A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause (Skylight 1)

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

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.

Study Overview

• Status: Completed
• Conditions: Hot Flashes
• Intervention / Treatment: Drug: placebo; Drug: fezolinetant

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.

• Study Type: Interventional
• Enrollment (Actual): 527
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1N 4V3
    • Site CA15001
  • Quebec, Canada, G1W 4R4
    • Site CA15004
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Site CA15003
  • Quebec
    • Point Claire, Quebec, Canada, H9R 4S3
      • Site CA15002
    • Quebec City, Quebec, Canada, G3K 2P8
      • Site CA15006
• Czechia
  • Olomouc, Czechia, 772 00
    • Site CZ42001
  • Jihocesky
    • Vodnany, Jihocesky, Czechia, 389 01
      • Site CZ42003
• Hungary
  • Debrecen, Hungary, 4024
    • Site HU36004
  • Kecskemet, Hungary, 6000
    • Site HU36001
  • Szekesfeherver, Hungary, 8000
    • Site HU36002
• Poland
  • Bialystok, Poland, 15-224
    • Site PL48003
  • Katowice, Poland, 40-301
    • Site PL48013
  • Katowice, Poland, 40-611
    • Site PL48004
  • Lublin, Poland, 20362
    • Site PL48007
  • Poznan, Poland, 60-848
    • Site PL48005
  • Swidnik, Poland, 21040
    • Site PL48014
  • Warszawa, Poland, 02-679
    • Site PL48009
  • Warszawa, Poland, 02-798
    • Site PL48001
  • Slaskie
    • Katowice, Slaskie, Poland, 40-648
      • Site PL48012
• Spain
  • Sevilla, Spain, 41018
    • Site ES34004
• United Kingdom
  • Middlesex, United Kingdom, HA6 2RN
    • Site GB44004
  • Berkshire
    • Wokingham, Berkshire, United Kingdom, RG40 1XS
      • Site GB44001
  • Kent
    • Orpington, Kent, United Kingdom, BR5 3QG
      • Site GB44003
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV3 4FJ
      • Site GB44002
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • SEC Clinical Research
    • Birmingham, Alabama, United States, 59405
      • Central Research Associates
    • Ensley, Alabama, United States, 35218
      • Achieve Clinical Research, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies, LLC
    • Tucson, Arizona, United States, 85745
      • Eclipse Clinical Research
  • California
    • Banning, California, United States, 92220
      • Advanced Clinical Research - Rancho Paseo
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, LLC
    • Canoga Park, California, United States, 91304
      • Alliance Research Inc
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • La Mesa, California, United States, 91942
      • Grossmont Center for Clinical Research
    • Los Angeles, California, United States, 90057
      • National Research Institute - Panorama
    • Sacramento, California, United States, 95821
      • Northern California Research
    • San Diego, California, United States, 92114
      • Precision Research Institute, Inc
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20011
      • Emerson Clinical Research Institute
  • Florida
    • Coral Springs, Florida, United States, 33065
      • Precision Clinical Research
    • Cutler Bay, Florida, United States, 33157
      • American Research Institute, Inc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Doral, Florida, United States, 33166
      • Universal Axon Clinical Research
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Fort Myers, Florida, United States, 33912
      • Clinical Physiology Associates
    • Hialeah, Florida, United States, 33016
      • Vital Pharma Research Inc.
    • Jupiter, Florida, United States, 33458
      • Health Awareness
    • Kissimmee, Florida, United States, 34741
      • GYN Research Center
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • Miami, Florida, United States, 33186
      • New Age Medical Research Corporation
    • Miami, Florida, United States, 33134
      • Medical Research Center of Miami II
    • Miami, Florida, United States, 33176
      • Spotlight research center
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc
    • Orlando, Florida, United States, 32822
      • Cornerstone Research Institute
    • Ponte Vedra, Florida, United States, 32081
      • St. Johns Center for Clinical Research
    • Port Saint Lucie, Florida, United States, 34952
      • Health Awareness
    • Sanford, Florida, United States, 32771
      • International Clinical Research
    • The Villages, Florida, United States, 32159
      • Premier Medical Associates
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Better Health Greater Life
    • Buford, Georgia, United States, 30519
      • Gwinnett Research Institute
    • Columbus, Georgia, United States, 31904
      • IACT Health
    • Duluth, Georgia, United States, 30096
      • NuDirections Clinical Research
    • Riverdale, Georgia, United States, 30274
      • Infinite Clinical Trials
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • The Healing Sanctuary, LLC
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Avant Research Associates, LLC
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc.
  • Michigan
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Medical Research Group, LLC
  • Montana
    • Missoula, Montana, United States, 59801
      • Montana Medical Research Inc
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research, LLC
    • Las Vegas, Nevada, United States, 89113
      • Office of Edmond Pack, MD
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27607
      • Unified Womens Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Unified Women's Clinical Research
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research
    • Columbus, Ohio, United States, 43231
      • Complete Healthcare For Women
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research, Inc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Philadelphia Clinical Research, LLC
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Ocean State Clinical Research Partners
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
    • North Charleston, South Carolina, United States, 29406
      • Coastal Carolina Research Center
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
    • West Columbia, South Carolina, United States, 29169
      • Invocare Clinical Research Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Medical Research Center of Memphis LLC
    • Murfreesboro, Tennessee, United States, 37130
      • International Clinical Research
  • Texas
    • Allen, Texas, United States, 75013
      • Accent Clinical Research Professionals
    • Bryan, Texas, United States, 77802
      • DiscoveResarch, Inc.
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research, LLC
  • Utah
    • Murray, Utah, United States, 84123
      • Epic Medical Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Tidewater Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: placebo; Oral Tablet
Experimental: 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.	Drug: fezolinetant; Oral Tablet
Experimental: 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.	Drug: fezolinetant; Oral Tablet
Experimental: 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.	Drug: fezolinetant; Oral Tablet
Experimental: 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.	Drug: fezolinetant; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Executive Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Actual): October 29, 2020
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: vasomotor symptoms; menopause; ESN364; fezolinetant
• Additional Relevant MeSH Terms: Hot Flashes
• Other Study ID Numbers: 2693-CL-0301; 2018-003528-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No