A Phase 3b, Randomized, Double-blind, Placebo-controlled, 24-week Study to Assess the Efficacy and Safety of Fezolinetant in Menopausal Women Suffering From Moderate to Severe Vasomotor Symptoms (Hot Flashes) and Considered Unsuitable for Hormone Replacement Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 69
- 主要终点
- Mean change in the frequency of moderate to severe VMS from baseline at week 24
研究概览
简要总结
This study is for women in menopause who have moderate to severe hot flashes. It is for women who are unable to use hormone replacement therapy (HRT). Menopause, a normal part of life, is the time after a woman's last period. Hot flashes often occur during menopause. They can disrupt a woman's daily life.
The study medicines (also called investigational products, or IP) are tablets of fezolinetant or placebo. An investigational product means that the product is not yet licensed. In this study, a placebo is a dummy treatment that looks like fezolinetant but does not have any medicine in it. The study will compare fezolinetant with the placebo to learn if fezolinetant reduces the number and severity of hot flashes.
Women that want to take part in the study will be given an electronic handheld device with an app to track their hot flashes. Some women may be able to use the app on their own smartphone. In the last 10 days before their next clinic visit, the women will record information about their hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. Women will be picked for 1 of 2 treatments (fezolinetant or placebo) by chance alone.
Women who take part in the study will take 2 tablets every day for 24 weeks. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study medicines (fezolinetant or placebo). The women will continue recording information about their hot flashes on the electronic device or their phone. They will also use another device to answer questions about how hot flashes affect their daily life.
During the study, the women will visit their study clinic several times for a check-up. This will happen during Weeks 2, 4, 8, 12, 16, 20, 24, and 27. Some women may be able to have home visits instead, from Week 2 to Week 20. At the check-up, they will be asked if they have any medical problems. Other checks will include vital signs (heart rate, temperature and blood pressure) and some blood samples taken for laboratory tests. At some check-ups, the women will have a physical exam. In Week 2 and Week 24, the women will have an ECG to check their heart rhythm. Women who have a uterus will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs.
The last check-up (at Week 27) will be 3 weeks after they take their last tablets of study medicine (fezolinetant or placebo).
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
- Double (Participant, Investigator)
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
- 未提供
排除标准
- •Participant uses a prohibited therapy for VMS (e.g., prescription, over-the-counter or herbal) prior to screening and for the duration of treatment with investigational product (IP).
- •Participant has known documented substance abuse or alcohol addiction within 6 months of screening.
- •Participant has history of a malignant tumor within the last 5 years, except for basal cell carcinoma.
- •Participant has endometrial thickness > 8 mm on the locally read screening transvaginal ultrasound (TVU) or any clinically significant findings that that would make the participant ineligible.
- •Participant has history of severe allergy, hypersensitivity or intolerance to the IP and/or any of its excipients.
- •Participant has a history of seizures or other convulsive disorders unless well controlled.
- •Participant has a medical condition or chronic disease (including history of neurological [including cognitive], renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine or gynecological disease) or malignancy that could confound interpretation of the study outcome.
- •Participant has any of the following: active liver disease, jaundice, elevated liver aminotransferases at screening (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total bilirubin (TBL) or direct bilirubin (DBL) > 1.5 × upper limit of normal (ULN), elevated International Normalized Ratio (INR) > 1.5 (unless participant is receiving anticoagulant therapy) or elevated alkaline phosphatase (ALP). Participants with mildly elevated ALT or AST up to 1.5 × ULN can be enrolled if TBL and DBL are normal. Participants with mildly elevated ALP (up to 1.5 × ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participants with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
- •Participant has creatinine > 1.5 × ULN or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula <= 59 mL/min per 1.73 m^2 at the screening visit.
- •Participant has a history of suicide attempt or suicidal behavior within the last 12 months.
- •Participant has participated in another interventional study within the last 30 days prior to screening and for the duration of the study.
- •Participant who has been previously enrolled in a clinical study with fezolinetant.
- •Participant is unable or unwilling to complete the study procedures.
- •Participant has any condition makes the participant unsuitable for study participation.
研究组 & 干预措施
fezolinetant
Participants receive fezolinetant 45 milligrams (mg) (one 30 mg tablet and one 15 mg tablet) orally once daily for 24 weeks of treatment.
干预措施: fezolinetant (Drug)
placebo
Participants receive placebo matched to fezolinetant tablets orally once daily for 24 weeks of treatment.
干预措施: placebo (Drug)
结局指标
主要结局
Mean change in the frequency of moderate to severe VMS from baseline at week 24
时间窗: Baseline, week 24
The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.
次要结局
- Mean change in severity of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20(Baseline, weeks 1, 4, 8, 12, 16 and 20)
- Mean percent change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24(Baseline, weeks 1, 4, 8, 12, 16, 20 and 24)
- Mean change in the severity of moderate to severe VMS from baseline at week 24(Baseline, week 24)
- Mean change in the patient-reported sleep disturbance by the Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b total score) from baseline at week 24(Baseline, week 24)
- Mean change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20(Baseline, weeks 1, 4, 8, 12, 16 and 20)
- Number of participants with percent reduction of >/= 50% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24(Baseline, weeks 1, 4, 8, 12, 16, 20 and 24)
- Number of participants with percent reduction of >/= 75% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24(Baseline, weeks 1, 4, 8, 12, 16, 20 and 24)
- Number of participants with percent reduction at 100% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24(Baseline, weeks 1, 4, 8, 12, 16, 20 and 24)
- Number of participants with Treatment Emergent Adverse Events (TEAEs)(From first dose to week 27)