A study to test how effective and safe fezolinetant is in women who have moderate to severe hot flashes due to menopause and who cannot take hormone therapy.
- Conditions
- MedDRA version: 21.0Level: LLTClassification code 10020407Term: Hot flashesSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Hormonal diseases [C19]Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated with Menopause
- Registration Number
- EUCTR2021-001685-38-BG
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 440
1. IRB/IEC approved written informed consent and privacy language as per national regulations must be obtained from the participant prior to any study-related procedures.
2. Participant is born female, aged = 40 years and = 65 years of age at the screening visit
3. Participant must be seeking treatment or relief for VMS associated with menopause and confirmed as menopausal per one of the following criteria at the screening visit:
• Spontaneous amenorrhea for = 12 consecutive months
• Spontaneous amenorrhea for = 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L)
• Had bilateral oophorectomy = 6 weeks prior to the screening visit (with or without hysterectomy)
4. Participant has VMS and is unsuitable to receive HRT (HRT contraindicated, HRT caution, HRT stoppers and HRT averse participants). The definitions for HRT unsuitable categories are provided below:
• HRT Contraindicated: participants with undiagnosed vaginal bleeding, history of breast cancer or estrogen dependent tumors; arterial thromboembolic disease (e.g., angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, venous thrombophilic disorder [e.g., deep vein thrombosis, pulmonary embolism]); hypersensitivity to estrogen and progesterone therapy or any of the excipients; or porphyria. Note: Participants with undiagnosed vaginal bleeding will be allowed in the study after appropriate assessment has been performed at the investigator’s discretion.
• HRT Caution: participants with history of diabetes mellitus, hyperlipidemia, smoking (current), migraine, obesity (body mass index > 29.9 kg/m2), systemic lupus erythematosus, epilepsy, family history of breast cancer in the first degree relative or mutation of breast cancer gene (BRCA1 and BRCA2)
• HRT Stoppers: participants who have discontinued HRT due to lack of efficacy, HRT-related side effects, advised by healthcare provider to stop due to length of time on HRT or due to participant’s age = 60 years old
• HRT Averse: participants who made an informed choice to not take HRT after a consultation about the benefit risks of HRT
For HRT Contraindicated and HRT Caution participants, written documentation regarding the conditions listed must be present in the medical files of participants to qualify under these definitions. For HRT Stoppers for lack of efficacy and HRT-related side effects, accurate and exhaustive documentation must be provided, for example (and as applicable) length of HRT treatment and reason for determining inefficacy, type and duration of HRT-related side effects, etc. For HRT Averse participants, documentation must be provided regarding the nature and extent of the participant’s consultation with her healthcare provider, participant’s reason not to take HRT, etc.
5. Participant has a minimum average of 7 moderate to severe HFs (VMS) per day as recorded in the electronic diary during the last 10 days prior to randomization.
6. Participant is in good general health as determined on the basis of medical history, general physical examination, laboratory and other medical assessments in the opinion of the investigator.
7. Participant has a negative serology panel (including hepatitis B surface antigen, hepatitis C virus antibody and human immunodeficiency virus antibody screens).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 440
F.1.3 E
1. Participant uses a prohibited therapy for VMS (e.g., prescription, over-the-counter or herbal) as described in [Section 6.8 Concomitant Therapy] prior to screening and for the duration of treatment with IP.
2. Participant has known documented substance abuse or alcohol addiction within 6 months of screening.
3. Participant has history of a malignant tumor within the last 5 years, except for basal cell carcinoma.
4. 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 in the opinion of the investigator.
5. Participant has history of severe allergy, hypersensitivity or intolerance to the IP and/or any of its excipients.
6. Participant has a history of seizures or other convulsive disorders unless well controlled.
7. 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 in the opinion of the investigator.
8. Participant has active liver disease, jaundice, elevated liver aminotransferases at screening (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total bilirubin (TBL) or direct bilirubin (DBL), elevated International Normalized Ratio (INR) or elevated alkaline phosphatase (ALP). Participants with mildly elevated ALT or AST up to 1.5 × upper limit of normal (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.
9. 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 m2 at the screening visit.
10. Participant has a history of suicide attempt or suicidal behavior within the last 12 months.
11. Participant is participating concurrently in another interventional study.
12. Participant who has been previously enrolled in a clinical study with fezolinetant.
13. Participant is unable or unwilling to complete the study procedures.
14. Participant has any condition, which in the investigator’s opinion, makes the participant unsuitable for study participation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of fezolinetant 45 mg versus placebo on the frequency of moderate to severe VMS;Secondary Objective: Key secondary: - To evaluate the efficacy of fezolinetant 45 mg versus placebo on the severity of moderate to severe VMS;<br>Secondary: - To evaluate the effect of fezolinetant 45 mg versus placebo on patient-reported sleep disturbance<br>- To evaluate the efficacy of fezolinetant 45 mg versus placebo on the frequency and severity of moderate to severe VMS<br>- To evaluate the safety and tolerability of fezolinetant 45 mg;Primary end point(s): - Mean change in the frequency of moderate to severe Vasomotor Symptoms (VMS) from baseline to week 24;Timepoint(s) of evaluation of this end point: ?Baseline to week 24.
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: ?Up to week 27<br>;Secondary end point(s): - Mean change in the severity of moderate to severe VMS from baseline to week 24;<br>- 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 to week 24;<br>- Mean change in the frequency of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20;<br>- Mean change in the severity of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20;<br>- Mean percent change in the frequency of moderate and severe VMS from baseline to weeks 1, 4, 8, 12, 16, 20 and 24;<br>- Responder of percent reduction = 50%, = 75% and at 100% in the frequency of moderate and severe VMS from baseline to weeks 1, 4, 8, 12, 16, 20 and 24;<br>- Frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory assessments, vital signs and electrocardiogram (ECG);<br>