Elinzanetant in postmenopausal women with sleep disturbance: results from the randomized, phase II NIRVANA study

Menopausal sleep disturbances can negatively impact quality of life. Elinzanetant, a dual neurokinin (NK)-1/NK-3 receptor antagonist, reduced self-reported sleep disturbance in postmenopausal women with moderate-to-severe vasomotor symptoms (VMS) in Phase III OASIS trials. NIRVANA explored elinzanetant's effect on multimodal measures of objective and subjective sleep disturbance in postmenopausal women.

Postmenopausal women (N = 110; 40-65 years) with moderate-to-severe VMS (≥20/week) and sleep disturbance (polysomnography [PSG] wakefulness after sleep onset [WASO] ≥30 min) were randomized 1:1 to receive elinzanetant 120 mg or placebo for 12 weeks. Sleep disturbance was assessed using PSG; daily Sleep Diary; and nightly contactless home-monitoring (Sleepiz One+ subgroup). The effect of elinzanetant versus placebo was analyzed using mixed-model repeated measures.

Elinzanetant was estimated to reduce PSG WASO at Week 4 versus placebo (least square [LS]-mean difference = -22.50 minutes, 90% CI: -35.47, -9.52). Minimal group differences between treatment arms were estimated at Week 12 for PSG WASO (LS-mean difference = -0.94 minutes, 90% CI: -13.96, 12.09). When including all available PSG data across the 12-week period, post hoc random coefficient modeling indicated treatment effects favoring elinzanetant for WASO, total sleep time, sleep efficiency, latency to persistent sleep, number of awakenings, arousal index, and % Stage N2 sleep. Treatment effects on WASO and awakenings favoring elinzanetant were observed with Sleepiz One+ and Sleep Diary across 12 weeks.

In this sleep-focused study, elinzanetant reduced WASO at Week 4 and led to estimated improvements in sleep continuity over 12 weeks, supported by multimodal subjective and objective sleep outcomes.

A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause (NIRVANA), https://clinicaltrials.gov/study/NCT06112756, NCT06112756, date of registration 2023-11-01.