A Study to Assess the Safety and Tolerability of Fezolinetant in Women Seeking Treatment for Relief of Vasomotor Symptoms (VMS) Associated With Menopause (Moonlight 3)

This is an interventional treatment trial for Hot Flashes focused on measuring Vasomotor Symptoms, menopause, fezolinetant, ESN364 Read More

Inclusion Criteria:

• Subject has a body mass index ≥ 16 kg/m^2 and ≤ 38 kg/m^2 at the screening visit.
• Subject confirmed as menopausal per 1 of the following criteria at the screening visit:

O Subject has spontaneous amenorrhea for >= 12 consecutive months O Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 International Units per Liter [IU/L], or O Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit (with or without hysterectomy).

O FSH > 40 IU/L if subjects received hysterectomy but still have ovary

• Subject is seeking treatment for relief for VMS associated with menopause.
• 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.
• Subject has documentation of a normal/negative or no clinically significant abnormal findings on mammogram (or echo) (e.g., <BI-RADS class 4; obtained at screening or within the prior 12 months of screening). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant abnormal findings.
• Subject is willing to undergo a transvaginal ultrasound (TVU) to evaluate the uterus and ovaries at screening and at week 52 (end of treatment). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit. This is not required for subjects who have had a partial (supra-cervical) or full hysterectomy.
• Subject is willing to undergo an endometrial biopsy at screening and at week 52 (end of treatment) or the ED visit if endometrial thickness > 4 millimeter (mm) indicated by TVU; and subject is willing to undergo an endometrial biopsy at any time during the study in the case of uterine bleeding. This is not required for subjects who have had a partial (supra-cervical) or full hysterectomy. A biopsy with insufficient material for evaluation, or unevaluable material, is acceptable provided the endometrial thickness is no greater than 8 mm.
• Subject has documentation of a normal or not clinically significant abnormal Papanicolaou (Pap) test (or equivalent cervical cytology) within the previous 12 months of screening or at screening. This is not required for subjects who have had a full hysterectomy.
• Subject has a negative urine pregnancy test at screening.
• Subject has a negative serology panel (including hepatitis B virus surface antigen [HBs] and hepatitis C virus antibody [anti-HCV], and human immunodeficiency virus [HIV]) at screening.
• Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

• Subject uses a prohibited therapy (strong and 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.
• Subject has a known substance abuse or alcohol addiction within 6 months of screening.
• Subject has a history of a malignant tumor, except for non-metastatic basal cell carcinoma of the skin.
• Subject has uncontrolled hypertension, defined as systolic blood pressure >= 140 millimeters of mercury (mmHg) or diastolic blood pressure as >= 90 mmHg based on an average of 2 to 3 readings within the screening period.

O Subjects with a medical history of hypertension who are well controlled may be enrolled.

O Subjects who do not meet the criteria may, be re-assessed after initiation or review of antihypertensive measures.

• Subject has a history of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients.
• For subjects with a uterus: 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 abnormal finding.
• For subjects with an endometrial thickness > 4 mm as indicated by TVU at screening: Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyperplasia, endometrial cancer, or other clinically significant abnormal findings in the at screening. A biopsy with insufficient material for evaluation, or unevaluable material is acceptable provided the endometrial thickness is no greater than 8 mm.
• Subject has a history of an undiagnosed uterine bleeding within the last 6 months of screening.
• Subject has a history of seizures or other convulsive disorders.
• 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.
• Subject has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total or direct bilirubin, elevated international normalized ratio (INR), or elevated alkaline phosphatase (ALP) at screening. Subject with mildly elevated ALT or AST up to 1.5 × the upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Subject 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. Subject with Gilbert's syndrome with elevated total bilirubin (TBL) may be enrolled as long as hemolysis is ruled out (i.e., direct bilirubin (DBL), hemoglobin and reticulocytes are normal).
• Subject has creatinine > 1.5 × ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula <= 59 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at the screening visit.
• Subject has a history of suicide attempt or suicidal behavior within the prior to 12 months of study enrollment or has suicidal ideation within the prior to 12 months of study enrollment (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the C-SSRS), or who is at significant risk to commit suicide at screening and at visit 2.
• Subject has previously been enrolled in a clinical trial with fezolinetant.
• Subject has received an investigational study drug within 28 days or 5 half-lives, whichever is longer, prior to screening.
• Subject is unable or unwilling to complete the study procedures.
• Subject has any condition which, makes the subject unsuitable for study participation.