TABLE 6 

Summary of studies assessing the effects of tasimelteon (TMT) on sleep

StudyAgeDiagnosisDesign + Number of ParticipantsResultsAdverse EventsConclusion
Johnsa and Neville (2014)HeterogeneousHeterogeneousReview of four RCTs.In one phase II trial, significant shifts in circadian rhythm were observed only for TMT 100 mg/day. In a phase III trial, LPS was significantly improved in the TMT group relative to placebo. The SET and RESET trials both found TMT to significantly improve entrainment in non-24-hour sleep-wake disorder patients.Frequency and severity of AEs were similar across treatment groups. Most common AEs were somnolence and headache.TMT is effective at reducing symptoms of non-24-hour sleep-wake disorder.
Lockley et al. (2015)18–75Total blindness with non-24-hour sleep-wake disorderTwo RCTs, SET (26 wk, N = 84) and RESET (19 wk, N = 20). TMT 20 mg/day vs. placebo.TMT significantly improved entrainment, although the effect did not last after discontinuation.No significant difference in the discontinuation rate due to AEs between the TMT (6%) and placebo (4%) groups. Headache and increased alanine aminotransferase occurred in more patients receiving TMT than placebo.TMT is effective at reducing symptoms of non-24-hour sleep-wake disorder.
NCT#0054834018–65Primary insomnia5-wk RCT. TMT 20 vs. 50 mg/day vs. placebo. N = 321.Statistics were not conducted. Mean change in LPS [S.E.] was 45.0 [2.965] for TMT 20 mg/day, 46.4 [2.954] for TMT 50 mg/day, and 28.3 [3.020] for placebo. Mean change in TST was 51.4 [4.794], 52.0 [4.775], and 39.9 [4.882] for the same respective groups.Most common AEs were nasopharyngitis and headache.Statistics were not conducted.
Rajaratnam et al. (2009)Phase II RCT: 18–50. Phase III RCT: 21–50.Phase II RCT: healthy volunteers. Phase III RCT: healthy volunteers with induced transient insomniaTwo RCTs. Phase II RCT: TMT 10 vs. 20 vs. 50 vs. 100 mg/day vs. placebo. N = 39. Phase III RCT: TMT 20 vs. 50 vs. 100 mg/day vs. placebo. N = 411.In the phase II RCT, TMT reduced SOL and increased SE compared with placebo. In the phase III study, TMT improved SOL, SE, and WASO. LPS was significantly reduced relative to placebo: in phase II study, TMT 10 mg/day, P = 0.003; 50 mg/day, P = 0.019; 100 mg/day, P = 0.021. In the phase III study, all doses of TMT, P < 0.001 for reducing LPS.Rates of AEs were similar between TMT and placebo.TMT is effective at reducing symptoms of insomnia in a model of circadian rhythm disorders.