0831 Elinzanetant’s Effects in Reducing Polysomnographic Wakefulness After Sleep Onset in Postmenopausal Women: Phase II NIRVANA Exploratory Study Results

Abstract Introduction Sleep disturbances are common among menopausal women with vasomotor symptoms (VMS). Elinzanetant has previously demonstrated patient-reported outcome (PRO) improvements in sleep disturbances in the OASIS studies. The Phase II NIRVANA trial further evaluated elinzanetant’s effect on sleep parameters using objectively-measured polysomnography (PSG), in addition to PROs. This abstract reports effect on PSG-measured wakefulness after sleep onset (WASO) at weeks 4 and 12. Methods NIRVANA included 110 menopausal women with PSG-measured WASO ≥30 minutes and ≥20 moderate-to-severe VMS/week, randomized to elinzanetant 120mg (n=55) or placebo (n=55) once daily for 12 weeks. In-lab PSG assessments occurred at baseline, week 4, and week 12 (two consecutive nights/time point). Primary and secondary endpoints were changes from baseline in WASO at weeks 4 and 12, respectively, analyzed using mixed model with repeated measures. A prespecified analysis with log transformation was applied; least squares geometric mean ratios (LSGMR) are reported. Post hoc random coefficient model was applied to all individual night data to assess overall treatment effect and account for night-to-night variability. Results Baseline median WASO was 72.0 minutes (quartile [Q]1, Q3: 48.0, 90.3) for elinzanetant and 76.8 minutes (Q1, Q3: 54.0, 102.5) for placebo. At week 4, LSGMR to baseline was 0.68 (unadjusted 90% confidence interval [CI]: 0.59, 0.77) for elinzanetant and 0.94 (0.82, 1.08) for placebo, representing a 28% (unadjusted 90% CI: 13%, 41%) greater reduction with elinzanetant. At week 12, LSGMRs were 0.67 (0.57, 0.79) for elinzanetant and 0.76 (0.65, 0.90) for placebo, representing a 12% (-11%, 30%) greater reduction with elinzanetant. Night-to-night variability was notable, with WASO differing by >60 minutes in 15% of consecutive nights. The random coefficient model showed an 18% (unadjusted 95% CI: 5%, 30%) greater WASO reduction with elinzanetant vs. placebo, equating to an absolute reduction of ~13 minutes across the 12-week treatment period (assuming a baseline of 75 minutes). Conclusion Elinzanetant had a numerically greater reduction in WASO vs. placebo, an effect more pronounced at week 4. The modest but relevant improvement supports the effect of elinzanetant on menopause-related sleep disturbances, consistent with PROs from the OASIS trials. Support (if any) Sponsored by Bayer. Medical writing assistance (Highfield, Oxford, UK) funded by Bayer.