Treatment of disorders with tasimelteon

Abstract

To provide methods to improve sleep in individuals experiencing an advance in established bedtime.SOLUTION: A method of treating an individual experiencing a sleep-wake-cycle-disrupting advance in the individual's established bedtime comprises administering to the individual an amount of tasimelteon effective to reduce one or more untoward consequences of the resulting disruption of the individual's established sleep-wake cycle.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Cross-references to related cases This application claims the benefit of co-pending U.S. Provisional Patent Application Nos. 62 / 638,212, filed March 4, 2018, and 62 / 675,687, filed May 23, 2018, each of which is incorporated herein by reference as if fully set forth. [Background technology]

[0002] The present invention relates to the clinical use of tasimelteon to treat disorders, particularly disorders caused by a sudden advance in circadian rhythm as a result of a change in an individual's usual bedtime. Such a change in usual bedtime may result from the need to adjust to a new sunrise-sunset cycle (e.g., travel through multiple time zones necessitating a rapid adjustment to a new local time at the destination), or from the need to adjust to an earlier bedtime, such as in the case of a "shift change" where a day worker begins a night shift (e.g., a worker's usual start time in their time zone changes from 8:00 AM to midnight, resulting in an earlier bedtime from 11:00 PM to 3:00 PM).

[0003] This disorder, a result of the sudden circadian advance caused by traveling through multiple time zones, is commonly referred to as "jet lag disorder" or "JLD" and is typically characterized by nighttime insomnia and decreased daytime alertness. JLD, along with disruptions to social and occupational functioning, affects millions of people annually, and symptoms are often more severe with eastward travel. Globally, an estimated 100 million people travel through five or more time zones each year.

[0004] Tasimelteon (also known as MA-1 or HETLIOZ®), as well as its pharmaceutical compositions and methods of use, have been described in the art. Tasimelteon is approved for human use for the treatment of non-24-hour sleep-wake disorder (Non-24). It is available in a 20 mg unit dosage form (capsules) and is indicated for administration at the same time each night before bedtime. Pharmacologically, tasimelteon is an agonist of the MT1R and MT2R melatonin receptors in the suprachiasmatic nucleus (SCN), a brain region involved in the biological clock. Engagement of these receptors by melatonin is thought to regulate circadian rhythms, including the sleep-wake cycle. Consistent with melatonin's receptor binding profile, tasimelteon exhibits potent circadian clock-regulating activity in preclinical models of acute phase shifts and long-term reentrainment.

[0005] Tasimelteon itself is described in claim 7 of U.S. Patent No. 5,856,529. U.S. Patent No. 5,856,529 also contains other claims, including a claim directed to a class of compounds that includes tasimelteon as a member, as well as a claim directed to the use of this class of compounds in treating sleep disorders and circadian rhythm disorders in patients by administering an effective amount of tasimelteon. The patent describes tasimelteon as a melatonin agonist and further speculates that melatonin agonists may be useful in further studying melatonin receptor interactions and in treating conditions affected by melatonin activity. The patent lists depression, jet lag, work-shift syndrome, and sleep disorders, among other potential therapeutic uses. Elsewhere in the patent, compounds within the class of compounds that includes tasimelteon as a member are disclosed as being useful as melatonin agonists in the treatment of sleep disorders, seasonal depression, circadian rhythm alterations, depression, stress, appetite control, benign prostatic hyperplasia, and related conditions. is shown.

[0006] In addition to the approved daily dose of 20 mg of tasimelteon at the same time each day before bedtime, WO 2007 / 137244 reports the discovery that the effective human dose of tasimelteon may range from 10 to 100 mg / day for potential use in sleep disorders and circadian rhythm disorders, and further states that the exact dose may depend on the particle size of tasimelteon and the size of the patient being treated. The patent also describes a 20 mg oral unit dosage form of tasimelteon, as well as clinical trials using daily doses of tasimelteon of 10 mg, 20 mg, 50 mg, and 100 mg.

[0007] U.S. Patent Application Publication No. 2009 / 0105333(A1) (WO 2007 / 137244) reports the results of the aforementioned clinical trial testing tasimelteon in subjects with a 5-hour advanced sleep-wake cycle (i.e., subjects with an advanced sleep-wake cycle of the type that a subject traveling across the Atlantic from New York to London on a jet plane might experience), including a report that treatment produced positive results in changes in twilight melatonin secretion onset time and sleep efficiency compared to placebo. The description of this trial and its reported results is incorporated herein by reference as if fully set forth. Summary of the Invention

[0008] The present invention particularly includes methods of treating an individual experiencing a sleep-wake-cycle-disrupting advance of the individual's default or usual bedtime, comprising administering to the individual an amount of tasimelteon effective to reduce one or more untoward consequences of the resulting disruption of the individual's default sleep-wake cycle. Accordingly, the present invention includes advancing an individual's default bedtime by up to 9 hours, although advances of up to 8 hours (e.g., 6-8 hours) may result in similar disruptions. DETAILED DESCRIPTION OF THE INVENTION

[0009] The usual dosage of tasimelteon is 20 mg per day. Ideally, the immediate-release form of tasimelteon is administered for at least three consecutive days to treat these conditions. For example, a disruption that causes an individual to advance their usual bedtime by eight hours can be treated by administering tasimelteon for five consecutive days.

[0010] Tasimelteon is optimally administered before bedtime, i.e., close to the individual's bedtime. Tasimelteon is typically administered 30 minutes to 1 hour before bedtime, but alternatively, it may be administered up to 2 hours before bedtime. When treating the above-described advances, the first of at least three doses is administered before the first bedtime after the advance that disrupts the sleep-wake cycle.

[0011] When tasimelteon is administered according to the above-described dosing regimen, the reduction in adverse effects includes an improvement in at least one sleep parameter selected from the group consisting of total sleep time, latency to persistent sleep, and wake after sleep onset, e.g., an improvement in total sleep time, specifically in the first two-thirds of the night on the third day after tasimelteon administration, or an improvement in next-day alertness, which may be measured as an improvement on the Karolinska Sleepiness Scale, an improvement on the visual analog scale, or both.

[0012] Therefore, the present invention provides a method for preventing and treating a patient's condition in which the individual's normal bedtime advance is within 9 hours (e.g., 6 to 8 hours), and the dosage of tasimelteon is 20 mg per day, and at least The present invention also includes treating an individual with tasimelteon administered before bedtime for three consecutive days, with the first dose administered in immediate-release form before the first bedtime after an advance that disrupts the sleep-wake cycle. In this regard, one embodiment of the present method treats an individual experiencing an advance that disrupts the sleep-wake cycle as a result of traveling on an eastbound jet. For example, such an individual may experience a significant improvement in total sleep time on both subjective and objective sleep measures in the first two-thirds of the night after administering the third dose of tasimelteon.

[0013] Another aspect of the present invention is to treat an individual who is known from their medical history to have previously experienced a process that disrupts their sleep-wake cycle and is therefore known to be in need of treatment to reduce one or more adverse effects of subsequent disruption of their normal sleep-wake cycle. For example, an individual may be known to experience adverse effects of disruption of their normal sleep-wake cycle from eastbound jet travel.

[0014] One embodiment of the method occurs when a sleep-wake cycle-disrupting advance occurs upon arrival after an eastbound jet flight to a destination that is within 8 hours (e.g., 6-8 hours) of the flight's departure time. Specifically, the invention includes treating an individual whose history of sleep-wake cycle-disrupting advances indicates a need for treatment to reduce one or more adverse effects of the individual's subsequent sleep-wake cycle disruption. Thus, according to the method, 20 mg of tasimelteon per day in immediate-release form is administered to such an individual within 1 hour of bedtime for at least three consecutive days, with the first dose administered prior to the first bedtime after the sleep-wake cycle-disrupting advance.

[0015] One aspect of the present invention is the treatment of individuals experiencing at least one night of insomnia after experiencing a 6-8 hour bedtime advance, such as at least one awakening during the night for a normal, non-advanced individual, such as upon arrival in London after an overnight flight from the East or West Coast of the United States.

[0016] One specific embodiment of the present invention includes a method for treating jet lag in an individual who has experienced eastward travel from a departure location through six to eight time zones during overnight airplane travel (e.g., eight time zones as would be experienced on an eastward flight from San Francisco to London) to a destination location, comprising orally administering to the individual, after arrival at the destination, a 20 mg immediate-release form of tasimelteon at or before the individual's bedtime at the destination. Such methods include administration 30 minutes to 2 hours before the individual's bedtime (i.e., local time) that corresponds to the individual's usual bedtime at the departure location (e.g., at or within 30 minutes, 60 minutes, 90 minutes, or 120 minutes of such bedtime), and include administration to individuals who have been pre-selected for tasimelteon administration based on having experienced jet lag as a result of a previous similar travel experience, and who are treated with once-daily tasimelteon administration for at least three consecutive days (e.g., not more than five consecutive days).

[0017] Another aspect of the present invention provides a method of treating an individual whose sleep-wake cycle is disrupted by an advance of 8 hours or less at the individual's usual bedtime, comprising administering 20 mg of tasimelteon per day to the individual up to 1 hour before the individual's advanced (i.e., local time) bedtime for at least 3 consecutive days, with the first dose administered before the first bedtime after the advance that disrupts the sleep-wake cycle.

[0018] Thus, the present invention provides a method for preventing and treating an individual's inflammatory bowel disease by administering 20 mg of tasimelteon in an immediate release dosage form to said individual prior to said individual's advanced bedtime for at least three consecutive days. This may include reducing the adverse effects of an advance of up to 9 hours (e.g., 6 to 8 hours) in a person's usual bedtime, or treating an individual experiencing an advance that disrupts the sleep-wake cycle within 8 hours of the individual's usual bedtime, wherein the first dose is administered before the first advanced bedtime.

[0019] As used herein, in the context of sleep-wake cycle disruption advances caused by eastward jet travel, an individual's "advanced bedtime" refers to the individual's usual or default bedtime in the new eastern location. For example, an individual whose usual bedtime in Los Angeles is 10:00 PM would have an "advanced bedtime" of 10:00 PM in London.

[0020] Generally, the present invention relates to sleep-wake cycle disruptive advances in an individual's default sleep-wake cycle, which occur when an individual's normal or default bedtime is suddenly advanced to an earlier time (relative to the individual's default 24-hour clock) sufficiently that the individual experiences one or more of the known effects of such a disruption to the individual's sleep-wake cycle.

[0021] For example, during a jet flight from San Francisco to London, an individual arriving in London will experience an approximately 8-hour advance in their normal sleep-wake cycle, given that they will travel through eight time zones. Similarly, any advance in an individual's normal bedtime is known to have adverse effects resulting from such disruptions to the sleep-wake cycle. Such an advance will occur during the in-transit period (e.g., 10-13 hours).

[0022] Amounts of tasimelteon effective in the above methods are known in the art from previously reported clinical studies of tasimelteon. For example, a 20 mg capsule of tasimelteon is useful in the above methods and can be administered at an individual's advanced bedtime or, preferably, before that bedtime (e.g., 30 minutes to 2 hours before advanced bedtime).

[0023] The reduction in adverse effects resulting from processes that disrupt the sleep-wake cycle may be determined by an individual's response to treatment, such as improved sleep parameters (such as improved total sleep time, improved sleep time in the first two-thirds of the night, increased rapid eye movement (REM) sleep, and / or reduced time to 30 minutes of total REM sleep) compared to what the individual would have experienced in the absence of tasimelteon treatment.

[0024] Direct measures of improvement include improvement in next-day alertness, which can be measured using established tools, such as improvement on the Karolinska Sleepiness Scale or Visual Analogue Scale, or both.

[0025] Finally, the invention herein includes packaged dosage units containing a plurality of individual tasimelteon unit doses (e.g., tablets) (each containing 20 mg of tasimelteon) sufficient to provide a course of treatment to an individual being treated for jet lag disorder, for example, packaged dosage units containing 3 to 5 20 mg immediate-release tasimelteon tablets per individual dosage unit. Such dosage units can contain any conventional pharmaceutical container for the dispensed medication. Particular preferred dosage units are 3-unit-dose or 5-unit-dose blister packs. [Example]

[0026] Aspects of the present invention are more fully understood based on the clinical trial results described in Examples 1 and 2, as set forth below.

[0027] Example 1 A Phase III clinical trial of 318 healthy volunteers demonstrated the efficacy of tasimelteon in treating jet lag. During the trial, volunteers underwent a circadian stress of advancing their usual bedtime by 8 hours, consistent with the stress experienced by those traveling through eight time zones (e.g., from Los Angeles to London or from Washington, DC, to Moscow) that typically contributes to jet lag.

[0028] The results of this study demonstrate that the 20 mg dose of tasimelteon has a highly significant and clinically meaningful effect on the study's primary endpoint as well as several secondary endpoints. The prespecified primary endpoint used for this purpose was the amount of sleep time in the first two-thirds of the night. Secondary endpoints included measures of various sleep parameters (i.e., total sleep time (TST), latency to persistent sleep (LPS), and wake after onset (WASO)), as well as next-day alertness as measured using the Karolinska Sleepiness Scale (KSS) and visual analog scale (VAS). A summary of the results of the primary and secondary endpoints is provided in Table 1 below.

[0029] [Table 1]

[0030] These results demonstrate the efficacy of tasimelteon in treating jet lag. The 85-minute improvement in total sleep time versus placebo is a highly clinically meaningful benefit. Next-day alertness measures on both the KSS and VAS scales were also significant, highlighting tasimelteon's ability to address both nighttime and daytime jet lag symptoms.

[0031] Tasimelteon was also shown to significantly increase total rapid eye movement (REM) sleep time while significantly decreasing the time required to accumulate 30 minutes of REM sleep. These results are shown in Table 2 below.

[0032] [Table 2]

[0033] Thus, tasimelteon demonstrated a significant improvement in the accumulation of REM sleep, which is tightly regulated by the circadian pacemaker, during an 8-hour phase advance in sleep timing. These results suggest that tasimelteon increases sleep duration during circadian timing disorders, at least in part, by affecting the circadian pacemaker, further supporting tasimelteon as a circadian rhythm modulator for the treatment of JLD.

[0034] Example 2 This biphasic transatlantic travel study, consisting of 25 subjects (tasimelteon: n=13, placebo: n=12), included an observational travel study, Phase 1, to collect baseline data, and a treatment phase, Phase 2. Participants traveled across five or eight time zones, either from Washington, DC, to London (five time zones) or from San Francisco or Los Angeles to London (eight time zones). Participants stayed at each destination for three nights and four days, receiving 20 mg of tasimelteon before bedtime for three consecutive days during randomization. Efficacy was monitored by polysomnography (PSG) and sleep-wake questionnaire scales. During the baseline phase, sleep was most disrupted on the third night, as shown in Table 3 below.

[0035] [Table 3]

[0036] The primary endpoint of the study was the first two-thirds of the night, when sleep is most likely to be disrupted. From Table 2, these are the TSTs for night 3, followed by nights 1 and 2.

[0037] Table 4 below shows the TST for the third night. 2 / 3 and TST フル , as well as the effects of tasimelteon and placebo on measures of sleep quality, sleep latency, and WASO.

[0038] [Table 4]

[0039] As can be seen from Table 4, tasimelteon significantly improves both objective and subjective measures of sleep. Patients treated with tasimelteon slept 76 minutes longer in the first two-thirds of the third night of the treatment trip, and 131 minutes longer in total in the first two-thirds of all three nights, compared to the baseline observation trip.

[0040] Subjective measures of TST, sleep quality, sleep latency, and WASO, determined using the Post-Sleep Questionnaire (PSQ), show similar improvements among participants treated with tasimelteon. Measures of global function, including the Patient Global Impression of Severity (PGI-S) and KSS, also favor tasimelteon.

[0041] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. As used herein, the terms "comprises" and / or "comprising" declare the presence of stated features, integers, steps, operations, elements, and / or components, but may also include one or more other features, integers, steps, operations, elements, components, and / or components thereof. It should further be understood that the presence or addition of groups is not precluded. "Desired" or "desirably" means that the subsequently described event or circumstance may or may not occur, and that examples where the event occurs and examples where it does not occur are included in the description.

[0042] Structure, material, acts, and equivalents corresponding to all means, step, and function elements in the following claims are intended to include all such structure, material, or acts for performing that function in combination with other specifically claimed elements. The description of the present disclosure has been presented for purposes of illustration and description and is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. Many modifications and variations will become apparent to those skilled in the art without departing from the scope and spirit of the present disclosure. Any embodiments selected and described herein are intended to best explain the principles and practical applications of the disclosure and to enable those skilled in the art to understand the disclosure for various embodiments with various modifications to suit the particular use contemplated. The present invention includes the following aspects. <1> A method for treating an individual experiencing a condition that disrupts the individual's sleep-wake cycle at the individual's usual bedtime, comprising administering to the individual an amount of tasimelteon effective to reduce one or more adverse effects of the resulting disruption of the individual's usual sleep-wake cycle. <2> The individual's default bedtime advance was an 8-hour advance caused by eastbound jet travel; <1> The method described below. <3> The dose of tasimelteon is 20 mg per day administered in an immediate-release form before bedtime for at least three consecutive days, with the first dose administered before the first bedtime after an advance that disrupts the sleep-wake cycle. <2> The method described below. <4> The reduction in adverse effects is an improvement in at least one sleep parameter selected from the group consisting of total sleep time, latency to sleep, and wake-after-sleep time. <3> The method described below. <5> The improved sleep parameter was total sleep time. <4> The method described below. <6> On the third night after tasimelteon administration, total sleep time during the first two-thirds of the night improved. <5> The method described below. <7> The reduction in adverse effects is an improvement in next-day alertness. <3> The method described below. <8> The improvement in next-day alertness includes an improvement in the Karolinska Sleepiness Scale, an improvement in the visual analog scale, or both. <7> The method described below. <9> the individual's default bedtime advance is 6 to 8 hours, the dose of tasimelteon is 20 mg per day administered in an immediate-release form before bedtime for 3 consecutive days, and the first dose is administered before the first bedtime after the sleep-wake cycle disruption; <2> The method described below. <10> A method for treating an individual whose sleep-wake cycle is disrupted by an advance of 8 hours or less at the individual's usual bedtime, comprising administering 20 mg of tasimelteon per day in an immediate-release dosage form to the individual within 1 hour before bedtime for at least three consecutive days, wherein the first dose is administered before the first bedtime after the advance that disrupts the sleep-wake cycle. <11> the individual experiences disruptive sleep-wake cycles as a result of eastbound jet travel, <10> The method described below. <12> the individual experiences a significant improvement in total sleep time in the first two-thirds of the night on both subjective and objective sleep measures on the night after administration of the third dose of tasimelteon; <11> The method described below. <13> the individual is known to be in need of treatment to reduce one or more adverse effects of a subsequent disruption of the individual's sleep-wake cycle due to a history of disrupting the individual's sleep-wake cycle; <10> The method described below. <14> the individual is known to experience adverse effects of disruption of the individual's normal sleep-wake cycle due to eastbound jet travel; <13> The method described below. <15> Advances that disrupt the sleep-wake cycle occur after arrival on an eastbound jet flight to a destination that is up to eight hours ahead of the time at the flight's departure point. <10> The method described below. <16> the individual is known to be in need of treatment to reduce one or more adverse effects of a subsequent disruption of the individual's sleep-wake cycle due to a history of disrupting the individual's sleep-wake cycle; <15> The method described below. <17> The individual is administered 20 mg of tasimelteon per day in an immediate-release form within one hour before bedtime for three consecutive days, the first dose being administered prior to the first bedtime after the sleep-wake cycle disrupting advance. <16> The method described below. <18> The individual is administered 20 mg of tasimelteon per day in an immediate-release form within one hour before bedtime for three consecutive days, the first dose being administered prior to the first bedtime after the sleep-wake cycle disrupting advance. <15> The method described below. <19> the individual experiences an increase in total REM sleep time, a decrease in the time to reach 30 cumulative minutes of REM sleep, or both. <11> The method described below. <20> 1. A method for treating jet lag in an individual who has experienced eastward travel from a departure location through six to eight time zones to a destination location during overnight airplane travel, comprising orally administering to the individual an immediate-release form of 20 mg tasimelteon after arrival at the destination location at or before the individual's bedtime at the destination. <21> before the individual's bedtime at the destination location means between 30 minutes and 2 hours before the individual's bedtime corresponding to the individual's normal bedtime at the individual's departure location; <20> The method described below. <22> before the individual's bedtime at the destination location means within 1.5 hours of such bedtime; <20> The method described below. <23> before the individual's bedtime at the destination location means within one hour of such bedtime; <20> The method described below. <24> before the individual's bedtime at the destination location means within 0.5 hours of such bedtime; <20> The method described below. <25> The individual is pre-selected based on having previously experienced jet lag as a result of a similar travel experience. <20> The method described below. <26> Tasimelteon is administered to the individual once daily for at least three days. <20> The method described below. <27> the individual experiences an eastward journey through eight time zones; <20> The method described below. <28> A method for treating an individual whose sleep-wake cycle is disrupted by an advance of 8 hours or less at the individual's usual bedtime, comprising administering 20 mg of tasimelteon per day in an immediate-release dosage form to the individual within 1 hour before bedtime for at least three consecutive days, the first dose being administered before the first bedtime after the advance that disrupts the sleep-wake cycle. <29> A method for reducing the adverse effects of an 8-hour advance in an individual's usual bedtime, comprising administering 20 mg of tasimelteon in an immediate-release dosage form to the individual before the individual's advanced bedtime for at least three consecutive days, the first dose being administered before the first advanced bedtime. <30> (a) a plurality of individual tasimelteon unit doses, each containing 20 mg of immediate-release tasimelteon, sufficient to provide a course of treatment for an individual being treated for jet lag disorder; and (b) a pharmaceutically acceptable container for said unit dose. 1. A packaged dispensing unit comprising: <31> the number of unit doses in the dosage unit is 3, 4, or 5, and the container for the dosage unit is a blister pack containing one 20 mg tasimelteon tablet per blister; <30> The dispensing unit according to claim 1.

Claims

1. 1. A pharmaceutical composition comprising tasimelteon for use in reducing one or more adverse effects of an individual's usual advancement of bedtime, comprising: The pharmaceutical composition, wherein the use comprises administering 20 mg of tasimelteon per day to the individual before bedtime for at least three consecutive days, the first dose being administered before the first bedtime after the advance.

2. 10. The pharmaceutical composition of claim 1, wherein the advance in the individual's default bedtime is an 8-hour advance caused by eastward jet travel.

3. 3. The pharmaceutical composition of claim 2, comprising 20 mg of tasimelteon in immediate release dosage form.

4. 4. The pharmaceutical composition of claim 3, wherein the reduction in adverse effects is an improvement in at least one sleep parameter selected from the group consisting of total sleep time, latency to fall asleep, and wake-after-sleep time.

5. 5. The pharmaceutical composition of claim 4, wherein the improved sleep parameter is total sleep time.

6. 6. The pharmaceutical composition of claim 5, wherein on the third night after administration of tasimelteon, total sleep time in the first two-thirds of the night is improved.

7. 4. The pharmaceutical composition of claim 3, wherein the reduction in adverse effects is an improvement in next-day alertness.

8. 8. The pharmaceutical composition of claim 7, wherein the improvement in next-day alertness comprises an improvement in the Karolinska Sleepiness Scale, an improvement in the Visual Analogue Scale, or both.

9. 1. A method for treating jet lag in an individual who has experienced eastward travel from a departure location through six to eight time zones to a destination location during overnight airplane travel, the method comprising administering 20 mg tasimelteon in immediate release form to the individual at or before bedtime at the destination location after arrival at the destination for at least three consecutive days.

10. 10. The therapeutic agent of claim 9, wherein before the individual's bedtime at the destination location means between 30 minutes and 2 hours before the individual's bedtime corresponding to the individual's normal bedtime at the individual's departure location.

11. 10. The method of claim 9, wherein before the individual's bedtime at the destination location means within 1.5 hours of such bedtime.

12. The method of claim 9 , wherein before the individual's bedtime at the destination location means within one hour of such bedtime.

13. The method of claim 9, wherein before the individual's bedtime at the destination location means within 0.5 hours of such bedtime.

14. 10. The therapeutic agent of claim 9, wherein the individual is preselected based on having previously experienced jet lag as a result of a similar travel experience.

15. 10. The method of claim 9, wherein the individual experiences an eastward journey through eight time zones.

16. (a) a plurality of individual tasimelteon formulations, each containing 20 mg of immediate-release tasimelteon, sufficient to provide a course of treatment for an individual being treated for jet lag disorder; and (b) a pharmaceutically acceptable container for said individual tasimelteon formulation. A pre-packaged dispensing unit for treating jet lag disorder, including:

17. 17. The dispensing unit of claim 16, wherein the number of individual formulations in the dispensing unit is 3, 4, or 5, and the container for the dispensing unit is a blister pack containing one 20 mg tasimelteon tablet per blister.

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