Session: SUN 130-162-Neuroendocrinology
Poster Board SUN-137
Methods: The RESET (Randomized-withdrawal study of the Efficacy and Safety of Tasimelteon to treat Non-24) is a multicenter, double-masked, placebo-controlled investigation of the maintenance effect of tasimelteon to treat Non-24 in totally blind patients. Patients were treated with 20mg open-label tasimelteon 1 hour before bedtime for 3 months. Patients who responded, defined as entrainment of their circadian clock to a 24 hour day (confirmed with urinary 6-sulfatoxymelatonin, aMT6s), were randomized to receive tasimelteon 20mg or placebo for 2 months. aMT6s and cortisol circadian periods were reassessed after randomization. Subjective nighttime sleep and daytime naps were reported daily throughout the study.
Results: 20 entrained totally blind patients (8F, age 28-70 yrs) were randomized to continue treatment or receive placebo. Tasimelteon-treated patients maintained entrainment of their circadian rhythms compared to placebo (aMT6s: 90% tasimelteon vs. 20% placebo p=0.0026; cortisol: 80% tasimelteon vs. 20% placebo p=0.0118). Total nighttime sleep in the worst quartile of nights was 67.2 minutes longer and total daytime sleep duration was 59.4 minutes shorter in tasimelteon-treated patients (p< 0.05). The midpoint of sleep timing from both nighttime and daytime sleep increased 36 minutes in tasimelteon treated patients (p=0.0108). Tasimelteon was safe and well-tolerated.
Conclusion: Tasimelteon entrained circadian rhythms as measured by melatonin and cortisol in totally blind patients with Non-24. Discontinuation of tasimelteon resulted in loss of entrainment which was correlated with an approximate 60 minute decrease in nighttime sleep and an equivalent increase in daytime napping. The RESET study demonstrates the necessity for chronic treatment with tasimelteon in Non-24.
Disclosure: SWL: Investigator, Vanda Pharmaceuticals Inc. . MAD: Employee, Vanda Pharmaceuticals Inc. . CX: Employee, Vanda Pharmaceuticals Inc. . LL: Employee, Vanda Pharmaceuticals Inc. . MHP: , Vanda Pharmaceuticals Inc. .
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