A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (OASIS-2)

Study Overview
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Brief Summary
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Researchers are looking for a better way to treat women who have hot flashes after women have been through the menopause. Hot flashes are caused by the hormonal changes that happen when a woman's body has been through the menopause. Menopause is when women stop having a menstrual cycle, also called a period. During the menopause, the ovaries increasingly produce less sex hormones as a result of the natural ageing process and related hormonal adjustments. The decline in hormone production can lead to various symptoms which, in some cases, can have a very adverse effect on a menopausal woman's quality of life. The study treatment, elinzanetant, was developed to treat symptoms caused by hormonal changes. It works by blocking a protein called neurokinin from sending signals to other parts of the body, which is thought to play a role in starting hot flashes. There are treatments for hot flashes in women who have been through the menopause, but may cause medical problems for some people. In this study, the researchers will learn how well elinzanetant works compared to a placebo in women who have been through the menopause and have hot flashes. A placebo looks like a treatment but does not have any medicine in it. To compare these study treatments, the doctors will ask the participants to record information about the participants' hot flashes in an electronic diary. The researchers will study the number of hot flashes the participants have and how severe the hot flashes are. The researchers will look at the results from before treatment, after 4 weeks, and after 12 weeks of treatment. The participants in this study will take two capsules of either elinzanetant or the placebo once a day. The participants who take elinzanetant will take it for 26 weeks. The participants who take the placebo will take it for 12 weeks and then take elinzanetant for the next 14 weeks. During the study, the participants will visit the site approximately 9 times and perform 1 visit by phone. Each participant will be in the study for approximately 36 weeks. The treatment duration will be 26 weeks. During the study, the participants will: record information about the participants' hot flashes in an electronic diary answer questions about the participants' symptoms The doctors will: check the participants' health take blood samples ask the participants questions about what medicines the participants are taking and if the participants are having adverse events An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if doctors do not think the adverse events might be related to the study treatments.

Official Title
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A Double-blind, Randomized, Placebo-controlled Multicenter Study to Investigate Efficacy and Safety of Elinzanetant for the Treatment of Vasomotor Symptoms Over 26 Weeks in Postmenopausal Women

Conditions
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Vasomotor Symptoms Associated With Menopause, Hot Flashes

Intervention / Treatment
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* Drug: Elinzanetant (BAY3427080)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal, defined as: at least 12 months of spontaneous amenorrhea prior to signing of informed consent, or at least 6 months of spontaneous amenorrhea prior to signing of informed consent with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL and a serum estradiol concentration of < 30 pg/mL, or at least 6 months after hysterectomy at signing of informed consent with serum FSH levels > 40 mIU/mL and a serum estradiol concentration of < 30 pg/mL, or surgical bilateral oophorectomy with or without hysterectomy at least 6 weeks prior to signing of informed consent. Moderate to severe hot flash (HF) associated with the menopause and seeking treatment for this condition. Participant has completed Hot Flash Daily Diary (HFDD) for at least 11 days during the two weeks preceding baseline visit, and participant has recorded at least 50 moderate or severe HF (including night-time HF) over the last 7 days that the HFDD was completed (assessed at the Baseline Visit). Exclusion Criteria: Any clinically significant prior or ongoing history of arrhythmias, heart block and QT prolongation either determined through clinical history or on ECG evaluation. Any active ongoing condition that could cause difficulty in interpreting vasomotor symptoms (VMS) such as: infection that could cause pyrexia, pheochromocytoma, carcinoid syndrome. Current or history (except complete remission for 5 years or more) of any malignancy (except basal and squamous cell skin tumors). Women receiving adjuvant endocrine therapy (e.g. tamoxifen, aromatase inhibitors, GnRH analogues) cannot be enrolled in this study. Uncontrolled or treatment-resistant hypertension. Women with mild hypertension can be included in the study if they are medically cleared prior to study participation. Untreated hyperthyroidism or hypothyroidism. Treated hyperthyroidism with no abnormal increase of thyroid function laboratory parameters and no relevant clinical signs for > 6 months before signing of informed consent is acceptable. Treated hypothyroidism with normal thyroid function test results during screening and a stable (for ≥ 3 months before signing of informed consent) dose of replacement therapy is acceptable. Any unexplained post-menopausal uterine bleeding. Clinically relevant abnormal findings on mammogram. Abnormal liver parameters. Disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer diagnosed based on endometrial biopsy during 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 (BAY3427080)<br>Participants will receive 120 mg elinzanetant orally once daily for 26 weeks. | Drug: Elinzanetant (BAY3427080)<br>* 120 mg elinzanetant orally once daily<br>|
| Placebo Comparator: Placebo + elinzanetant<br>Participants will receive matching placebo orally once daily for 12 weeks, followed by elinzanetant 120 mg for 14 weeks. | Drug: Elinzanetant (BAY3427080)<br>* 120 mg elinzanetant orally once daily<br>Drug: Placebo<br>* Matching placebo orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in frequency of moderate to severe hot flash (HF) from baseline to Week 4 (assessed by hot flash daily diary [HFDD]) |  | Baseline to Week 4 | 
| Mean change in frequency of moderate to severe HF from baseline to Week 12 (assessed by HFDD) |  | Baseline to Week 12 | 
| Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD) |  | Baseline to Week 4 | 
| Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD) |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD) |  | Baseline to Week 1 | 
| Mean change in frequency of moderate to severe HF from baseline over time |  | Baseline to Week 26 | 
| Mean change in patient-reported outcomes measurement information system sleep disturbance short form 8b (PROMIS SD SF 8b) total score from baseline to Week 12 | 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. Four of the items are scored reversely. Total scores range from 8 to 40, with higher scores indicating greater severity of sleep disturbance. | Baseline to Week 12 | 
| Mean change in menopause specific quality of life scale (MENQOL) total score from baseline to Week 12 | The MENQOL questionnaire is comprised of 29 items assessing the presence of menopausal symptoms and the impact of menopause on health-related quality of life over the past week. The items assess four domains of symptoms and functioning: VMS, psychosocial functioning, physical functioning, and sexual functioning. For each item, the participant indicates if they have experienced the symptom (yes/no). If participants select yes, participants rate how bothered they were by the symptom using a six-point verbal descriptor scale, with response options ranging from 0 'not at all bothered' to 6 'extremely bothered'. Based on the individual responses, item scores, domain scores, and a total MENQOL score are calculated. Each score ranges from 1-8, higher scores indicate greater bother. | Baseline to Week 12 | 
| Mean change in Beck depression inventory (BDI-II) total score from baseline to Week 12 | The BDI-II consists of 21 items to assess the severity of depression over the past 2 weeks. Each item is a list of four statements arranged in increasing levels of severity about a particular symptom of depression. Items use a 4-point verbal response scale ranging from 0 (not at all) to 3 (extreme form of each symptom); specific response options are tailored to the aspect of depression being measured in each item. A total score ranging from 0 to 63 is calculated with scores of 0-13 indicating mild minimal range, 14 - 19 mild depression, 20 - 28 indicating moderate and 29 - 63 severe depression (higher score = greater depression). | Baseline to Week 12 | 
| Mean change in BDI-II total score from baseline to Week 26 | The BDI-II consists of 21 items to assess the severity of depression over the past 2 weeks. Each item is a list of four statements arranged in increasing levels of severity about a particular symptom of depression. Items use a 4-point verbal response scale ranging from 0 (not at all) to 3 (extreme form of each symptom); specific response options are tailored to the aspect of depression being measured in each item. A total score ranging from 0 to 63 is calculated with scores of 0-13 indicating mild minimal range, 14 - 19 mild depression, 20 - 28 indicating moderate and 29 - 63 severe depression (higher score = greater depression). | Baseline to Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause