose of tasimelteon under fasting conditions. Fasting conditions may include administering tasimelteon without food, without food for at least ½ hour, without food for at least 1 hour, without food for at least 1.5 hours, without food for at least 2 hours, without food for at least 2.5 hours, or without food for at least 3 hours. According to such an embodiment, tasimelteon may be administered at a dose of, for example, 20 mg / day. Tasimelteon may be administered, for example, when a patient is being treated for a circadian rhythm disorder or sleep disorder, including, for example, a non-24-hour disorder.

[0004] Another embodiment of the invention provides a method of administering tasimelteon to a human patient, comprising instructing the patient to take the tasimelteon without food.

[0005] Yet another embodiment of the present invention is directed to the determination of T in human patients treated with tasimelteon. max The present invention provides a method for reducing urinary tract infection (UUID) by orally administering an effective dose of tasimelteon under fasting conditions.

[0006] In yet another embodiment, the present invention provides a method of marketing or selling tasimelteon, comprising informing a dispenser, patient, and / or insurer that tasimelteon should be taken under fasting conditions, e.g., by including such instructions in printed prescribing information packaged with a container containing tasimelteon capsules. DETAILED DESCRIPTION OF THE INVENTION

[0007] The present invention relates to administering tasimelteon under fasting conditions, ie, without food.

[0008] A clinical study was conducted to investigate the effect of food on the administration of tasimelteon. Specifically, the primary objective of this study was to investigate the effect of food (high calorie / high fat) on the pharmacokinetics of 100 mg of tasimelteon in healthy subjects. This was a single-center, open-label, crossover design lasting up to 5 weeks. Twenty-six healthy male and female subjects (aged 18-50 years) were enrolled in this study. It was a two-period, randomized, two-sequence crossover design in which each subject received 100 mg of tasimelteon either with or without food. Subjects were randomly assigned to receive 100 mg of tasimelteon capsules under fasting conditions or 100 mg of tasimelteon under fed conditions (i.e., 30 minutes after the start of ingestion of a high-fat meal). There was a 7-day washout period between treatment groups. Figure 1 shows an example of the overall study design. In this figure, tasimelteon is referred to as VEC-162.

[0009] [ka]

[0010] For the purposes of this study, fasting administration was performed with 240 mL of water at approximately 6:00 AM after at least 10 hours of fasting. Subjects were not permitted to consume any food for at least 4 hours after dosing. Subjects were allowed to drink water as desired, except 1 hour before and 2 hours after drug administration.

[0011] Under fed conditions, the drug was administered with 240 mL of water at approximately 6:00 AM after a high-fat / high-calorie breakfast containing one cup of milk. Subjects began the recommended meal 30 minutes before drug administration. Subjects completed the meal within 30 minutes, and the drug was administered approximately 30 minutes after the start of the meal. Subjects were not permitted to consume any food for at least 4 hours after dosing. Subjects were allowed to drink water as desired, except 1 hour before and 2 hours after drug administration.

[0012] Twenty-five subjects completed both periods of the study. Administration of tasimelteon with a high-fat / high-calorie meal resulted in a lower C max and longer T max Under fasting conditions, the mean C of 786 + / - 432 ng / mL was obtained. max The mean C value was 445 + / - 255 ng / mL with a geometric mean rate of 55.82% and an associated 90% confidence interval of 49.72% to 62.67%. max The AUC (0-t) and AUC (Inf) Absorption, as measured by C, was comparable under both fed and fasted conditions, with geometric mean rates of 108.57% and 106.54%, respectively, and 90% confidence intervals contained within an equivalence window of 80% to 125%. max The median T max increased from 0.75 h under fasted conditions to 2.5 h under fed conditions.

[0013] This study concluded that administration of tasimelteon with a high-fat / high-calorie meal resulted in a significant decrease in the rate of absorption, but no significant change in the amount absorbed.

[0014] Thus, in an illustrative embodiment, the present invention provides a method of administering tasimelteon to a human patient, comprising orally administering an effective dose of tasimelteon under fasting conditions; A method of administering tasimelteon to a human patient, comprising instructing the patient that tasimelteon should be administered without food; T in human patients treated with tasimelteon max a method for reducing the risk of rheumatoid arthritis, said method comprising orally administering an effective dose of tasimelteon under fasting conditions; This includes methods of marketing or selling tasimelteon, which include informing pharmacists, patients, and / or insurers that tasimelteon should be taken under fasting conditions, for example, by including such instructions in printed prescribing information packaged with a container containing tasimelteon capsules.

[0015] In a specific illustrative embodiment, the fasting condition comprises administering tasimelteon without food; Fasting conditions include abstaining from food for at least 1 / 2 hour prior to administration; fasting conditions include abstaining from food for at least 1 hour prior to administration; Fasting conditions included abstaining from food for at least 1.5 hours prior to dosing; Fasting conditions included abstaining from food for at least 2 hours prior to dosing; fasting conditions include abstaining from food for at least 2.5 hours prior to dosing; or Fasting conditions involve abstaining from food for 3 hours prior to dosing.

[0016] In another illustrative embodiment, the Cmax is reduced while the AUC is approximately the same regardless of whether the drug is administered under fed or fasted conditions; The dose of tasimelteon was 20 mg / day. The patient is being treated for a circadian rhythm disorder or sleep disorder, and / or Patients are treated for non-24-hour disorders.

[0017] Specific examples of statements that may be included in prescription information (i.e., "labeling") include, for example: "Peak concentration of tasimelteon (T max ) occurs approximately 0.5 to 3 hours after fasted oral administration. When administered with a high-fat meal, the C max was 44% lower than when given in the fasted state, and median T max was delayed by approximately 1.75 hours. Therefore, HETLIOZ should be taken without food. Examples include: <Additional Notes> Aspects of the present disclosure include the following. <Section 1> A method of administering tasimelteon to a human patient comprising orally administering an effective dose of tasimelteon under fasting conditions. <Section 2> the fasting condition comprises administering tasimelteon without food; the fasting conditions include abstaining from food for at least ½ hour prior to administration; the fasting conditions include abstaining from food for at least one hour prior to administration; the fasting conditions include abstaining from food for at least 1.5 hours prior to administration; the fasting conditions include abstaining from food for at least 2 hours prior to administration; the fasting conditions include abstaining from food for at least 2.5 hours prior to administration; or the fasting conditions include abstaining from food for 3 hours prior to administration; The method described in <Item 1>. <Section 3> The method according to <Item 1>, wherein the Cmax of the tasimelteon is reduced while the AUC of the tasimelteon is kept approximately the same, regardless of whether the tasimelteon is administered under fed or fasted conditions. <Section 4> The method according to <Item 1>, wherein the effective dose of tasimelteon is 20 mg / day. <Section 5> The method according to <Item 1>, wherein the effective dose is effective for treating a circadian rhythm disorder or a sleep disorder. <Section 6> The method according to <Item 1>, wherein the effective dose is effective for treating a non-24-hour disorder. <Section 7> A method of administering tasimelteon to a human patient, comprising instructing the patient to take the tasimelteon without food. <Section 8> Taking tasimelteon without food includes taking tasimelteon without food; Taking tasimelteon without food includes abstaining from food for at least 1 / 2 hour before administration; Taking tasimelteon without food includes abstaining from food for at least 1 hour before administration; Taking tasimelteon without food includes abstaining from food for at least 1.5 hours before administration; Taking tasimelteon without food includes abstaining from food for at least 2 hours before administration; Taking tasimelteon without food includes abstaining from food for at least 2.5 hours before administration; or Taking tasimelteon without food involves abstaining from food for 3 hours before administration. The method described in <Item 7>. <Section 9> T in human patients treated with tasimelteon max 10. A method for reducing GI proficiency, said method comprising orally administering an effective dose of tasimelteon under fasting conditions. <Section 10> the fasting condition comprises administering tasimelteon without food; the fasting conditions include abstaining from food for at least ½ hour prior to administration; the fasting conditions include abstaining from food for at least one hour prior to administration; the fasting conditions include abstaining from food for at least 1 hour to 1 / 2 hour prior to administration; the fasting conditions include abstaining from food for at least 2 hours prior to administration; the fasting conditions include abstaining from food for at least 2 to 1 / 2 hours prior to administration; or the fasting conditions include abstaining from food for 3 hours prior to administration; The method described in <Item 9>. <Section 11> The method according to <Item 9>, wherein the Cmax of the tasimelteon is reduced while the AUC of the tasimelteon is kept approximately the same, regardless of whether the tasimelteon is administered under fed or fasted conditions. <Section 12> The method according to <Item 9>, wherein the effective dose of tasimelteon is 20 mg / day. <Section 13> The method according to <Item 9>, wherein the effective dose is effective for treating a circadian rhythm disorder or a sleep disorder. <Section 14> The method according to <Item 9>, wherein the effective dose is effective for treating a non-24-hour disorder.

Claims

[Claim 1] 1. A pharmaceutical composition comprising tasimelteon for use in treating a non-24-hour circadian rhythm disorder, the treatment comprising orally administering 20 mg / day of tasimelteon to a human patient without food and withholding food for at least ½ hour before administration of tasimelteon; The treatment reduces the T of tasimelteon compared to administering tasimelteon with food. ｍａｘ A pharmaceutical composition effective in shortening

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