hot flashes Hot Flashes Vasomotor Symptoms
Conditions
Interventions
None listed
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 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 = 12 consecutive months • Spontaneous amenorrhea for >= 6 months with biochemical criterion of menopause (follicle-stimulating hormone [FSH] > 40 IU/L) • Had bilateral oophorectomy >= 6 weeks prior to the screening visit (with or without hysterectomy) • Had hysterectomy without oophorectomy and who meets the biochemical criterion of menopause (FSH > 40 IU/L) 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 negati
Exclusion criteria
Exclusion criteria: 1. 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 IP. Refer to [Section 6.8 Concomitant Therapy and Section 10.4 Appendix 4: List of Excluded Concomitant Medications] for a list of prohibited therapies. 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 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 x 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. 9. Participant has creatinine > 1.5 × ULN or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: Mean change in the frequency of moderate to severe VMS from baseline to week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Mean change in the severity of moderate to severe VMS from baseline to week 24 Secondary Mean change in the participant-reported sleep disturbance by the PROMIS SD SF 8b from baseline to week 24 • Mean change in the frequency of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20 • Mean change in the severity of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20 • Mean percent reduction in the frequency of moderate and severe VMS from baseline to weeks 1, 4, 8, 12, 16, 20 and 24 • 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 • Frequency and severity of AEs, clinical laboratory assessments, vital signs and ECG Exploratory • Change in serum concentrations of sex hormones and SHBG from baseline to weeks 12 and 24 • Plasma concentration of fezolinetant and ES259564 • Mean change in the PROMIS SD SF 8b from baseline to week 4, 12, and 16 • Score on the PGI-S SD at each visit (weeks 4, 12, 16, and 24) • Score on the PGI-C SD to each visit (weeks 4, 12, 16, and 24) • Score on the PGI-C in VMS to at each visit (4, 12, 16, and 24) • Mean change on the MENQOL total score from baseline to weeks 4, 12, 16, and 24 • Mean change on the MENQOL domain scores from baseline to weeks 4, 12, 16, and 24 • Mean change on the Euro-Qol 5D-5L (EQ-5D-5L) Visual Analog Scale (VAS) from baseline to weeks 4, 12, 16, and 24 • Mean change on the WPAI-VMS domain scores from baseline to each week up to weeks 4, 12, 16, and 24 • Mean change on the FSFI total score from baseline to weeks 4, 12, 16, and 24 • Mean change on the FSFI domain scores from baseline to weeks 4, 12, 16, and 24 • Mean change on PHQ-4 score from baseline to weeks 4, 12, 16, and 24 • Mean change in the frequency of mild, moderate and severe VMS from baseline to each week up to week 24 • Mean change in the severity of mild, moderate and sever | — |
Countries
Netherlands
Outcome results
None listed