Sleep Disturbances Associated With Menopause
Conditions
Brief summary
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.
Interventions
DRUGElinzanetant
Oral
OTHERPlacebo
Oral
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Wakefulness After Sleep Onset (WASO) at Week 4 as Measured by Polysomnography (PSG) | From baseline until week 4 | WASO is defined as total time (min) spent awake from onset of persistent sleep to lights on. Persistent sleep is defined as 20 consecutive epochs (10 min) of non wakefulness. Smaller WASO values indicate shorter periods of wakefulness after sleep onset. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sleep Efficiency (SE) at Week 4 as Measured by PSG | From baseline to Week 4 | Sleep efficiency is defined as the percentage of time spent asleep while in bed. (Total sleep time / time in bed) x 100. Higher sleep efficiency values indicate more time spent asleep. |
| Change From Baseline in SE at Week 12 as Measured by PSG | From baseline to week 12 | Sleep efficiency is defined as the percentage of time spent asleep while in bed. (Total sleep time / time in bed) x 100. Higher sleep efficiency values indicate more time spent asleep. |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 4 | From baseline until week 4 | Participants' responses to the 8 items of the instrument are scored on a 1-5 numeric rating scale and will be aggregated to derive total raw scores ranging from 8-40 with higher scores indicating greater severity of sleep disturbance. These total raw scores will be converted into T-scores for comparison with population norms (United States general population). T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population. |
| Change From Baseline in WASO at Week 12 as Measured by PSG | From baseline until week 12 | WASO is defined as total time (min) spent awake from onset of persistent sleep to lights on. Persistent sleep is defined as 20 consecutive epochs (10 min) of non wakefulness. Smaller WASO values indicate shorter periods of wakefulness after sleep onset. |
| Change From Baseline in Insomnia Severity Index (ISI) Total Score at Week 4 | From baseline until week 4 | Insomnia Severity Index (ISI): The ISI is a 7-item tool that measures insomnia severity over the past two weeks (Bastien et al., 2001). It evaluates sleep onset, maintenance issues, early morning awakenings, satisfaction with sleep, noticeability of problems, distress caused, and daytime interference. Scoring: The ISI uses a 5-point Likert scale (0 to 4). Item scores are summed to yield a total score ranging from 0 to 28. Severity Categories: 0-7: No clinically significant insomnia (better outcome) 8-14: Subthreshold insomnia (moderate outcome) 15-21: Clinical insomnia (moderate severity) (worse outcome) 22-28: Clinical insomnia (severe) (worse outcome) Interpretation: Higher total scores indicate worse insomnia severity, while lower scores indicate better sleep quality. The total score is the sum of individual item scores. |
| Change From Baseline in ISI Total Score at Week 12 | From baseline until week 12 | Insomnia Severity Index (ISI): The ISI is a 7-item tool that measures insomnia severity over the past two weeks (Bastien et al., 2001). It evaluates sleep onset, maintenance issues, early morning awakenings, satisfaction with sleep, noticeability of problems, distress caused, and daytime interference. Scoring: The ISI uses a 5-point Likert scale (0 to 4). Item scores are summed to yield a total score ranging from 0 to 28. Severity Categories: 0-7: No clinically significant insomnia (better outcome) 8-14: Subthreshold insomnia (moderate outcome) 15-21: Clinical insomnia (moderate severity) (worse outcome) 22-28: Clinical insomnia (severe) (worse outcome) Interpretation: Higher total scores indicate worse insomnia severity, while lower scores indicate better sleep quality. The total score is the sum of individual item scores. |
| Change From Baseline inPatient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 12 | From baseline until week 12 | Participants' responses to the 8 items of the instrument are scored on a 1-5 numeric rating scale and will be aggregated to derive total raw scores ranging from 8-40 with higher scores indicating greater severity of sleep disturbance. These total raw scores will be converted into T-scores for comparison with population norms (United States general population). T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population. |
Countries
Austria, Belgium, Czechia, Germany, Poland, Spain, United States
Participant flow
Recruitment details
The study was conducted at 39 study centers, of which 30 centers had randomized participants in Europe and the US. In the US, separate sleep laboratories were used by 9 sites that did not have polysomnography (PSG) capability.
Pre-assignment details
Out of the 338 screened participants, 110 were randomized and received treatment, and 103 participants completed the study. Among the 228 participants who did not proceed to randomization, screening failure was the primary reason (223 participants).
Participants by arm
| Arm | Count |
|---|---|
| Elinzanetant 120 mg (2x 60 mg soft gel capsules) of elinzanetant orally once daily for 12 weeks | 55 |
| Placebo 2 soft gel capsules orally once daily for 12 weeks | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Subject took an out of state job and had to early terminate | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Elinzanetant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 4.6 | 54.9 Years STANDARD_DEVIATION 4.7 | 54.8 Years STANDARD_DEVIATION 4.6 |
| Alcohol consumption Abstinent | 14 Participants | 25 Participants | 39 Participants |
| Alcohol consumption Light | 41 Participants | 30 Participants | 71 Participants |
| Average weekly frequency of moderate to severe HF >=35 - <50 moderate to severe HF per week | 11 Participants | 13 Participants | 24 Participants |
| Average weekly frequency of moderate to severe HF <35 moderate to severe HF per week | 13 Participants | 11 Participants | 24 Participants |
| Average weekly frequency of moderate to severe HF >=50 moderate to severe HF per week | 31 Participants | 31 Participants | 62 Participants |
| Body Mass Index (kg/m2) | 27.97 Kilogram per square meter STANDARD_DEVIATION 4.36 | 27.63 Kilogram per square meter STANDARD_DEVIATION 3.75 | 27.80 Kilogram per square meter STANDARD_DEVIATION 4.05 |
| Caffeine consumption (mg) per day | 142.07 Miligrams STANDARD_DEVIATION 129.87 | 119.79 Miligrams STANDARD_DEVIATION 99.53 | 131.43 Miligrams STANDARD_DEVIATION 116.26 |
| Height (cm) | 164.64 Centimeters STANDARD_DEVIATION 7.08 | 164.18 Centimeters STANDARD_DEVIATION 7.01 | 164.41 Centimeters STANDARD_DEVIATION 7.02 |
| Level of education Attending college | 5 Participants | 3 Participants | 8 Participants |
| Level of education College or university education | 32 Participants | 34 Participants | 66 Participants |
| Level of education Missing | 1 Participants | 0 Participants | 1 Participants |
| Level of education Other | 14 Participants | 10 Participants | 24 Participants |
| Level of education Professional certification | 3 Participants | 8 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 40 Participants | 45 Participants | 85 Participants |
| Sex/Gender, Customized Female | 55 Participants | 55 Participants | 110 Participants |
| Smoking Current | 10 Participants | 3 Participants | 13 Participants |
| Smoking Former | 5 Participants | 10 Participants | 15 Participants |
| Smoking Never | 40 Participants | 42 Participants | 82 Participants |
| Weight (kg) | 75.77 Kilograms STANDARD_DEVIATION 12.45 | 74.41 Kilograms STANDARD_DEVIATION 10.61 | 75.09 Kilograms STANDARD_DEVIATION 11.53 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 24 / 55 | 25 / 55 |
| serious Total, serious adverse events | 0 / 55 | 2 / 55 |
Outcome results
Primary
Change From Baseline in Wakefulness After Sleep Onset (WASO) at Week 4 as Measured by Polysomnography (PSG)
WASO is defined as total time (min) spent awake from onset of persistent sleep to lights on. Persistent sleep is defined as 20 consecutive epochs (10 min) of non wakefulness. Smaller WASO values indicate shorter periods of wakefulness after sleep onset.
Time frame: From baseline until week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in Wakefulness After Sleep Onset (WASO) at Week 4 as Measured by Polysomnography (PSG) | -23.50 Minutes | Standard Error 4.63 |
| Placebo | Change From Baseline in Wakefulness After Sleep Onset (WASO) at Week 4 as Measured by Polysomnography (PSG) | -1.01 Minutes | Standard Error 4.68 |
Secondary
Change From Baseline in Insomnia Severity Index (ISI) Total Score at Week 4
Insomnia Severity Index (ISI): The ISI is a 7-item tool that measures insomnia severity over the past two weeks (Bastien et al., 2001). It evaluates sleep onset, maintenance issues, early morning awakenings, satisfaction with sleep, noticeability of problems, distress caused, and daytime interference. Scoring: The ISI uses a 5-point Likert scale (0 to 4). Item scores are summed to yield a total score ranging from 0 to 28. Severity Categories: 0-7: No clinically significant insomnia (better outcome) 8-14: Subthreshold insomnia (moderate outcome) 15-21: Clinical insomnia (moderate severity) (worse outcome) 22-28: Clinical insomnia (severe) (worse outcome) Interpretation: Higher total scores indicate worse insomnia severity, while lower scores indicate better sleep quality. The total score is the sum of individual item scores.
Time frame: From baseline until week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in Insomnia Severity Index (ISI) Total Score at Week 4 | -7.8 Scores on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Insomnia Severity Index (ISI) Total Score at Week 4 | -4.7 Scores on a scale | Standard Deviation 4.8 |
Secondary
Change From Baseline in ISI Total Score at Week 12
Insomnia Severity Index (ISI): The ISI is a 7-item tool that measures insomnia severity over the past two weeks (Bastien et al., 2001). It evaluates sleep onset, maintenance issues, early morning awakenings, satisfaction with sleep, noticeability of problems, distress caused, and daytime interference. Scoring: The ISI uses a 5-point Likert scale (0 to 4). Item scores are summed to yield a total score ranging from 0 to 28. Severity Categories: 0-7: No clinically significant insomnia (better outcome) 8-14: Subthreshold insomnia (moderate outcome) 15-21: Clinical insomnia (moderate severity) (worse outcome) 22-28: Clinical insomnia (severe) (worse outcome) Interpretation: Higher total scores indicate worse insomnia severity, while lower scores indicate better sleep quality. The total score is the sum of individual item scores.
Time frame: From baseline until week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in ISI Total Score at Week 12 | -9.8 ISI total score | Standard Deviation 6.4 |
| Placebo | Change From Baseline in ISI Total Score at Week 12 | -6.9 ISI total score | Standard Deviation 5.6 |
Secondary
Change From Baseline inPatient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 12
Participants' responses to the 8 items of the instrument are scored on a 1-5 numeric rating scale and will be aggregated to derive total raw scores ranging from 8-40 with higher scores indicating greater severity of sleep disturbance. These total raw scores will be converted into T-scores for comparison with population norms (United States general population). T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population.
Time frame: From baseline until week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline inPatient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 12 | -14.66 T-Score | Standard Deviation 9.36 |
| Placebo | Change From Baseline inPatient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 12 | -6.65 T-Score | Standard Deviation 8.29 |
Secondary
Change From Baseline in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 4
Participants' responses to the 8 items of the instrument are scored on a 1-5 numeric rating scale and will be aggregated to derive total raw scores ranging from 8-40 with higher scores indicating greater severity of sleep disturbance. These total raw scores will be converted into T-scores for comparison with population norms (United States general population). T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population.
Time frame: From baseline until week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 4 | -11.17 T-Score | Standard Deviation 8.04 |
| Placebo | Change From Baseline in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) Total T-score at Week 4 | -6.59 T-Score | Standard Deviation 6.76 |
Secondary
Change From Baseline in SE at Week 12 as Measured by PSG
Sleep efficiency is defined as the percentage of time spent asleep while in bed. (Total sleep time / time in bed) x 100. Higher sleep efficiency values indicate more time spent asleep.
Time frame: From baseline to week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in SE at Week 12 as Measured by PSG | 5.15 Percentage | Standard Deviation 9.68 |
| Placebo | Change From Baseline in SE at Week 12 as Measured by PSG | 4.67 Percentage | Standard Deviation 8.1 |
Secondary
Change From Baseline in Sleep Efficiency (SE) at Week 4 as Measured by PSG
Sleep efficiency is defined as the percentage of time spent asleep while in bed. (Total sleep time / time in bed) x 100. Higher sleep efficiency values indicate more time spent asleep.
Time frame: From baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in Sleep Efficiency (SE) at Week 4 as Measured by PSG | 6.85 Percentage | Standard Deviation 8.07 |
| Placebo | Change From Baseline in Sleep Efficiency (SE) at Week 4 as Measured by PSG | 1.13 Percentage | Standard Deviation 10.31 |
Secondary
Change From Baseline in WASO at Week 12 as Measured by PSG
WASO is defined as total time (min) spent awake from onset of persistent sleep to lights on. Persistent sleep is defined as 20 consecutive epochs (10 min) of non wakefulness. Smaller WASO values indicate shorter periods of wakefulness after sleep onset.
Time frame: From baseline until week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elinzanetant | Change From Baseline in WASO at Week 12 as Measured by PSG | -16.48 Minutes | Standard Error 4.64 |
| Placebo | Change From Baseline in WASO at Week 12 as Measured by PSG | -15.54 Minutes | Standard Error 4.76 |