SEATTLE, WA—E2006, a novel dual orexin receptor antagonist (DORA), has shown efficacy for both subject-reported sleep onset and maintenance on sleep diary measures, according to Phase 2 study results reported at SLEEP 2015.
“These data highlight the potential of E2006 to treat insomnia disorder,” stated Margaret Moline, PhD, of Eisai Inc, Woodcliff Lake, NJ.
The multicenter, randomized, double-blind, placebo-controlled, parallel group design study enrolled subjects with insomnia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) classification.
Using a Bayesian adaptive design, six strengths of E2006 (1mg, 2.5mg, 5mg, 10mg, 15mg, 25mg) or placebo administered for 15 nights, 30 minutes before bedtime were tested. Each morning, the subjects completed a sleep diary. Safety was monitored via treatment-emergent adverse events (AEs), ECGs, vital signs, chemistries and, for those treated in the clinic, morning assessments of residual sleepiness.
Sleep efficiency, subjective Sleep Onset Latency, and subjective Wake After Sleep Onset from sleep diaries were averaged for baseline and during treatment days 1–7 and 8–15. A total of 616 subjects were screened and 291 were randomly assigned to doses of E2006 (n=235) or placebo (n=56). More than half of the subjects were female (62%) and mean age was 48±14 years. Mean baseline Insomnia Severity Index (ISI) score was 20±3 (moderate-severe).
Baseline characteristics were similar between treatment groups. Overall mean baseline values were 64±12% for sleep efficiency, 61±32 minutes for subjective Sleep Onset Latency, and 118±56 minutes for subjective Wake After Sleep Onset. A total of 94.5% of subjects in the E2006 arm and 91.1% of those in the placebo arm completed the study.
During Days 1–7, the least squares (LS) mean difference for E2006 vs. placebo for change from baseline in sleep efficiency was significant for 5–25mg, increasing 6% to 9.4%, with overlapping confidence intervals.
With the exception of the 1mg dose, subjective Sleep Onset Latency decreased significantly; median change from baseline was from -23 minutes (2.5mg) to -26 minutes (25mg) for the E2006 arm compared with placebo, which was -10 minutes. Subjective Wake After Sleep Onset decreased in all treatment groups and was significant at the 10mg dose; LS mean difference was -29 minutes.
The benefits observed for Days 1–7 were maintained for Days 8–15, Dr. Moline reported. Treatment-emergent AEs were more common with E2006; somnolence was dose-related. There were two serious AEs, one in the placebo arm and one at the E2006 25mg dose; the latter of which resulted in study discontinuation. All treatment-emergent AEs, which with exception of the one serious AE, were mild or moderate.