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

• Status: Active, not recruiting
• Trial end date: 2022-01-31
• Target enrollment: 0
• Participant gender: Female

Summary

This study is for women in menopause with hot flashes. Menopause, a normal part of aging, is the time of a woman's last period. Hot flashes can interrupt a woman's daily life.

The purpose of this study is to find out how safe it is for these women to take fezolinetant long term (up to 52 weeks). To do that, the study will look at the number and severity of the "adverse events." Those are the side effects that study participants have while they are in the study.

The study treatments are fezolinetant low dose (1 tablet of fezolinetant and 1 placebo tablet) once a day, fezolinetant high dose (2 tablets of fezolinetant) once a day or placebo (2 tablets) once a day. (Placebo is a dummy treatment that looks like medicine but does not have any medicine in it.) Women in this study will be picked for 1 of the 3 study treatments by chance alone. The study participants will take study treatment for 52 weeks.

This study is "double-blinded." That means that the study participants and the study doctors do not know who takes which of the study treatments (fezolinetant low dose, fezolinetant high dose or placebo).

At weeks 2 and 4 and then once a month, the study participants will go the hospital or clinic for a check-up. They will be asked about medications, side effects and how they feel. Other checks will include physical exam and vital signs (heart rate, temperature and blood pressure). Blood and urine will be collected for laboratory tests. At some study visits, study participants will complete questionnaires that are about their quality of life. At the first and last study visits, they will have a dual-energy x-ray absorptiometry (DXA for short) test done. To measure bone loss in the hips and spine, DXA creates pictures of the inside of these areas with low-dose x-rays. (The dose is approximately one-tenth of the amount of a normal chest x-ray.) Study participants who still have their uterus will have 2 more tests done at the first and last study visits. One of the 2 tests is endometrial biopsy. This test involves removing a small amount of tissue from the inside lining of the uterus. The tissue is then checked under a microscope. The other test is transvaginal ultrasound. It uses sound waves to create pictures of the organs in the pelvis. The sound waves are transmitted by a probe (transducer), which is placed inside the vagina. Study participants may have a screening mammogram done at the first and/or last study visit. A mammogram is an x-ray picture of the breasts used to screen for breast cancer. Study participants who did not have this test done in the last 12 months will have it done at the first study visit. They will have it done at the last study visit if they are due for their screening mammogram and their own doctor agrees.

The last check-up at the hospital or clinic will be 3 weeks after the last dose of study treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Astellas Pharma Global Development, Inc.

Criteria

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.