Tasimelteon, a novel dual-melatonin receptor agonist, effectively entrains circadian rhythm in totally blind patients with non-24-hour sleep-wake disorder, according to research published in The Lancet.
The effects, however, are only sustained with continued treatment with tasimelteon, Steven W. Lockley, PhD, of Harvard Medical School and Brigham and Women’s Hospital, and colleagues found.
The researchers conducted 2 placebo-controlled, randomized, double-blind, phase 3 clinical trials to study the effects of tasimelteon implementation and withdrawal in totally blind patients with non-24 sleep disorder. The SET trial included 84 blind patients randomized to receive 20 mg of tasimelteon (n=42) or placebo (n=42) every 24 hours at a fixed time before target bedtime for 26 weeks. In the RESET trial, which included 48 patients, tasimelteon was withdrawn in a randomized manner in patients who responded to tasimelteon after a run-in period.
In SET, circadian entrainment occurred in 8 out of 40 patients (20%) in the tasimelteon group compared to 1 out of 38 patients (3%) in the placebo group at 1 month (difference 17%, 95% CI 3.2–31.6; P=0.0171). Twenty-four percent of patients in the tasimelteon group showed a clinical response compared to none of the participants in the placebo group (difference 24%, 95% CI 8.4–39.0; P=0.0028).
Forty-eight patients were included in the open-label tasimelteon run-in phase in RESET, 24 (50%) of whom entrained. Of the 20 (34%) patients who were enrolled in the trial’s randomization phase, 2 of 10 (20%) who were withdrawn to placebo remained entrained compared to 9 of 10 (90%) who continued to receive tasimelteon (difference 70%, 95% CI 26.4–100.0; P=0.0026).
The researchers reported no deaths in either study. The most common side effects in patients treated with tasimelteon included headache, elevated liver enzymes, nightmares or abnormal dreams, upper respiratory tract infection, and urinary tract infection.