A phase 1 double-blind, placebo-controlled study of zuranolone (SAGE-217) in a phase advance model of insomnia in healthy adults

Objective To evaluate single zuranolone (SAGE-217) 30 or 45 mg doses in a 5-h phase advance insomnia model. Methods In this double-blind, three-way crossover study, healthy adults received placebo (n = 41), zuranolone 30 mg (n = 44), and zuranolone 45 mg (n = 42) across three treatment periods. Sleep was assessed by polysomnography and a postsleep questionnaire. Next-day residual effects and safety/tolerability were evaluated. Results Compared with placebo, zuranolone resulted in significant improvements in median sleep efficiency (30 mg, 84.6%; 45 mg, 87.6%; placebo, 72.9%; p < 0.001 for both doses), wake after sleep onset (WASO; 30 mg, 55.0 min; 45 mg, 42.5 min; placebo, 113.0 min; p < 0.001 for both doses), duration of awakenings (30 mg, 4.2 min, p < 0.001; 45 mg, 3.7 min, p = 0.001; placebo, 7.4 min), and total sleep time (TST; 30 mg, 406.3 min; 45 mg, 420.3 min; placebo, 350.0 min; p < 0.001 for both doses). Subjective endpoints (WASO, TST, sleep latency, sleep quality) also improved relative to placebo. Zuranolone was generally well tolerated, and the most common adverse events (>= 2 participants, any period) were headache and fatigue. Conclusion Zuranolone improved sleep measures versus placebo in a phase advance model of insomnia in healthy adults, supporting future studies in patients with insomnia disorder.