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
Overview
- Phase
- Phase 3
- Intervention
- Elinzanetant (BAY3427080)
- Conditions
- Vasomotor Symptoms Associated With Menopause
- Sponsor
- Bayer
- Enrollment
- 400
- Locations
- 113
- Primary Endpoint
- Mean Change in Frequency of Moderate to Severe HF From Baseline to Week 4 (Assessed by HFDD)
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Elinzanetant (BAY3427080)
Participants will receive 120 mg elinzanetant orally once daily for 26 weeks.
Intervention: Elinzanetant (BAY3427080)
Placebo + elinzanetant
Participants will receive matching placebo orally once daily for 12 weeks, followed by elinzanetant 120 mg for 14 weeks.
Intervention: Elinzanetant (BAY3427080)
Placebo + elinzanetant
Participants will receive matching placebo orally once daily for 12 weeks, followed by elinzanetant 120 mg for 14 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Mean Change in Frequency of Moderate to Severe HF From Baseline to Week 4 (Assessed by HFDD)
Time Frame: From baseline to Week 4
Participants' assessments of HF were recorded electronically twice daily using the sponsor developed Hot Flash Daily Diary (HFDD). The HFDD was completed in the morning after waking up (morning diary) and each evening at bedtime (evening diary) on the hand-held device. The HFDD items assessed the number of mild, moderate, and severe HF experienced during the day and during the night. Mild HF was defined as a "sensation of heat without sweating", moderate HF was defined as a "sensation of heat with sweating, but able to continue activity", and severe HF was defined as a "sensation of heat with sweating, causing cessation (stopping) of activity". The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically, for Week 4, Day 22-28 were used (Day 1 corresponds to start of treatment).
Mean Change in Frequency of Moderate to Severe HF From Baseline to Week 12 (Assessed by HFDD)
Time Frame: From baseline to Week 12
The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically, for Week 12, Day 78-84 were used (Day 1 corresponds to start of treatment).
Mean Change in Severity of Moderate to Severe HF From Baseline to Week 4 (Assessed by HFDD)
Time Frame: From baseline to Week 4
In the HFDD, hot flash (HF) severity is scored as 1=mild, 2=moderate, and 3=severe; a decrease indicates improvement. The diary records the number of mild, moderate, and severe HFs during day and night. Mild HFs are a "sensation of heat without sweating"; moderate are "heat with sweating but able to continue activity"; severe are "heat with sweating that stops activity." Baseline mean daily severity is calculated as: (2×moderateHFs+3×severeHFs)÷(totalmoderate+severeHFs).(2 × moderate HFs + 3 × severe HFs) ÷ (total moderate + severe HFs).(2×moderateHFs+3×severeHFs)÷(totalmoderate+severeHFs). If none occur, severity=0. Weekly severity during treatment is based on available days (Week 4: Days 22-28; Week 12: Days 78-84; Day 1=start of treatment), averaging the mean daily severity for that week. If more than 2 days are missing, the weekly value is set to missing
Mean Change in Severity of Moderate to Severe HF From Baseline to Week 12 (Assessed by HFDD)
Time Frame: From baseline to Week 12
In the HFDD, hot flash (HF) severity is categorized as 1=mild, 2=moderate, 3=severe; thus, a decrease indicates improvement. The HFDD records the number of mild, moderate, and severe HFs during day and night. Mild HFs are a "sensation of heat without sweating"; moderate involve "heat with sweating but able to continue activity"; severe involve "heat with sweating that stops activity." Mean daily severity at baseline is calculated as: (2 × moderate HFs) + (3 × severe HFs)\\\] ÷ (total moderate + severe HFs). If none occur, severity is set to 0. Weekly severity during treatment is based on available days (Week 4: Days 22-28; Week 12: Days 78-84; Day 1=start of treatment), averaging mean daily severity across that week. If more than 2 days are missing, the week is set to missing.
Secondary Outcomes
- Mean Change in Frequency of Moderate to Severe HF From Baseline to Week 1 (Assessed by HFDD)(From baseline to Week 1)
- Mean Change in Frequency of Moderate to Severe HF From Baseline Over Time (Assessed by HFDD)(From baseline to Week 30)
- Mean Change in Patient-reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score From Baseline to Week 12(From baseline to Week 12)
- Mean Change in Menopause-specific Quality of Life Scale (MENQOL) Total Score From Baseline to Week 12(From baseline to Week 12)
- Mean Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to Week 12(From baseline to Week 12)
- Mean Change in BDI-II Total Score From Baseline to Week 26(From baseline to Week 26)