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

Abstract Study Objectives 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. Materials and methods 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. Results 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. Conclusion 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. Clinical Trial 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.