A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause

NCT ID: NCT04003155

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 527 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-11
• Study Completion Date: 2021-08-11

Brief Summary

This study was for women in menopause with moderate to severe 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 study treatments were fezolinetant 30 milligrams (mg) (1 tablet of fezolinetant and 1 placebo tablet) once a day, fezolinetant 45 mg (2 tablets of fezolinetant) once a day or placebo (2 tablets) once a day. (Placebo was a dummy treatment that looks like medicine but did not had any medicine in it.) The study compared fezolinetant and placebo after 4 and 12 weeks of dosing. The study evaluated if fezolinetant reduces the number of hot flashes. And the study evaluated if fezolinetant reduces the severity of the hot flashes. Women in the study received an electronic handheld device at the first study visit. (It was similar to a smart phone.) Each day of the study, study participants used this to record their hot flashes. Their record for the 10 days before the start of study treatment was checked. They remained in the study if their record shown 7 or 8 moderate to severe hot flashes per day (50 or more per week). Next, they were picked for 1 of the 2 study treatments (fezolinetant or placebo) by chance alone. It was like flipping a coin. The study participants took study treatment for 52 weeks. The first 12 weeks of study treatment are "double-blinded." That means that the study participants and the study doctors did not knew who took which of the study treatments (fezolinetant 30 mg, fezolinetant 45 mg or placebo) during that time. The last 40 weeks of study treatment are "noncontrolled." That means that each study participant and the study doctors knew which study treatment that study participant took during that time. Women who took fezolinetant during the first 12 weeks continued to take the same dose. Women who took placebo during the first 12 weeks took fezolinetant. Their dose was either 30 mg or 45 mg fezolinetant. At weeks 2, 4, 8, 12, 14, 16 and then once a month, the study participants visited the hospital or clinic for a check-up. They were asked about medications, side effects and how they felt. Other checks included physical exam and vital signs (heart rate, temperature and blood pressure). Blood and urine was collected for laboratory tests. Study participants completed questionnaires that were about how hot flashes affect their daily life. Study participants who still had their uterus had the following 2 tests done at the first and last study visits. One of the 2 tests was endometrial biopsy. This test involves removing a small amount of tissue from the inside lining of the uterus. The tissue was then checked under a microscope. The other test is transvaginal ultrasound. This test used sound waves to create pictures of the organs in the pelvis. The sound waves were transmitted by a probe (transducer), which was 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 had this test done in the last 12 months had it done at the first study visit. They had 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 was 3 weeks after the last dose of study treatment.

Detailed Description

This study consisted of a screening period and a 52 week treatment period. Safety follow up occurred 3 weeks after the last dose of study drug.

Conditions

Hot Flashes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Double-blind Period: Placebo

Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Oral Tablet

Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg

Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.

Group Type: EXPERIMENTAL

fezolinetant

Intervention Type: DRUG

Oral Tablet

Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg

Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.

Group Type: EXPERIMENTAL

fezolinetant

Intervention Type: DRUG

Oral Tablet

Double-blind Period: Placebo /Extension Period: Fezolinetant 30 mg

Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.

Group Type: EXPERIMENTAL

fezolinetant

Intervention Type: DRUG

Oral Tablet

Double-blind Period: Placebo /Extension Period: Fezolinetant 45 mg

Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.

Group Type: EXPERIMENTAL

fezolinetant

Intervention Type: DRUG

Oral Tablet

Interventions

fezolinetant

Oral Tablet

Intervention Type: DRUG

placebo

Oral Tablet

Intervention Type: DRUG

Eligibility 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 [FSH] > 40 IU/L); or
• Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
• Within the 10 days prior to randomization, subject must have a minimum average of 7 to 8 moderate to severe hot flashes (HFs) vasomotor symptoms (VMS) per day, or 50 to 60 per week.
• 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 electrocardiogram (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 findings mammogram (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), and for subjects who are withdrawn from the study prior to completion, a TVU at the early discontinuation (ED) visit.
• Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT), for subjects with uterine bleeding, and for subjects who are withdrawn from the study prior to completion. 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 1A2 [CYP1A2] inhibitors, hormone replacement therapy [HRT], hormonal contraceptive or any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue use of such drugs for the full duration of study conduct.
• Subject has 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 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 × ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula ≤ 59 mL/min per 1.73 m^2 at screening.
• 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 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 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 partial or full hysterectomy.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

SEC Clinical Research

Andalusia, Alabama, United States

Central Research Associates

Birmingham, Alabama, United States

Achieve Clinical Research, LLC

Ensley, Alabama, United States

Elite Clinical Studies, LLC

Phoenix, Arizona, United States

Eclipse Clinical Research

Tucson, Arizona, United States

Advanced Clinical Research - Rancho Paseo

Banning, California, United States

Hope Clinical Research, LLC

Canoga Park, California, United States

Alliance Research Inc

Canoga Park, California, United States

Marvel Clinical Research

Huntington Beach, California, United States

Grossmont Center for Clinical Research

La Mesa, California, United States

National Research Institute - Panorama

Los Angeles, California, United States

Northern California Research

Sacramento, California, United States

Precision Research Institute, Inc

San Diego, California, United States

Coastal Connecticut Research, LLC

New London, Connecticut, United States

Emerson Clinical Research Institute

Washington D.C., District of Columbia, United States

Precision Clinical Research

Coral Springs, Florida, United States

American Research Institute, Inc.

Cutler Bay, Florida, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Universal Axon Clinical Research

Doral, Florida, United States

Fleming Island Center for Clinical Research

Fleming Island, Florida, United States

Clinical Physiology Associates

Fort Myers, Florida, United States

Vital Pharma Research Inc.

Hialeah, Florida, United States

Health Awareness

Jupiter, Florida, United States

GYN Research Center

Kissimmee, Florida, United States

Multi-Specialty Research Associates, Inc.

Lake City, Florida, United States

Altus Research

Lake Worth, Florida, United States

Medical Research Center of Miami II

Miami, Florida, United States

Spotlight research center

Miami, Florida, United States

New Age Medical Research Corporation

Miami, Florida, United States

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States

Clinical Neuroscience Solutions, Inc

Orlando, Florida, United States

Clinical Neuroscience Solutions, Inc

Orlando, Florida, United States

Cornerstone Research Institute

Orlando, Florida, United States

St. Johns Center for Clinical Research

Ponte Vedra, Florida, United States

Health Awareness

Port Saint Lucie, Florida, United States

International Clinical Research

Sanford, Florida, United States

Premier Medical Associates

The Villages, Florida, United States

Better Health Greater Life

Atlanta, Georgia, United States

Gwinnett Research Institute

Buford, Georgia, United States

IACT Health

Columbus, Georgia, United States

NuDirections Clinical Research

Duluth, Georgia, United States

Infinite Clinical Trials

Riverdale, Georgia, United States

The Healing Sanctuary, LLC

Idaho Falls, Idaho, United States

Avant Research Associates, LLC

Crowley, Louisiana, United States

Centex Studies, Inc.

Lake Charles, Louisiana, United States

Saginaw Valley Medical Research Group, Llc

Saginaw, Michigan, United States

Montana Medical Research Inc

Missoula, Montana, United States

Quality Clinical Research, Inc

Omaha, Nebraska, United States

Excel Clinical Research, LLC

Las Vegas, Nevada, United States

Office Of Edmond Pack, Md

Las Vegas, Nevada, United States

Rochester Clinical Research, Inc.

Rochester, New York, United States

Unified Women's Clinical Research

Greensboro, North Carolina, United States

Unified Womens Clinical Research

Raleigh, North Carolina, United States

Wake Research Associates, LLC

Raleigh, North Carolina, United States

Unified Women's Clinical Research

Winston-Salem, North Carolina, United States

Lillestol Research, LLC

Fargo, North Dakota, United States

Velocity Clinical Research

Cincinnati, Ohio, United States

Complete Healthcare For Women

Columbus, Ohio, United States

Neuro-Behavioral Clinical Research, Inc

North Canton, Ohio, United States

Philadelphia Clinical Research, LLC

Philadelphia, Pennsylvania, United States

Ocean State Clinical Research Partners

Lincoln, Rhode Island, United States

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, United States

Coastal Carolina Research Center

North Charleston, South Carolina, United States

Palmetto Clinical Research

Summerville, South Carolina, United States

Invocare Clinical Research Center

West Columbia, South Carolina, United States

Medical Research Center of Memphis LLC

Memphis, Tennessee, United States

International Clinical Research

Murfreesboro, Tennessee, United States

Accent Clinical Research Professionals

Allen, Texas, United States

DiscoveResarch, Inc.

Bryan, Texas, United States

Protenium Clinical Research, LLC

Hurst, Texas, United States

EPIC Medical Research

Murray, Utah, United States

Tidewater Clinical Research, Inc.

Virginia Beach, Virginia, United States

Site CA15003

Brampton, Ontario, Canada

Site CA15002

Point Claire, Quebec, Canada

Site CA15001

Québec, Quebec, Canada

Site CA15004

Québec, Quebec, Canada

Site CA15006

Québec, Quebec, Canada

Site CZ42003

Vodňany, Jihočeský kraj, Czechia

Site CZ42001

Olomouc, , Czechia

Site HU36004

Debrecen, , Hungary

Site HU36001

Kecskemét, , Hungary

Site HU36002

Szekesfeherver, , Hungary

Site PL48012

Katowice, Silesian Voivodeship, Poland

Site PL48003

Bialystok, , Poland

Site PL48013

Katowice, , Poland

Site PL48004

Katowice, , Poland

Site PL48007

Lublin, , Poland

Site PL48005

Poznan, , Poland

Site PL48014

Świdnik, , Poland

Site PL48009

Warsaw, , Poland

Site PL48001

Warsaw, , Poland

Site ES34004

Seville, , Spain

Site GB44001

Wokingham, Berkshire, United Kingdom

Site GB44003

Orpington, Kent, United Kingdom

Site GB44002

Coventry, Warwickshire, United Kingdom

Site GB44004

Middlesex, , United Kingdom

Countries

United States; Canada; Czechia; Hungary; Poland; Spain; United Kingdom

References

Santoro N, Neal-Perry G, Stute P, Blogg M, Mancuso S, Morga A, Ottery FD, Siddiqui E. Fezolinetant effect on vasomotor symptoms due to menopause in women unsuitable for hormone therapy. Curr Med Res Opin. 2025 Feb;41(2):375-384. doi: 10.1080/03007995.2025.2470752. Epub 2025 Mar 5.

Reference Type: DERIVED

PMID: 40044127 (View on PubMed)

Kagan R, Cano A, Nappi RE, English ML, Mancuso S, Wu X, Ottery FD. Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies. Adv Ther. 2025 Feb;42(2):1147-1164. doi: 10.1007/s12325-024-03073-8. Epub 2024 Dec 30.

Reference Type: DERIVED

PMID: 39739195 (View on PubMed)

Morga A, Zimmermann L, Valluri U, Siddiqui E, McLeod L, Bender RH. Validation and Application of Thresholds to Define Meaningful Change in Vasomotor Symptoms Frequency: Analysis of Pooled SKYLIGHT 1 and 2 Data. Adv Ther. 2024 Jul;41(7):2845-2858. doi: 10.1007/s12325-024-02849-2. Epub 2024 May 22.

Reference Type: DERIVED

PMID: 38775925 (View on PubMed)

Schultz NM, Morga A, Siddiqui E, Rhoten SE. Psychometric Evaluation of the MENQOL Instrument in Women Experiencing Vasomotor Symptoms Associated with Menopause. Adv Ther. 2024 Jun;41(6):2233-2252. doi: 10.1007/s12325-024-02787-z. Epub 2024 Feb 24.

Reference Type: DERIVED

PMID: 38396203 (View on PubMed)

Schultz NM, Morga A, Siddiqui E, Rhoten SE. Psychometric evaluation of the PROMIS SD-SF-8b instrument in individuals experiencing vasomotor symptoms due to menopause. Health Qual Life Outcomes. 2023 Nov 21;21(1):126. doi: 10.1186/s12955-023-02206-x.

Reference Type: DERIVED

PMID: 37990323 (View on PubMed)

O'Malley PA. A Nonhormonal Selective NK3R Antagonist for Moderate to Severe Vasomotor Symptoms in Menopause. Clin Nurse Spec. 2023 Nov-Dec 01;37(6):259-261. doi: 10.1097/NUR.0000000000000774. No abstract available.

Reference Type: DERIVED

PMID: 37870510 (View on PubMed)

Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, English M, Franklin C, Lee M, Neal-Perry G. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102. doi: 10.1016/S0140-6736(23)00085-5. Epub 2023 Mar 13.

Reference Type: DERIVED

PMID: 36924778 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=14542&tenant=MT_AST_9011

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

Other Identifiers

2018-003528-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2693-CL-0301

Identifier Type: -

Identifier Source: org_study_id