0830 Effects of Elinzanetant on Wakefulness After Sleep Onset in Postmenopausal Women: Post Hoc Analysis of NIRVANA Study

Abstract Introduction Nighttime wakefulness is common among postmenopausal women with vasomotor symptoms (VMS). Elinzanetant has previously shown improvements in patient-reported sleep outcomes in this population. The Phase II NIRVANA trial was the first to evaluate elinzanetant’s effect on wakefulness after sleep onset (WASO) using both objective (polysomnography [PSG], Sleepiz One+) and subjective (Sleep Diary) measures. This post hoc analysis compared changes in WASO with elinzanetant across all three modalities. Methods NIRVANA randomized 110 postmenopausal women with PSG-confirmed WASO ≥30 minutes and ≥20 moderate-to-severe VMS/week to elinzanetant 120 mg (n=55) or placebo (n=55) once daily for 12 weeks. Sleep disturbances were assessed using in-lab PSG and patient-reported Sleep Diary for all participants, and with the contactless home-monitoring device Sleepiz One+ in a subset (elinzanetant: n=33, placebo: n=33). PSG assessments occurred at baseline, week 4, and week 12 (two consecutive nights/timepoint). Sleepiz One+ and diary data were collected nightly. WASO values were analyzed on the original scale for consistency in presentation across measures. A post hoc random coefficient model estimated overall treatment effects over 12 weeks for each modality. Results Elinzanetant demonstrated numerical reductions in WASO versus placebo across all assessment modalities. PSG: Baseline mean (standard deviation [SD]) WASO was 74.7 (34.8) minutes for elinzanetant and 82.8 (34.4) minutes for placebo. Overall treatment effect favored elinzanetant (least squares [LS] mean difference: -10.1 minutes; unadjusted 95% confidence interval [CI]: -18.5, -1.6). Sleepiz One+: Baseline mean (SD) WASO was 77.7 (52.6) minutes for elinzanetant and 61.7 (27.6) minutes for placebo. Overall treatment effect favored elinzanetant (LS mean difference: -17.7 minutes; unadjusted 95% CI: -27.1, -8.2). Sleep Diary: Baseline mean (SD) WASO was 42.4 (25.7) minutes for elinzanetant and 45.5 (25.6) minutes for placebo. Overall treatment effect favored elinzanetant (LS mean difference: -8.1 minutes; unadjusted 95% CI: -14.2, -1.9). Conclusion Greater reductions in WASO were observed with elinzanetant versus placebo across all modalities, consistent with previously reported improvements in sleep disturbances from the OASIS trials. While exploratory in nature, these findings support elinzanetant’s potential use in improving sleep disturbances in menopausal women with VMS. Support (if any) Sponsored by Bayer. Medical writing assistance (Highfield, Oxford, UK) funded by Bayer.