Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder

The purpose of this study is to evaluate the maintenance effect and safety of 20 mg tasimelteon versus placebo in subjects suffering from Non-24-Hour Sleep-Wake Disorder.

Non-24-Hour Sleep-Wake Disorder (N24HSWD) occurs when individuals are unable to synchronize their endogenous circadian pacemaker to the 24-hour light-dark cycle, and the timing of their circadian rhythm instead reflects the intrinsic period of their endogenous circadian pacemaker. As a result, the circadian rhythm of sleep-wake propensity in these individuals moves gradually later and later each day if there circadian period is \> 24 hours and earlier and earlier is \< 24 hours. These individuals will be able to sleep well at night when their sleep-wake propensity rhythm is approximately aligned with the 24-hour light-dark and social cycle. However, after a short time, the endogenous sleep-wake propensity rhythm and the 24-hour light-dark cycle will move out of synchrony with each other, and they may have difficulty falling asleep until well into the night. In addition to problems sleeping at the desired time, the subjects experience daytime sleepiness and daytime napping. As time progresses, the endogenous circadian rhythm of sleep-wake propensity in these individuals moves further and further away from the 24-hour light-dark cycle and gradually, these individuals are unable to sleep at night and as a result experience extreme sleepiness during the daytime hours and more frequent naps with a longer duration. Eventually, the sleep-wake time moves back into alignment with the social time for sleep and the individuals sleep well at night and have decreased daytime napping. The alignment between their endogenous circadian rhythms and the 24-hour day is temporary as they are continually drifting later and later each day. This will be a multicenter, randomized withdrawal, double-masked, placebo-controlled, parallel study. The study has three phases: the tasimelteon run-in phase, the tau estimation phase, and the randomized withdrawal phase. Subjects who have participated in study VP-VEC-162-3201 that meet the entry criteria for this study will be eligible for the run-in phase The run-in phase comprises a screening visit where subject's initial eligibility will be evaluated. Subjects that meet the inclusion/exclusion criteria at screening will enter the run-in phase and will be dosed with 20 mg of tasimelteon daily for 6 weeks. The tau estimation phase (48 hour urine collection samples to evaluate response to tasimelteon) will follow the run-in phase and will last approximately 6 weeks long. The randomized withdrawal phase comprises approximately eight weeks of treatment with either placebo or tasimelteon 20 mg taken approximately 1 hour prior to their target bedtime in a double-masked fashion.