Phase 2 Double-Blind Randomized Study on the Efficacy and Safety of Elinzanetant Versus Placebo for Menopausal Sleep Disturbances

The primary objective of this study is to explore the **efficacy** of elinzanetant on sleep disturbances associated with menopause, as determined by polysomnography (PSG). This is clinically relevant as sleep disturbances are a common and disruptive symptom of menopause, impacting quality of life and overall health. Understanding the efficacy of elinzanetant could provide a targeted therapeutic option for managing these symptoms.

Secondary objectives include:

• To explore the efficacy of elinzanetant on sleep disturbance associated with menopause as determined by patient-reported outcomes.
• To evaluate the safety of elinzanetant for the treatment of sleep disturbances associated with menopause.

The clinical trial investigating the efficacy of **elinzanetant** on sleep disturbances associated with menopause involves a total of 51 participants. The study population consists exclusively of **females** aged between 40 to 65 years, who are in the post-menopausal period. Participants were selected based on specific criteria, including serum follicle-stimulating hormone (FSH) levels greater than 40 mIU/mL and serum estradiol concentration below 30 pg/mL. Additionally, participants must have undergone a hysterectomy at least six weeks prior to screening. The trial focuses on individuals with self-reported sleep disturbances related to menopause, characterized by waking up at night and/or poor quality of sleep, with a wake after sleep onset (WASO) of 30 minutes or more. The trial does not include male subjects or vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection process.

The clinical trial is designed as a **randomized**, parallel-group, Phase 2, **double-blind** pilot study to evaluate the efficacy and safety of **elinzanetant** compared to a placebo in treating sleep disturbances associated with menopause. The trial will involve female participants aged 40 to 65 years who are in the post-menopausal period, as defined by specific hormonal criteria. The study will assess changes in wake after sleep onset (WASO) and other sleep-related parameters over a 12-week period, with primary and secondary endpoints measured at Weeks 4 and 12 using polysomnography (PSG) and other validated scales.

Participants will be involved in the study for approximately 12 weeks, with the trial expected to conclude by January 2025. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as hormonal levels and self-reported sleep disturbances. Following randomization, participants will attend regular follow-up visits to monitor treatment effects and safety, with assessments conducted at Weeks 4 and 12. The end-of-study visit will occur at the conclusion of the 12-week treatment period, where final evaluations will be performed.

Participant involvement may be terminated early if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial will utilize a placebo control to ensure the reliability of the results, with both the participants and investigators blinded to the treatment assignments. The study aims to provide valuable insights into the potential benefits of elinzanetant for improving sleep quality in post-menopausal women.

The clinical trial involves the administration of **BAY 3427080**, an experimental medication, to evaluate its efficacy and safety in treating sleep disturbances associated with menopause. **BAY 3427080** is formulated as a soft capsule and contains the active substance **elinzanetant**. The medication is administered orally with a maximum daily dose of 120 mg, and the total dose over the treatment period should not exceed 10,080 mg. The treatment duration is set for a maximum of 12 weeks. The pharmaceutical product is manufactured by Bayer AG and is of chemical origin. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** group to serve as a comparator for the experimental treatment. The placebo is designed to mimic the appearance of the **BAY 3427080** soft capsule but does not contain the active substance **elinzanetant**. The placebo is administered orally with the same frequency and schedule as the experimental medication to ensure blinding and maintain the integrity of the study design. The use of a placebo allows for the assessment of the true efficacy of **BAY 3427080** by comparing outcomes between the treatment and placebo groups.

The efficacy of elinzanetant in treating sleep disturbances associated with menopause will be assessed through a randomized, parallel-group, double-blind, Phase 2 clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in **WASO** (Wake After Sleep Onset) at Week 4, as measured by polysomnography (PSG). Secondary endpoints include changes from baseline in WASO at Week 12, changes in Sleep Efficiency (SE) at Weeks 4 and 12, and changes in the PROMIS Sleep Disturbance Short Form 8b total score and Insomnia Severity Index (ISI) total score at Weeks 4 and 12. Additionally, the trial will monitor treatment-emergent adverse events (TEAEs) and abnormal laboratory parameters as part of the efficacy assessment. The efficacy parameters will be collected and analyzed at specified timepoints, including Week 4 and Week 12, using validated scales and PSG, ensuring a comprehensive evaluation of the treatment's impact on sleep disturbances in post-menopausal women.