A Double-Blind, Randomised, Placebo Controlled, Adaptive Design Study of the Efficacy, Safety and Pharmacokinetics of NT-814 in Female Subjects With Moderate to Severe Vasomotor Symptoms Associated With the Menopause
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 199
- 试验地点
- 25
- 主要终点
- Mean Change From Baseline in Mean Daily Frequency of Moderate and Severe Hot Flushes From Baseline to Week 4
研究概览
简要总结
The purpose of this study is to determine the effectiveness of BAY3427080 (NT-814), taken once a day, in the treatment of troublesome post-menopausal symptoms.
详细描述
This is a multi-centre, multi-country, double-blind, randomised, placebo-controlled Phase 2b study. The study will have a single-blind run-in period and will be adaptive with respect to the number of subjects recruited into each dose group. Four doses of BAY3427080 (40 mg once a day, 80 mg once a day, 120 mg once a day and 160 mg once a day) will be investigated and compared to placebo, in five parallel groups. Subjects will participate in the study for a total of approximately 19 weeks, comprising a screening period of 1 week, a 14 week treatment period, and then a final follow up visit 4 weeks after the end of the treatment period. There will be a total of 8 visits whilst participating in the study. Subjects will record their hot flashes in an electronic diary during the screening period to establish eligibility and throughout the study after randomisation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal
- •Body mass index between 18 and 38 kg/m2, inclusive
- •Subject experiences moderate or severe hot flashes
排除标准
- •Inability to comply with the use of prohibited and allowed medications as described in the protocol.
- •Any prior or ongoing history of clinically relevant drug or alcohol abuse within 12 months of Screening.
- •Any clinically significant prior or ongoing history of arrhythmias, either determined through clinical history or on ECG evaluation.
- •Any clinically significant abnormal laboratory test result(s) measured at Screening.
- •Any active ongoing condition that could have caused difficulty in interpreting vasomotor symptoms.
- •Uncontrolled hypertension.
- •A history or hyperthyroidism, hypothyroidism or abnormal thyroid function tests at Screening. Treated hypothyroidism with normal thyroid function test results at Screening is acceptable.
研究组 & 干预措施
160 mg Elinzanetant (BAY3427080)
Participants received 4x40 mg elinzanetant capsules.
干预措施: Elinzanetant (BAY3427080) (Drug)
120 mg Elinzanetant (BAY3427080)
Participants received 3x40 mg elinzanetant capsules and 1 placebo capsule.
干预措施: Elinzanetant (BAY3427080) (Drug)
80 mg Elinzanetant (BAY3427080)
Participants received 2x40 mg elinzanetant capsules and 2 placebo capsules.
干预措施: Elinzanetant (BAY3427080) (Drug)
40 mg Elinzanetant (BAY3427080)
Participants received one 40 mg elinzanetant capsule and 3 placebo capsules.
干预措施: Elinzanetant (BAY3427080) (Drug)
Placebo
Participants received four placebo capsules orally once daily in the evening before bedtime.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in Mean Daily Frequency of Moderate and Severe Hot Flushes From Baseline to Week 4
时间窗: From baseline to Week 4
Participants recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity.
Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Week 4
时间窗: From baseline to Week 4
Participants recorded daily in their eDiary the frequency and severity of hot flushes during the treatment period. Mean weekly severity = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). Severity is graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe).
Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Week 12
时间窗: From baseline to Week 12
Participants recorded daily in their eDiary the frequency and severity of hot flushes during the treatment period. Mean weekly severity = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). Severity was graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe).
Mean Change From Baseline in Mean Daily Frequency of Moderate and Severe Hot Flushes From Baseline to Week 12
时间窗: From baseline to Week 12
Participants recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity.
次要结局
- Change From Baseline in the Insomnia Severity Index (ISI) Score at Weeks 4, 8, 12 and 16(From baseline to Weeks 4, 8, 12 and 16)
- Mean Change From Baseline in Number of All Night-time Awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16(From baseline to Weeks 1, 2, 4, 8, 12 and 16)
- Change From Baseline in the Hot Flush Related Daily Interference Scale (HFRDIS) Scores at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Vital Signs (Systolic Blood Pressure) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Number of Subjects With Normal Electrocardiogram (ECG) Findings at Each Visit(At Weeks 2, 4, 8, 12 and 16)
- Mean Change From Baseline in Frequency of Mean Daily Moderate and Severe Hot Flushes From Baseline to Weeks 1, 2, 8 and 16(From baseline to Weeks 1, 2, 8 and 16)
- Mean Change From Baseline in Mean Daily Frequency of All Hot Flushes From Baseline to Weeks 1, 2, 4, 8, 12 and 16(From baseline to Weeks 1, 2, 4, 8, 12 and 16)
- Change From Baseline in the Global and Individual Domain Scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16(From baseline to Weeks 4, 8, 12 and 16)
- Change From Baseline in the Menopause-specific Quality-of-Life Questionnaire Intervention Version (MenQoL-I) Scores at Weeks 4, 8, 12 and 16(From baseline to Weeks 4, 8, 12 and 16;)
- Plasma Elinzanetant Concentrations at Weeks 2, 4, 8 ,12(At Weeks 2, 4, 8 ,12)
- Mean Change From Baseline in the Mean Daily Hot Flush Score (Frequency x Severity) at Weeks 1, 2, 4, 8, 12 and 16(From baseline to Weeks 1, 2, 4, 8, 12 and 16)
- Number of Participants With ≥50% and ≥80% Reduction From Baseline in Mean Daily Hot Flushes Frequency at Week 12(Week 12)
- Mean Change From Baseline in Mean Daily Number of NTAs Secondary to Hot Flushes at Weeks 1, 2, 4, 8, 12 and 16(From baseline to Weeks 1, 2, 4, 8, 12 and 16)
- Nature and Severity of Adverse Events(Up to Week 16)
- Number of Subjects With Abnormal Clinically Significant ECG Findings at Each Visit(At Weeks 2, 4, 8, 12 and 16)
- Number of Subjects With Change From Baseline in ECG QTcF Values by Category at Weeks 2, 4, 8, 12 and 16: ≤0, >0 to ≤30, >30 to ≤60, >60 Msec(From baseline to Weeks 2, 4, 8, 12 and 16)
- Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Weeks 1, 2, 8 and 16(From baseline to Weeks 1, 2, 8 and 16)
- Mean Change From Baseline in Mean Severity of All Hot Flushes From Baseline to Weeks 1, 2, 4, 8, 12 and 16(From baseline to Weeks 1, 2, 4, 8, 12 and 16)
- Withdrawals Due to an Adverse Event(Up to Week 16)
- Change From Baseline in Vital Signs (Pulse Rate) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Vital Signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Number of Subjects With Abnormal Not Clinically Significant ECG Findings at Each Visit(At Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QT)(At Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QTc)(At Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in the Beck Depression Inventory II (BDI-II) Scores at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Number of Subjects Used Concomitant Medications(Up to Week 16)
- Change From Baseline in Vital Signs (Diastolic Blood Pressure) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Vital Signs (Temperature) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Vital Signs (Waist Circumference) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QTcF)(At Weeks 2, 4, 8, 12 and 16)
- Number of Subjects With Absolute QTcF Values by Category at Each Visit: ≤450, >450 to ≤480, >480 to ≤500, >500 Msec(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Leukocytes, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Protein and Albumin(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Vital Signs (Weight) at Weeks 2, 4, 8, 12 and 16(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Leukocytes, Platelets, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: pH(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Specific Gravity(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Hyaline Casts(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (RR)(At Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (PR)(At Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) at Weeks 4, 12 and 16(Baseline to Weeks 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 for Clinical Laboratory Parameters Hematology: Hematocrit(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Sodium, Potassium, Glucose, Urea Nitrogen, Calcium, Phosphate, Bicarbonate, Magnesium and Chloride(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Bacteria, Yeast Cells, Granular Casts, RBC Casts, Waxy Casts, WBC Casts, Calcium Oxalate Crystals, Triple Phosphate Crystals and Uric Acid Crystals(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 for Clinical Laboratory Parameters Hematology: Erythrocytes(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Hemoglobin(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 12 and 16 in Clinical Laboratory Parameters Bone: Bone Specific Alkaline Phosphatase and Procollagen 1 N-Terminal Propeptide(From baseline to Weeks 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Erythrocytes Mean Corpuscular Volume(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Creatinine and Bilirubin(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Creatinine Kinase, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase and Gamma Glutamyl Transferase(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Hemoglobin A1C(From baseline to Weeks 2, 4, 8, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Erythrocytes and Leukocytes(From baseline to Weeks 2, 4, 12 and 16)
- Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Glucose, Bilirubin, Ketones, Occult Blood, Protein, Urobilinogen and Nitrite(From baseline to Weeks 2, 4, 12 and 16)