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

Hot Flashes Clinical Trial

— Skylight 1  

Official title:

A Phase 3, Randomized, Placebo-controlled, 12-week Double-blind Study, Followed by a Non-Controlled Extension Treatment Period, to Assess the Efficacy and Safety of Fezolinetant in Women Suffering From Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated With Menopause

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04003155
• Other study ID #: 2693-CL-0301
• Secondary ID: 2018-003528-35
• Status: Completed
• Phase: Phase 3
• Start date: July 11, 2019
• Est. completion date: August 11, 2021

Study information

• Verified date: August 2023
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 527
• Est. completion date: August 11, 2021
• Est. primary completion date: October 29, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• fezolinetant
Oral Tablet
• placebo
Oral Tablet

Locations

Country	Name	City	State
Canada	Site CA15003	Brampton	Ontario
Canada	Site CA15002	Point Claire	Quebec
Canada	Site CA15001	Quebec
Canada	Site CA15004	Quebec
Canada	Site CA15006	Quebec City	Quebec
Czechia	Site CZ42001	Olomouc
Czechia	Site CZ42003	Vodnany	Jihocesky
Hungary	Site HU36004	Debrecen
Hungary	Site HU36001	Kecskemet
Hungary	Site HU36002	Szekesfeherver
Poland	Site PL48003	Bialystok
Poland	Site PL48004	Katowice
Poland	Site PL48012	Katowice	Slaskie
Poland	Site PL48013	Katowice
Poland	Site PL48007	Lublin
Poland	Site PL48005	Poznan
Poland	Site PL48014	Swidnik
Poland	Site PL48001	Warszawa
Poland	Site PL48009	Warszawa
Spain	Site ES34004	Sevilla
United Kingdom	Site GB44002	Coventry	Warwickshire
United Kingdom	Site GB44004	Middlesex
United Kingdom	Site GB44003	Orpington	Kent
United Kingdom	Site GB44001	Wokingham	Berkshire
United States	Accent Clinical Research Professionals	Allen	Texas
United States	SEC Clinical Research	Andalusia	Alabama
United States	Better Health Greater Life	Atlanta	Georgia
United States	Advanced Clinical Research - Rancho Paseo	Banning	California
United States	Central Research Associates	Birmingham	Alabama
United States	DiscoveResarch, Inc.	Bryan	Texas
United States	Gwinnett Research Institute	Buford	Georgia
United States	Alliance Research Inc	Canoga Park	California
United States	Hope Clinical Research, LLC	Canoga Park	California
United States	Velocity Clinical Research	Cincinnati	Ohio
United States	Complete Healthcare For Women	Columbus	Ohio
United States	IACT Health	Columbus	Georgia
United States	Precision Clinical Research	Coral Springs	Florida
United States	Avant Research Associates, LLC	Crowley	Louisiana
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	NuDirections Clinical Research	Duluth	Georgia
United States	Achieve Clinical Research, LLC	Ensley	Alabama
United States	Lillestol Research, LLC	Fargo	North Dakota
United States	Fleming Island Center for Clinical Research	Fleming Island	Florida
United States	Clinical Physiology Associates	Fort Myers	Florida
United States	Unified Women's Clinical Research	Greensboro	North Carolina
United States	Vital Pharma Research Inc.	Hialeah	Florida
United States	Marvel Clinical Research	Huntington Beach	California
United States	Protenium Clinical Research, LLC	Hurst	Texas
United States	The Healing Sanctuary, LLC	Idaho Falls	Idaho
United States	Health Awareness	Jupiter	Florida
United States	GYN Research Center	Kissimmee	Florida
United States	Grossmont Center for Clinical Research	La Mesa	California
United States	Centex Studies, Inc.	Lake Charles	Louisiana
United States	Multi-Specialty Research Associates, Inc.	Lake City	Florida
United States	Altus Research	Lake Worth	Florida
United States	Excel Clinical Research, LLC	Las Vegas	Nevada
United States	Office Of Edmond Pack, Md	Las Vegas	Nevada
United States	Ocean State Clinical Research Partners	Lincoln	Rhode Island
United States	National Research Institute - Panorama	Los Angeles	California
United States	Medical Research Center of Memphis LLC	Memphis	Tennessee
United States	Medical Research Center of Miami II	Miami	Florida
United States	New Age Medical Research Corporation	Miami	Florida
United States	Spotlight research center	Miami	Florida
United States	Montana Medical Research Inc	Missoula	Montana
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	International Clinical Research	Murfreesboro	Tennessee
United States	EPIC Medical Research	Murray	Utah
United States	Coastal Connecticut Research, LLC	New London	Connecticut
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Neuro-Behavioral Clinical Research, Inc	North Canton	Ohio
United States	Coastal Carolina Research Center	North Charleston	South Carolina
United States	Quality Clinical Research, Inc	Omaha	Nebraska
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	Philadelphia Clinical Research, LLC	Philadelphia	Pennsylvania
United States	Elite Clinical Studies, LLC	Phoenix	Arizona
United States	St. Johns Center for Clinical Research	Ponte Vedra	Florida
United States	Health Awareness	Port Saint Lucie	Florida
United States	Unified Womens Clinical Research	Raleigh	North Carolina
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	Infinite Clinical Trials	Riverdale	Georgia
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Northern California Research	Sacramento	California
United States	Saginaw Valley Medical Research Group, Llc	Saginaw	Michigan
United States	Precision Research Institute, Inc	San Diego	California
United States	International Clinical Research	Sanford	Florida
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Premier Medical Associates	The Villages	Florida
United States	Eclipse Clinical Research	Tucson	Arizona
United States	Tidewater Clinical Research, Inc.	Virginia Beach	Virginia
United States	Emerson Clinical Research Institute	Washington	District of Columbia
United States	Invocare Clinical Research Center	West Columbia	South Carolina
United States	Unified Women's Clinical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.	Baseline and week 4
Primary	Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.	Baseline and week 12
Primary	Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4	Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).; Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.	Baseline and week 4
Primary	Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12	Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).; Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.	Baseline and week 12
Secondary	Change From Baseline in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) Total Score at Week 12	The PROMIS SD SF 8b assesses self-reported sleep disturbance over the past 7 days and includes perceptions of restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Because it assesses the participants experience of sleep disturbance, the measure does not focus on specific sleep-disorder symptoms or ask patients to report objective measures of sleep (e.g., total amount of sleep, time to fall asleep and amount of wakefulness during sleep). Responses to each of the 8 items range from 1 (no disturbed sleep) to 5 (disturbed sleep), and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the disturbed sleep.	Baseline and week 12
Secondary	Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.	Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11
Secondary	Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12	Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).; Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.	Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11
Secondary	Mean Percent Change in The Frequency of Moderate And Severe VMS From Baseline to Each Study Week Up to Week 12	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.	Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Secondary	Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has >=50% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.	Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Secondary	Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has 100% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.	Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Secondary	Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit	The PGI is comprised of 2 companion 1-item PRO measures analogous to the Clinical Global Impression (CGI) scales. These measures provide brief, stand-alone global assessments prior to and after initiating a study medication. Patient-perceived change from the initiation of treatment (PGI-C)-VMS is used to evaluate meaningful within-person changes over time in VMS. This measure provides patient-perceived change from the initiation of treatment.; The PGI-C VMS asks: "Compared to the beginning of this study, how would you rate your HFs/night sweats now?" Subject ratings range from (1) much better to (7) much worse. Participant ratings range from 1=much better, 2= moderately better, 3= a little better, 4= no change, 5= a little worse, 6= moderately worse, 7= much worse.	Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 48, 52 of fezolinetant exposure (weeks 16, 24, 28, 32, 36, 40, 44, 48 and 52 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)
Secondary	Change From Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24	The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.	Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)
Secondary	Change From Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24	Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).; Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.	Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)
Secondary	Number of Participants With Adverse Events	An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with use of a medicinal product (mp) whether or not considered related to the mp. An AE is considered "serious" if it results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires inpatient hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. TEAE was defined as an AE observed from first dose date up to 21 days after last dose.	From first dose date up to 21 days after last dose (to 55 weeks)

External Links

•   Link to plain language summary of the study on the Trial Results Summaries website.
•   Link to results and other applicable study documents on the Astellas Clinical Trials website.