Evaluating the Effects of Tasimelteon vs. Placebo on Jet Lag Type Insomnia

• Tasimelteon (Drug): Oral capsule
• Placebo (Drug): Oral capsule

Primary outcomes

• Total Sleep Time in the First Two Thirds of the Night [1 Day]: Total sleep time during the first 2/3 of the night following an 8-hour phase advance bedtime, as measured by PSG. This is representative of trans meridian travel across 8 time zones.

Secondary outcomes

• Total Sleep Time [1 Day]: Total Sleep Time as measured by PSG.
• Latency to Persistent Sleep [1 Day]: Length of time elapsed between lights out and onset of persistent sleep as measure by PSG.
• Wake After Sleep Onset [1 Day]: The amount of wake time during the sleep period after sleep onset (as measured by polysomnography).
• Next Day Alertness as Measured by the Karolinska Sleepiness Scale (Night 1 Average Score) [1 Day]: A 9-point scale that measures subjective levels of fatigue by asking how sleepy subjects feel at that moment: 1 = extremely awake to 9 =extremely sleepy/fighting to stay awake.
• Next Day Alertness as Measured by the Visual Analogue Scale (Night 1 Average Score) [1 Day]: The VAS was a self-rated scale to assess sleepiness. Participants marked along a 100 mm line to represent their current state of sleepiness, 0 being very sleepy and 100 being very alert. The VAS was administered four times following the dose administration after awakening.

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

* Ability and acceptance to provide written consent, fluent in English;
* Healthy subjects with no medical, psychiatric or current sleep disorders;
* Men or women between 18-75 years;
* Body Mass Index of ≥ 18 and ≤ 30 kg/m2.

Exclusion Criteria:

* Major surgery, trauma, illness or immobile for 3 or more days within the past month;
* Pregnancy or recent pregnancy (within 6 weeks);
* A positive test for drugs of abuse at the screening or evaluation visit.

Participant flow

Outcome results

• Total Sleep Time in the First Two Thirds of the Night (Primary), Least squares mean, Minutes: Placebo 156.1 +/- 80.67; Tasimelteon 216.4 +/- 69.69 (p <.0001)
• Total Sleep Time (Secondary), Least squares mean, Minutes: Placebo 230.3 +/- 97.39; Tasimelteon 315.8 +/- 95.51 (p <.0001)
• Latency to Persistent Sleep (Secondary), Least squares mean, Minutes: Placebo 36.8 +/- 63.56; Tasimelteon 21.8 +/- 33.69 (p <.0001)
• Wake After Sleep Onset (Secondary), Least squares mean, Minutes: Placebo 219.1 +/- 96.90; Tasimelteon 144.6 +/- 86.73 (p <.0001)
• Next Day Alertness as Measured by the Karolinska Sleepiness Scale (Night 1 Average Score) (Secondary), Least squares mean, Night 1 average score: Placebo 4.5 +/- 1.86; Tasimelteon 4.0 +/- 1.77 (p 0.0083)
• Next Day Alertness as Measured by the Visual Analogue Scale (Night 1 Average Score) (Secondary), Least squares mean, Night 1 Average Score in millimeters: Placebo 54.2 +/- 23.46; Tasimelteon 60.8 +/- 22.24 (p 0.0099)

Adverse events

Time frame: AE Data collected over the 1 Day/ 1 Night study plus a 30 day follow up period

Serious adverse events by term

Other adverse events by term

• Results publication: Polymeropoulos CM, Mohrman MA, Keefe MS, Brzezynski JL, Wang J, Prokosch LS, Polymeropoulos VM, Xiao C, Birznieks G, Polymeropoulos MH. Efficacy of Tasimelteon (HETLIOZ(R)) in the Treatment of Jet Lag Disorder Evaluated in an 8-h Phase Advance Model; a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Front Neurol. 2020 Jul 9;11:611. doi: 10.3389/fneur.2020.00611. eCollection 2020. PMID 32754110

• Study Protocol and Statistical Analysis Plan (PDF, 2018-02-23)