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

NCT04451226 | Completed Phase 3 DMC

• 2 other identifiers: 2693-CL-0307CTR20200676
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 29

Brief 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 treatment is fezolinetant (1 tablet of fezolinetant) once a day. The study participants will take study treatment for 52 weeks. 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. 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.

Conditions

Hot Flashes

Keywords

Vasomotor Symptoms; menopause; fezolinetant; ESN364

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  An adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.

  Up to 55 weeks

• Number of Participants With Adverse Events Based on Severity

  An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.

  Up to 55 weeks

Secondary Outcomes (13)

• Change From Baseline in Endometrial Thickness

  Baseline and 52 weeks

• Percentage of Participants With Endometrial Hyperplasia and/or Endometrial Cancer

  Up to 52 weeks

• Number of Participants With Vital Sign Abnormalities and/or Adverse Events (AEs)

  Up to 55 weeks

• Number of Participants With Laboratory Value Abnormalities and/or Adverse Events (AEs)

  Up to 55 weeks

• Number of Participants With Suicidal Ideation and/or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

  Up to 55 weeks

Study Arms (1)

Fezolinetant

EXPERIMENTAL

Participants will receive fezolinetant 30 milligrams (mg) orally once daily for 52 weeks.

Drug: Fezolinetant

Interventions

Fezolinetant DRUG

Oral

Also known as: ESN364, VEOZAH

Fezolinetant

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma China, Inc.: lead

Study Sites (29)

Site CN86002

Beijing, China

Location

Site CN86015

Beijing, China

Location

Site CN86029

Beijing, China

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Site CN86032

Chengdu, China

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Site CN86001

Guangzhou, China

Location

Site CN86019

Guangzhou, China

Location

Site CN86022

Guangzhou, China

Location

Site CN86040

Guangzhou, China

Location

Site CN86042

Guangzhou, China

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Site CN86008

Hangzhou, China

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Site CN86012

Hangzhou, China

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Site CN86005

Hunan, China

Location

Site CN86039

Jiangsu, China

Location

Site CN86010

Jinlin, China

Location

Site CN86020

Kunming, China

Location

Site CN86037

Liuchow, China

Location

Site CN86006

Nanjing, China

Location

Site CN86007

Nanjing, China

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Site CN86018

Nanning, China

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Site CN86034

Ningxia Hui Nationality Autonomous Region, China

Location

Site CN86009

Shanghai, China

Location

Site CN86011

Shanxi, China

Location

Site CN86004

Shenzhen, China

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Site CN86028

Shijiazhuang, China

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Site CN86026

Suzhou, China

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Site CN86038

Taiyuan, China

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Site CN86030

Tianjin, China

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Site CN86036

Tianjin, China

Location

Site CN86025

Wuhan, China

Location

Related Publications (1)

• Yu Q, Ming F, Ma J, Cai Y, Wang L, Ren M, Zhang J, Ma X, Miyazaki K, He W, Wang X. Long-term safety of fezolinetant in Chinese women with vasomotor symptoms associated with menopause: the phase 3 open-label MOONLIGHT 3 clinical trial. J Int Med Res. 2024 May;52(5):3000605241246624. doi: 10.1177/03000605241246624.

  PMID: 38818887 DERIVED

Related Links

• Link Description: Link to plain language summary of the study on the Trial Results Summaries website.

MeSH Terms

Conditions

Hot Flashes

Interventions

fezolinetant

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Astellas Pharma China, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: June 30, 2020
• Study Start: July 30, 2020
• Primary Completion: June 13, 2022
• Study Completion: June 13, 2022
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

CN (29)