Zuranolone for sleeplessness promising in early study

The orally bioavailable, investigational neuroactive steroid zuranolone appears to be beneficial in the treatment of insomnia, producing improvements in sleep measures, including sleep efficiency, duration of awakenings, and total sleep time in adults, according to the results of a phase I study.

The study included 45 healthy and ambulatory participants, with body weight ≥50 kg and a body mass index (BMI) between 18 and 32 kg/m², had a Pittsburgh Sleep Quality Index score of ≤5, and an Epworth Sleepiness Scale score of ≤10, indicating normal sleep quality (SQ) and lack of excessive daytime sleepiness. They were randomized to receive zuranolone 30 mg (n=44), zuranolone 45 mg (n=42), or placebo (n=41).

All participants completed a sleep diary for a minimum of 6 consecutive days between screening and qualification polysomnography (PSG), confirming habitual bed and rise times within 1-h time frames and a routine time in the bed of 7–9 hours.

Thirty-six participants (80 percent) completed the study. Compared with those on placebo, participants who received zuranolone showed significant improvements in median sleep efficiency (30 mg, 84.6 percent; 45 mg, 87.6 percent; placebo, 72.9 percent; 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 with the investigational drug relative to placebo.

Zuranolone was generally well tolerated. Headache and fatigue were the most common adverse events (≥2 participants, any period).