A Study to Find the Best Dose of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause

NCT05034042 | Completed Phase 2 DMC

• 2 other identifiers: 2693-CL-0206jRCT2031210334
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 40

Brief Summary

This study is for menopausal women who have hot flashes. Menopause, a normal part of life, is the time after a woman's last period. Hot flashes often occur during menopause. They can disrupt a woman's daily life. This study will take place in Japan. This study will provide more information on a potential new treatment, called fezolinetant. The treatments in this study are fezolinetant or a placebo. In this study, a placebo is a dummy treatment that looks like fezolinetant but does not have any medicine in it. The study will compare fezolinetant with the placebo to find the best dose of fezolinetant to reduce the number and severity of hot flashes. Women that want to take part in the study will be given an electronic handheld device to track their hot flashes. In the last 10 days before their next clinic visit, the women will record information about their hot flashes. Women will be picked for 1 of 3 treatments (lower or higher dose of fezolinetant, or placebo) by chance alone. Women who take part in the study will take 2 tablets every day for 12 weeks. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study medicines (lower or higher dose of fezolinetant, or placebo). The women will continue recording information about their hot flashes on the electronic device. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic several times for a check-up. This will happen during weeks 2, 4, 8, 12 and 15. At the check-up, they will be asked if they have any medical problems. Other checks will include some blood samples taken for laboratory tests. At some check-ups, the women will have a physical exam, an ECG to check their heart rhythm, and their vital signs checked (pulse rate, temperature and blood pressure). At the first visit and in week 15, women who have a uterus will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs. The last check-up (at week 15) will be 3 weeks after they take their last tablets of study medicine (lower or higher dose of fezolinetant or placebo).

Conditions

Hot Flashes

Keywords

Vasomotor Symptoms (Hot Flashes) Associated with Menopause; ESN364; fezolinetant

Outcome Measures

Primary Outcomes (1)

• Mean change from baseline in the frequency of mild, moderate and severe vasomotor symptom (VMS)

  Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day.

  Baseline and Week 8

Secondary Outcomes (7)

• Mean change from baseline in the frequency of mild, moderate and severe VMS

  Baseline and up to Week 12

• Number of participants with Adverse Events (AEs)

  Up to Week 15

• Change from baseline in endometrial thickness

  Baseline and Week 12

• Number of participants with laboratory value abnormalities and/or AEs

  Up to Week 15

• Number of participants with vital sign abnormalities and/or AEs

  Up to Week 15

Study Arms (3)

Fezolinetant: low dose (15 mg)

EXPERIMENTAL

Participants will receive low dose of fezolinetant once daily for 12 weeks.

Drug: Fezolinetant

Fezolinetant: high dose (30 mg)

EXPERIMENTAL

Participants will receive high dose of fezolinetant once daily for 12 weeks.

Drug: Fezolinetant

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo once daily for 12 weeks.

Drug: Placebo

Interventions

Fezolinetant DRUG

oral

Also known as: ESN364

Fezolinetant: high dose (30 mg); Fezolinetant: low dose (15 mg)

Placebo DRUG

oral

Placebo

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 screening visit.
• 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:
• For post-menopausal subjects:
• Spontaneous amenorrhea for ≥ 12 consecutive months
• Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (follicle-stimulating hormone \[FSH\] \> 40 IU/L); or
• Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit (with or without hysterectomy)
• For peri-menopausal subjects:
• Skipped menstrual period with amenorrhea for ≥ 60 days but \< 6 consecutive months with biochemical criteria of peri-menopause (FSH \> 25 IU/L); or
• Spontaneous amenorrhea for ≥ 6 months but \< 12 consecutive months with biochemical criteria of peri-menopause (FSH \> 25 IU/L and ≤ 40 IU/L)
• Within the 10 days prior to randomization, subject must have a minimum average of 7 mild, moderate and severe hot flashes (VMS) per day.
• Subject is not pregnant and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 21 days after the final study treatment administration
• Subject must agree not to breastfeed starting at screening and throughout the study period and for 21 days after the final study treatment administration.
• Subject must not donate ova starting at first dose of investigational product (IP) and throughout the study period and for 21 days after the final study treatment administration.

You may not qualify if:

• Subject uses a prohibited therapy (strong or moderate cytochrome P450 1A2 \[CYP1A2\] inhibitors, hormone replacement therapy \[HRT\], hormonal contraceptive or any treatment for VMS \[prescription, over the counter, or herbal/Chinese medicine\]) or is not willing to wash out and discontinue use of such drugs for the full duration of study conduct or it is not medically appropriate to discontinue such drugs for the duration of the study.
• Subject has 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.
• Subject has a history of severe allergy, hypersensitivity, or intolerance to drugs in general, including the IP 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).
• Subject has a history of an undiagnosed uterine bleeding within the previous 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 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 mL/min/1.73 m\^2 at screening visit.
• Subject has a previous positive test for the human immunodeficiency virus.
• 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 question 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 at screening and at visit 2.
• Subject has had previous exposure with fezolinetant.
• Subject has received an IP within 28 days or 5 half-lives, whichever is longer, prior to screening.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (40)

Juno Vesta Clinic Hatta

Matsudo-shi, Chiba, Japan

Location

Mori Ladies Clinic

Fukuoka, Fukuoka, Japan

Location

SANO Women's Clinic

Fukuoka, Fukuoka, Japan

Location

Japan Organization of Occupational Health and Safety Kyushu Rosai Hospital

Kitakyusyu-shi, Fukuoka, Japan

Location

Ena Odori Clinic

Sapporo, Hokkaido, Japan

Location

Kotoni Ladies Clinic

Sapporo, Hokkaido, Japan

Location

M's Ladies Clinic

Sapporo, Hokkaido, Japan

Location

Nishikawa Women's Health Clinic

Sapporo, Hokkaido, Japan

Location

Sapporo Medical Center, NTT East Corporation

Sapporo, Hokkaido, Japan

Location

Tonan Hospital

Sapporo, Hokkaido, Japan

Location

Asahi-Clinic

Takamatsu, Kagawa-ken, Japan

Location

Unoki Clinic

Kagoshima, Kagoshima-ken, Japan

Location

Yoshinaga Women's Clinic

Kagoshima, Kagoshima-ken, Japan

Location

Sophia Ladies Clinic

Sagamihara-shi, Kanagawa, Japan

Location

Tawada Ladies Clinic

Yokohama, Kanagawa, Japan

Location

Women's Clinic LUNA Yokohama Motomachi

Yokohama, Kanagawa, Japan

Location

Kyoto City Hospital

Kyoto, Kyoto, Japan

Location

Chieko Yukika Lady's Clinic

Sendai, Miyagi, Japan

Location

Social Medical Care Corporation Hosei-kai Marunouchi Hospital

Matsumoto-shi, Nagano, Japan

Location

Kurashiki Medical Clinic

Kurashiki-shi, Okayama-ken, Japan

Location

GyNet Medical Corporation Minamimorimachi Ladies' Clinic

Osaka, Osaka, Japan

Location

Nomura Clinic Namba

Osaka, Osaka, Japan

Location

jMOG Medical Corporation Tanabe Ladies' Clinic

Takatsuki-shi, Osaka, Japan

Location

Maruyama Memorial General Hospital

Saitama-shi, Saitama, Japan

Location

Omi Medical Center, Social Medical Corporation Seikoukai

Kusatsu-shi, Shiga, Japan

Location

Omihachiman Community Medical Center

Ōmihachiman, Shiga, Japan

Location

Hamada Hospital

Chiyoda-ku, Tokyo, Japan

Location

Ginza Yoshida Clinic

Chuo-Ku, Tokyo, Japan

Location

Medical Corporation Asbo Tokyo Asbo Clinic

Chuo-ku, Tokyo, Japan

Location

Medical Corp. SEIKOUKAI New Medical Research System Clinic

Hachioji-shi, Tokyo, Japan

Location

Toranomon Womens Clinic

Minato-ku, Tokyo, Japan

Location

Yokokura Clinic

Minato-ku, Tokyo, Japan

Location

Shimamura Memorial Hospital

Nerima-ku, Tokyo, Japan

Location

Yukawa Women's Clinic

Nishi-Tokyo-shi, Tokyo, Japan

Location

Seijo Kinoshita Hospital

Setagaya-ku, Tokyo, Japan

Location

Ikebukuro Clinic

Toshima-ku, Tokyo, Japan

Location

Ikebukuro Metropolitan Clinic

Toshima-ku, Tokyo, Japan

Location

Kurobe City Hospital

Kurobe-shi, Toyama, Japan

Location

Japan Organization of Occupational Health and Safety Toyama Rosai Hospital

Uozu-shi, Toyama, Japan

Location

Japan Community Healthcare Organization Tokuyama Central Hospital

Shunan-shi, Yamaguchi, Japan

Location

Related Links

• 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 Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 5, 2021
• Study Start: November 17, 2021
• Primary Completion: November 11, 2022
• Study Completion: December 23, 2022
• Last Updated: October 26, 2024

Record last verified: 2024-10

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

JP (40)