A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause

Study Overview
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Brief Summary
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Researchers are looking for a better way to treat women who have sleep disturbances associated with menopause. Menopause is part of a natural aging process and happens when women's menstrual cycles, also called periods, stop. Sleep disturbances, for example, frequent waking up at night, are a common and bothersome symptom associated with menopause that affects women's quality of life. The study treatment Elinzanetant (also called BAY 3427080) is under development to treat symptoms like hot flashes which are caused by hormonal changes associated with menopause. It may block the activity of a protein that has been found to contribute to sleep disturbances. The main purpose of this study is to learn how does elinzanetant affect sleep disturbances associated with menopause as measured on a sleep test called polysomnography (PSG) as compared with placebo. For this, the researchers will analyze change in the total number of minutes a participant wakes up at night after going to sleep after 4 weeks of treatment compared to before treatment change in the total number of minutes a participant wakes up at night after going to sleep after 12 weeks of treatment compared to before treatment change in the participant's total time asleep while in bed after 4 and 12 weeks of treatment compared to before treatment. The study participants will be randomly (by chance) assigned to one of two treatment groups. Dependent on the group, they will take elinzanetant or placebo for 12 weeks. Each participant will be in the study for approximately 22 weeks (plus potential washout period), including a screening phase of up to 6 weeks, 12 weeks of treatment, and a follow up phase of 4 weeks after the end of treatment. 5 visits to the study site are planned. During the study, the doctors and their study team will: take blood and urine samples do physical examinations check vital signs do sleep tests use an electronic hand-held device to record sleep quality and hot flashes at home An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.

Official Title
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A Randomized, Parallel-group Treatment, Phase 2, Double-blind Pilot Study to Investigate the Efficacy and Safety of Elinzanetant Compared With Placebo for Treatment of Sleep Disturbances Associated With Menopause.

Conditions
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Sleep Disturbances Associated With Menopause

Intervention / Treatment
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* Drug: Elinzanetant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 40 to 65 years, inclusive, at signing of informed consent. Being in the post-menopausal period, defined as: serum FSH levels >40 mIU/mL and a serum estradiol concentration of <30 pg/mL at screening, AND Hysterectomy performed at least 6 weeks prior to screening. The participant's self-reported sleep history includes ongoing sleep disturbances associated with menopause characterized by waking up at night and/or poor quality of sleep. WASO of 30 minutes or more (mean of 2 screening PSGs with neither of the 2 nights <20 min). Exclusion Criteria: Medical history, or baseline PSG assessment, includes a diagnosis of a sleep disorder other than sleep disturbances associated with the menopause (e.g., sleep apnea, restless leg syndrome, circadian rhythm sleep disorder). Current or history (except complete remission for 5 years or more) of any malignancy (except basal and squamous cell skin tumors). Renal impairment greater than moderate (i.e. estimated glomerular filtration rate <30 mL/min/1.73 m^2) at screening

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elinzanetant arm<br>Participants will take Elinzanetant | Drug: Elinzanetant<br>* Oral<br>|
| Placebo Comparator: Placebo arm<br>Participants will take elinzanetant matching placebo | Other: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in WASO as measured by PSG | WASO: Wakefulness after sleep onset - total number of minutes that a participant is awake after having initially fallen asleep. PSG assessments will be performed on 2 consecutive nights. | At Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in WASO as measured by PSG | WASO: Wakefulness after sleep onset - total number of minutes that a participant is awake after having initially fallen asleep. PSG assessments will be performed on 2 consecutive nights. | At Week 12 | 
| Change from baseline in SE as measured by PSG | SE: Sleep Efficiency - ratio between the total time a participant is asleep (TST) to the total time spent in bed. Presented as a percentage. | At Week 4 | 
| Change from baseline in SE as measured by PSG | SE: Sleep Efficiency - ratio between the total time a participant is asleep (TST) to the total time spent in bed. Presented as a percentage. | At Week 12 | 
| Change from baseline in PROMIS SD SF 8b total score | PROMIS SD SF 8b: Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b. The PROMIS SD SF 8b includes 8 items assessing sleep disturbance over the past 7 days. Items assess sleep quality, sleep depth and restoration associated with sleep, perceived difficulties with getting to sleep or staying asleep and perceptions of the adequacy of and satisfaction with sleep. Participants respond to the items on a 5-point scale from not at all, never or very poor to very much, always or very good. Total scores range from 8 to 40, with higher scores indicating greater severity of sleep disturbance. | At Week 4 | 
| Change from baseline in PROMIS SD SF 8b total score | PROMIS SD SF 8b: Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b. The PROMIS SD SF 8b includes 8 items assessing sleep disturbance over the past 7 days. Items assess sleep quality, sleep depth and restoration associated with sleep, perceived difficulties with getting to sleep or staying asleep and perceptions of the adequacy of and satisfaction with sleep. Participants respond to the items on a 5-point scale from not at all, never or very poor to very much, always or very good. Total scores range from 8 to 40, with higher scores indicating greater severity of sleep disturbance. | At Week 12 | 
| Change from baseline in ISI total score | ISI: Insomnia Severity Index. The ISI is a 7 item instrument that quantifies the participant perception of insomnia severity, along with the impact of insomnia on daytime functioning in adults in the last 2 weeks. The items refer to: severity of sleep onset, sleep maintenance and early morning wakening problems, satisfaction with sleep pattern, noticeability of sleep problems by others, distress caused by the sleep difficulties and interference of sleep difficulties with daytime functioning. It is scored on a 5 point Likert scale from 0 to 4 depending on the item (0=none, 4=very severe (Items 1-3); 0=very satisfied, 4=very dissatisfied (Item 4); 0=not at all noticeable, 4=very much noticeable (Item 5); 0=not at all worried, and 4=very much worried (Item 6); 0=not at all interfering, 4=very much interfering (Item 7)). The scores for each item are summed to produce the total score (maximum 28), higher scores indicates greater severity. | At Week 4 | 
| Change from baseline in ISI total score | ISI: Insomnia Severity Index. The ISI is a 7 item instrument that quantifies the participant perception of insomnia severity, along with the impact of insomnia on daytime functioning in adults in the last 2 weeks. The items refer to: severity of sleep onset, sleep maintenance and early morning wakening problems, satisfaction with sleep pattern, noticeability of sleep problems by others, distress caused by the sleep difficulties and interference of sleep difficulties with daytime functioning. It is scored on a 5 point Likert scale from 0 to 4 depending on the item (0=none, 4=very severe (Items 1-3); 0=very satisfied, 4=very dissatisfied (Item 4); 0=not at all noticeable, 4=very much noticeable (Item 5); 0=not at all worried, and 4=very much worried (Item 6); 0=not at all interfering, 4=very much interfering (Item 7)). The scores for each item are summed to produce the total score (maximum 28), higher scores indicates greater severity. | At Week 12 | 
| Number of participants with Treatment-emergent Adverse Events (TEAEs) |  | Up to 16 weeks | 
| Number of participants with Abnormal laboratory parameters |  | Up to 13 weeks |