Vasomotor Symptoms (Hot Flashes) Associated with Menopause MedDRA version: 21.0 Level: LLT Classification code 10020407 Term: Hot flashes System Organ Class: 100000004866
Conditions
Sponsors
Astellas Pharma Global Development, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is born female, aged = 40 years and = 65 years of age at the screening visit. 3. Subject has a body mass index between =18 kg/m2 and = 38 kg/m2. 4. Subject must be seeking treatment or relief for VMS associated with menopause and confirmed as menopausal per 1 of the following criteria at the screening visit: ? Spontaneous amenorrhea for >= 12 consecutive months ? Spontaneous amenorrhea for >= 6 months with biochemical criteria of menopause (FSH> 40 IU/L), or ? Having had bilateral oophorectomy >= 6 weeks prior to the screening visit. 5. Subject is seeking treatment for relief for VMS associated with menopause. 6. Subject is in good general health as determined on the basis of medical history and general physical examination, including a bimanual clinical pelvic examination and clinical breast examination devoid of relevant clinical findings, performed at the screening visit; hematology and biochemistry parameters; pulse rate and/or blood pressure; and ECG within the reference range for the population studied, or showing no clinically relevant deviations, as judged by the investigator. 7. Subject has documentation of a normal/negative or no clinically significant mammogram findings (obtained at screening or within the prior 12 months of trial enrollment). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic findings. 8. Subject is willing to undergo a TVU to evaluate the uterus and ovaries at screening and at week 52 (EOT). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the ED visit. 9. Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT) or the ED visit for subjects who are withdrawn from the study prior to completion, and any time during the study in the case of uterine bleeding. The endometrial biopsy obtained at screening must be considered evaulable. 10. Subject has documentation of a normal or not clinically significant Pap test (or equivalent cervical cytology) in the opinion of the investigator within the previous 12 months or at screening. 11. Subject has a negative urine pregnancy test at screening. 12. Subject has a negative serology panel (i.e., negative hepatitis B surface antigen, negative hepatitis C virus antibody and negative human immunodeficiency virus antibody screens) at screening. 13. Subject agrees not to participate in another interventional study while participating in the present study. 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 1740 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject uses a prohibited therapy (strong or moderate cytochrome P450 [CYP] 1A2 inhibitors, hormone replacement therapy [HRT], hormonal contraceptive, any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue such drugs for the full extent of the study. 2. Subject has a known substance abuse or alcohol addiction within 6 months of screening, as assessed by investigator. 3. Subject has previous or current history of a malignant tumor, except for basal cell carcinoma. 4. Subject has hypertension defined as systolic blood pressure = 130mmHg or diastolic blood pressure as = 80 mmHg based on an average of 2 to 3 readings at screening and randomization. Subjects with a medical history with hypertension who are well controlled may be enrolled at the discretion of the investigator. 5. Subject has a history of severe allergy, hypersensitivity or intolerance to drugs in general, including the study drug and any of its excipients. 6. Subject has an unacceptable result from the TVU assessment at screening, i.e., full length of endometrial cavity cannot be visualized or presence of a clinically significant finding. 7. Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyperplasia, endometrial cancer or other clinically significant findings in the opinion of the investigator at screening. 8. Subject has a history within the last 6 months of undiagnosed uterine bleeding. 9. Subject has a history of seizures or other convulsive disorders. 10. Subject has a medical condition or chronic disease (including history of neurological [including cognitive], hepatic, 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. 11. Subject has active liver disease, jaundice or elevated liver aminotransferases (ALT or AST), elevated total or direct bilirubin (DBL), elevated International Normalized Ratio (INR), or elevated alkaline phosphatase (ALP). Patients with mildly elevated ALT or AST up to 1.5 x 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. 13. Subject has a history of suicide attempt or suicidal behavior within the last 12 months or has suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale [CSSRS], or who is at significant risk to commit suicide, as assessed by the investigator at screening and at the time of visit 2 (randomization). 20. Subject has had a partial or full hysterectomy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: ? This end point is the overall frequency and severity of AEs over the full course of the study. AEs are evaluated at each visit but it will be the frequency across the full 12 month study that will be evaluated for the primary endpoint. ?Subjects with endometrial hyperplasia and subjects with endometrial cancer will be evaluated at each visit. ;Main Objective: -To evaluate the effect of fezolinetant on the long-term safety and tolerability in women seeking treatment for relief of Vasomotor Symptoms (VMS) associated with menopause. - To evaluate the effect of fezolinetant on endometrial health after longterm treatment in women seeking treatment for relief of VMS associated with menopause. ;Secondary Objective: To evaluate the effect of fezolinetant on bone mineral density after long-term treatment in women seeking treatment for relief of VMS associated with menopause. ;Primary end point(s): Safety endpoint: ? Frequency and severity of AEs ? Percentage of subjects with endometrial hyperplasia. ? Percentage of subjects with endometrial cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Change from baseline in endometrial thickness at 12 months. ? Percentage of subjects with disordered proliferative endometrium. ? Change from baseline in bone mass density (BMD) and trabecular bone score (TBS) hip and spine at 12 months. ? Vital signs: sitting systolic and diastolic blood pressure and pulse rate. ? Laboratory tests: hematology, biochemistry and urinalysis. ? C-SSRS. ? ECG parameters. ;Timepoint(s) of evaluation of this end point: Endometrial thickness and BMD/TBS assessments are done at baseline and EOT/12 months. Other secondary points are evaluated at each visit. | — |
Countries
Canada, Czech Republic, Hungary, Latvia, Poland, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactService Desk
Astellas Pharma Europe B.V. – Global Development Operations
Outcome results
None listed