A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause (Skylight 4)

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

Inclusion Criteria:

• Subject has a body mass index ≥ 18 kg/m^2 and ≤ 38 kg/m^2.

• Subject must be seeking treatment or relief for vasomotor symptoms (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 (follicle stimulating hormone > 40 IU/L), or
  • Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
• 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 mammogram findings (obtained at screening or within the prior 12 months of study enrollment). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic 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 (EOT). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit.
• 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is willing to undergo an endometrial biopsy at screening and at week 52 (EOT) or the ED visit for subjects who are withdrawn from the study prior to completion, and any time during the study in the case of uterine bleeding.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 evaluable.
• Subject has documentation of a normal or not clinically significant Papanicolaou (Pap) test (or equivalent cervical cytology) within the previous 12 months or at screening.
• Subject has a negative urine pregnancy test at screening.
• 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.
• Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

• 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.
• Subject has a known substance abuse or alcohol addiction within 6 months of screening.
• Subject has previous or current history of a malignant tumor, except for basal cell carcinoma.

• Subject's systolic blood pressure is ≥ 130 mmHg or diastolic blood pressure is ≥ 80 mmHg based on the average of 2 to 3 readings, on at least 2 different occasions within the screening period.

  • Subjects who do not meet these criteria may be re-assessed after initiation or review of antihypertensive measures.
  • Subjects with a medical history of hypertension can be enrolled once they are medically clear (stable and compliant).
• Subject has a history of severe allergy, hypersensitivity or intolerance to drugs in general, including the study drug and any of its excipients.
• 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.
• Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyperplasia, endometrial cancer, or other clinically significant findings at screening.
• Subject has a history within the last 6 months of undiagnosed uterine bleeding.
• 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). Patients with mildly elevated ALT or AST up to 1.5 times the upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Patients with mildly elevated ALP (up to 1.5 x ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Patients with Gilbert's syndrome with elevated total bilirubin may be enrolled as long as direct bilirubin, hemoglobin and reticulocytes are normal.
• Subject has creatinine > 1.5 x 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.
• 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 [C-SSRS]), or who is at significant risk to commit suicide, as assessed at screening and at the time of visit 2 (randomization).
• Subject has previously been enrolled in a clinical trial with fezolinetant.
• Subject is participating concurrently in another interventional study or participated in an interventional study within 28 days prior to screening, or received any investigational drug within 28 days or within 5 half-lives prior to screening, whichever is longer.
• Subject is unable or unwilling to complete the study procedures.
• Subject has any condition which makes the subject unsuitable for study participation.
• Subject has had a partial or full hysterectomy.