A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause (Skylight 4)

A Randomized, Placebo-Controlled, Double-Blind Phase 3 Clinical Study to Investigate the Long-Term Safety of Fezolinetant in Women Suffering From Vasomotor Symptoms (Hot Flashes) Associated With Menopause

This study was for women in menopause with hot flashes. Menopause, a normal part of aging, was the time of a woman's last period. Hot flashes can interrupt a woman's daily life.

The purpose of this study was to find out how safe it is for these women to take fezolinetant in long term (up to 52 weeks). To do that, the study looked at the number and severity of the "adverse events." Those were the side effects that study participants had while they were in the study.

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 looked like medicine but did not have any medicine in it.) Women in this study were picked for 1 of the 3 study treatments by chance alone. The study participants took study treatment for 52 weeks.

This study was "double-blinded." That means that the study participants and the study doctors did not know who took which of the study treatments (fezolinetant 30 mg, fezolinetant 45 mg or placebo).

At weeks 2 and 4 and then once a month, the study participants went to 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 were collected for laboratory tests. At some study visits, study participants completed questionnaires that were about their quality of life. At the first and last study visits, they had a dual-energy x-ray absorptiometry (DXA for short) test done. To measure bone loss in the hips and spine, DXA created pictures of the inside of these areas with low-dose x-rays. (The dose was approximately one-tenth of the amount of a normal chest x-ray.) Study participants who still had their uterus had 2 more tests done at the first and last study visits. One of the 2 tests was endometrial biopsy. This test involved removing a small amount of tissue from the inside lining of the uterus. The tissue was then checked under a microscope. The other test was transvaginal ultrasound. It 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 might have had 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 done at the last study visit if they were due for their screening mammogram and their own doctor agreed.

The last check-up at the hospital or clinic was at 3 weeks after the last dose of study treatment.

Study Overview

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

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): 1831
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1N 4V3
    • Site CA15002
  • Quebec, Canada, G1W 4R4
    • Site CA15009
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Site CA15005
    • Burlington, Ontario, Canada, L7M 4Y1
      • Site CA15006
    • Sarnia, Ontario, Canada, N7T 4X3
      • Site CA15010
    • Toronto, Ontario, Canada, M9W 4L6
      • Site CA15007
  • Quebec
    • Levis, Quebec, Canada
      • Site CA15012
    • Point Claire, Quebec, Canada, H9R 4S3
      • Site CA15004
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Site CA15003
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Site CA15001
• Czechia
  • Olomouc, Czechia, 772 00
    • Site CZ42001
  • Olomouc, Czechia, 779 00
    • Site CZ42003
  • Pisek, Czechia, 39701
    • Site CZ42010
  • Praha 2, Czechia, 12000
    • Site CZ42009
  • Tabor 3, Czechia, 39003
    • Site CZ42005
  • Jihocesky
    • Vodnany, Jihocesky, Czechia, 389 01
      • Site CZ42008
• Latvia
  • Riga, Latvia, 1005
    • Site LV37102
  • Riga, Latvia, 1010
    • Site LV37101
• Poland
  • Bialystok, Poland, 15-224
    • Site PL48004
  • Bydgoszcz, Poland, 85-065
    • Site PL48005
  • Katowice, Poland, 40-611
    • Site PL48002
  • Katowice, Poland, 40-851
    • Site PL48019
  • Lublin, Poland, 20-069
    • Site PL48006
  • Lublin, Poland, 20362
    • Site PL48014
  • Poznan, Poland, 60-192
    • Site PL48016
  • Szczecin, Poland, 71-434
    • Site PL48010
  • Warsaw, Poland, 02-201
    • Site PL48020
  • Warszawa, Poland, 02-798
    • Site PL48003
  • Warszawa, Poland, 02777
    • Site PL48007
• Spain
  • Centelles, Spain, 08540
    • Site ES34005
  • Madrid, Spain, 28041
    • Site ES34002
• Ukraine
  • Kiev, Ukraine
    • Site UA38006
  • Zaporizka Oblast
    • Zaporizhzhya, Zaporizka Oblast, Ukraine, 69065
      • Site UA38004
• United Kingdom
  • Middlesex, United Kingdom, HA6 2RN
    • Site GB44006
  • Romford, United Kingdom
    • Site GB44007
  • Shipley, United Kingdom, BD18 3SA
    • Site GB44001
  • Berkshire
    • Wokingham, Berkshire, United Kingdom, RG40 1XS
      • Site GB44003
  • Kent
    • Sidcup, Kent, United Kingdom, DA146LT
      • Site GB44008
  • Northamptonshire
    • Corby, Northamptonshire, United Kingdom, NN17 2UR
      • Site GB44005
  • Warwickshire
    • Kenilworth, Warwickshire, United Kingdom, CV8 1JD
      • Site GB44004
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • SEC Clinical Research
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, LLC
    • Birmingham, Alabama, United States, 35205
      • Alabama Clinical Therapeutics, LLC
    • Ensley, Alabama, United States, 35218
      • Achieve Clinical Research, LLC
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Mesa Obstetricians and Gynecologists
    • Phoenix, Arizona, United States, 85032
      • Precision Trials
    • Phoenix, Arizona, United States, 85015
      • MedPharmics LLC
    • Tucson, Arizona, United States, 85712
      • Del Sol Research Management
    • Tucson, Arizona, United States, 85745
      • Eclipse Clinical Research
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research - Tuscon
  • California
    • Canoga Park, California, United States, 91304
      • Alliance Research Inc
    • Canoga Park, California, United States, 91303
      • HOPE Research Institute
    • 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, 90017
      • Downtown L.A. Research Center, Inc.
    • Los Angeles, California, United States, 90057
      • National Research Institute - Panorama
    • Oceanside, California, United States, 92056
      • Excell Research
    • Sacramento, California, United States, 95821
      • Northern California Research
    • Sacramento, California, United States, 95821
      • Clinical Trials Research
    • San Diego, California, United States, 92108
      • Wake Research Associates, LLC
    • San Diego, California, United States, 92111
      • Women's Healthcare Affiliates
    • Santa Ana, California, United States, 92705
      • CITrials, Inc
    • Thousand Oaks, California, United States, 91360
      • Millennium Clinical Trials
    • Upland, California, United States, 91786
      • Women's Medical Group of Upland
    • Valley Village, California, United States, 91607
      • Bayview Research Group
  • Colorado
    • Denver, Colorado, United States, 80209
      • Downtown Women's Health Care
    • Denver, Colorado, United States, 80220
      • Horizons Clincial Research Center LLC
  • 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
    • Clearwater, Florida, United States, 33757
      • Olympian Clinical Research
    • Coral Springs, Florida, United States, 33065
      • Precision Clinical Research
    • Crystal River, Florida, United States, 34429
      • Nature Coast Clinical Research
    • 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
    • Gainesville, Florida, United States, 32607
      • Florida Medical Research
    • Hialeah, Florida, United States, 33016
      • Vital Pharma Research Inc.
    • Jupiter, Florida, United States, 33458
      • Health Awareness
    • 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, 33126
      • LCC Medical Research Institute, LLC
    • Miami, Florida, United States, 33134
      • Medical Research Center of Miami II
    • Miami, Florida, United States, 33176
      • Spotlight research center
    • Miami, Florida, United States, 33144
      • Medical Research Centers of South Florida, Inc.
    • Miami, Florida, United States, 33174
      • Florida International Research Center
    • Miami, Florida, United States, 33186
      • Med Research Of Florida, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • North Miami, Florida, United States, 33161
      • Healthcare Clinical Data Inc
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare LLC
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc
    • Orlando, Florida, United States, 32822
      • Cornerstone Research Institute
    • Orlando, Florida, United States, 32808
      • Omega Research Consultants
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Palm Harbor, Florida, United States, 34684
      • Sunset Point Medical Associates
    • Pinellas Park, Florida, United States, 33781
      • Radiant Research
    • Ponte Vedra, Florida, United States, 32081
      • St. Johns Center for Clinical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Port Saint Lucie, Florida, United States, 34952
      • Health Awareness
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
    • Tampa, Florida, United States, 33614
      • GCP Clinical Research, LLC
    • The Villages, Florida, United States, 32159
      • Premier Medical Associates
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • AGILE Clinical Research Trials, LLC
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta LLC
    • Duluth, Georgia, United States, 30096
      • NuDirections Clinical Research
    • Riverdale, Georgia, United States, 30274
      • Infinite Clinical Trials
    • Sandy Springs, Georgia, United States, 30328
      • WR-Mount Vernon Clinical Research
    • Snellville, Georgia, United States, 30078
      • Georgia Clinical Research
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rosemark Women Care Specialists
    • Idaho Falls, Idaho, United States, 83404
      • The Healing Sanctuary, LLC
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Womens Health USA, Inc.
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research Institute
  • Indiana
    • Brownsburg, Indiana, United States, 46254
      • Investigators Research Group, LLC
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Cypress Medical Research Center
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Avant Research Associates, LLC
    • Marrero, Louisiana, United States, 70072
      • Praetorian Pharmaceutical Research
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
    • Metairie, Louisiana, United States, 70001
      • Southern Clinical Research Associates
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research Inc
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Bay State Clinical Trials, 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
    • Las Vegas, Nevada, United States, 89104-3218
      • Clinical Research Center of Nevada (CRCN)
    • Las Vegas, Nevada, United States, 89128
      • Dr.R. Garn Mabey, MD,Office Of
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute, LLC
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OBGYN Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87109-4640
      • Bosque Women's Care
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
    • West Seneca, New York, United States, 14224
      • Circuit Clinical
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC
    • Durham, North Carolina, United States, 27714
      • Carolina Women's Research and Wellness Center
    • Fayetteville, North Carolina, United States, 28304
      • Carolina Insitute for Clinical Research
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research
    • Hickory, North Carolina, United States, 28601
      • PMG Research of Hickory, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27607
      • Unified Women's 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, 45227
      • CTI
    • Cincinnati, Ohio, United States, 45267
      • Greater Cincinnati OB/GYN
    • Columbus, Ohio, United States, 43231
      • Complete Healthcare For Women
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc.
    • Englewood, Ohio, United States, 45322
      • HWC Women's Research Center
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research, Inc
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • OB-GYN Associates
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center LLC
    • Philadelphia, Pennsylvania, United States, 19114
      • Philadelphia Clinical Research, LLC
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga GYN-Oncology
    • Chattanooga, Tennessee, United States, 37421
      • WR Clinsearch, LLC
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc
    • Memphis, Tennessee, United States, 38120
      • Medical Research Center of Memphis, LLC
    • Murfreesboro, Tennessee, United States, 37130
      • International Clinical Research
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research - Georgetown
    • Beaumont, Texas, United States, 77702
      • Gadolin Research, LLC
    • Bryan, Texas, United States, 77802
      • DiscoveResarch, Inc.
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
    • Houston, Texas, United States, 77030
      • Advances In Health
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research, LLC
    • Lampasas, Texas, United States, 76550
      • FMC Science
    • Plano, Texas, United States, 75024
      • ClinRx Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research Centers, Inc.
    • Sugar Land, Texas, United States, 77478
      • Excel Clinical Research, LLC
  • Utah
    • Murray, Utah, United States, 84123
      • Epic Medical Research
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
    • Salt Lake City, Utah, United States, 84107
      • Advanced Clinical Research-Old Farm OB/GYN (Utah)
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads Inc
    • Virginia Beach, Virginia, United States, 23456
      • Tidewater Clinical Research, Inc.
  • Washington
    • Seattle, Washington, United States, 98115
      • Seattle Women's: Health, Research, Gynecology

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 > 40 IU/L), or
  • Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
• Subject is seeking treatment for relief for VMS associated with menopause.
• Subject is in good general health as determined on the basis of medical history and general physical examination, including a bimanual clinical pelvic examination and clinical breast examination devoid of relevant clinical findings, performed at the screening visit; hematology and biochemistry parameters; pulse rate and/or blood pressure; and ECG within the reference range for the population studied, or showing no clinically relevant deviations.
• Subject has documentation of a normal/negative or no clinically significant mammogram findings (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). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit.
• Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT) or the ED visit for subjects who are withdrawn from the study prior to completion, and any time during the study in the case of uterine bleeding. 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 [CYP] 1A2 inhibitors, hormone replacement therapy [HRT], hormonal contraceptive, any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue such drugs for the full extent of the study.
• Subject has a known substance abuse or alcohol addiction within 6 months of screening.
• Subject has 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 a 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 x ULN; or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula ≤ 59 mL/min per 1.73 m^2 at the screening visit.
• 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 questions 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, as assessed at screening and at the time of visit 2 (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 a 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fezolinetant 30 mg; Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, once daily (QD) for a period of 52 Weeks.	Drug: fezolinetant; administered orally
Experimental: Fezolinetant 45 mg; Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD for a period of 52 Weeks.	Drug: fezolinetant; administered orally
Placebo Comparator: Placebo; Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, QD for a of period of 52 Weeks.	Drug: placebo; administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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 this treatment. An AE can therefore be any unfavorable & unintended sign, symptom, or disease temporally associated with the use of medicinal product (MP) whether or not considered related to 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. A TEAE is defined as an AE observed after starting administration of study drug & 21 days after the last dose of study drug.	From first dose of study drug until 21 days after last dose of study drug (Up to 55 weeks)
Number of Participants With Mild, Moderate and Severe TEAE	An adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. A TEAE is defined as an AE observed after starting administration of the study drug and 21 days after the last dose of study drug. Severity of AE we were classified as Mild: No disruption of normal daily activities; Moderate: Affect normal daily activities; and Severe: Inability to perform daily activities.	From first dose of study drug until 21 days after last dose of study drug (Up to 55 weeks)
Percentage of Participants With Endometrial Hyperplasia	Endometrial hyperplasia was confirmed from the endometrial biopsy report.	Baseline Up to 52 weeks
Percentage of Participants With Endometrial Cancer	Endometrial cancer was confirmed from the endometrial biopsy report.	Baseline Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Endometrial Thickness at Week 52	Endometrial thicness was obtained from the transvaginal ultrasound. The endometrium was measured in the long axis or sagittal plane. The measurement was of the thickest echogenic area from 1 basal endometrial interface across the endometrial canal to the other basal surface.	Baseline and week 52
Percentage of Participants With Disordered Proliferative Endometrium	Disordered proliferative endometrium was confirmed from the endometrial biopsy report.	Baseline Up to 52 weeks
Change From Baseline in Bone Mineral Density (BMD) at Hip at Week 52	Changes in BMD hip was assessed by dual-energy X-ray absorptiometry (DXA) scan.	Baseline and week 52
Change From Baseline in Trabecular Bone Score (TBS) at Hip at Week 52	TBS was a bone texture assessment that serves as a substitute for bone microarchitecture and predicts fracture risk independent of BMD and clinical risk factors. The DXA imaging was processed and analyzed as it would normally be and then evaluated using an automated algorithm to determine the TBS. T-score ≥1.350 was considered to be normal; T-score between 1.200 and 1.350 is considered to be consistent with partially degraded microarchitecture; and T-score ≤1.200 defines degraded microarchitecture.	Baseline and week 52
Change From Baseline in BMD at Spine at Week 52	Changes in BMD spine was assessed by DXA scan.	Baseline and week 52
Change From Baseline in TBS at Spine at Week 52	TBS was a bone texture assessment that serves as a substitute for bone microarchitecture and predicts fracture risk independent of BMD and clinical risk factors. The DXA imaging was processed and analyzed as it would normally be and then evaluated using an automated algorithm to determine the TBS. T-score ≥1.350 was considered to be normal; T-score between 1.200 and 1.350 is considered to be consistent with partially degraded microarchitecture; and T-score ≤1.200 defines degraded microarchitecture.	Baseline and week 52
Number of Participants With Suicidal Ideation and/or Behaviour as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS assessed the risk for suicidal behavior and suicide ideation. Participants responded as "Yes" or "No" 10 items. Suicidal ideation (1. Wish to be dead; 2. Non-specific active suicidal thoughts; 3. Active suicidal ideation with any methods (not plan) without intent to act; 4. Active suicidal ideation with some intent to act, without specific plan; 5. Active suicidal ideation with specific plan and intent; ). Suicidal behaviour (1. Preparatory acts or behavior 2. Aborted attempt 3. Interrupted attempt 4. Actual attempt 5. Completed suicide). Participants with 'Yes' to any one of the above 10 questions for suicidal ideation and behavior were reported.	Baseline, week 12, week 24, week 52 and follow-up (week 55)
Number of Participants With Self-injurious Behavior Without Suicidal Intent as Assessed by C-SSRS	The C-SSRS assessed the risk for Self-injurious Behavior without Suicidal Intent. Question was asked "Has participant engaged in Non-Suicidal Self-Injurious Behavior?". Participants with 'yes' to the question were reported.	Baseline, week 12, week 24, week 52 and follow-up (week 55)

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

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2019
• Primary Completion (Actual): January 4, 2022
• Study Completion (Actual): January 4, 2022

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 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 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-0304; 2019-000275-16 (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