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Hot FlashesPhase 3Skylight 1NCT04003155

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

A Phase 3 study testing fezolinetant in people with Hot Flashes, run by Astellas Pharma Global Development, Inc. at 96 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 40 to 65 years, women only
Conditions the study is for
Hot Flashes
What is being tested?
fezolinetant
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
527 participants
Where
96 sitesin 7 countries
Study dates
11 Jul 2019to 11 Aug 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

96 sites in 7 countries.

96 sites in 7 countries

United States72 sites

  • Accent Clinical Research Professionals

    Allen, Texas, 75013

  • SEC Clinical Research

    Andalusia, Alabama, 36420

  • Better Health Greater Life

    Atlanta, Georgia, 30312

  • Advanced Clinical Research - Rancho Paseo

    Banning, California, 92220

  • Central Research Associates

    Birmingham, Alabama, 59405

  • DiscoveResarch, Inc.

    Bryan, Texas, 77802

  • Gwinnett Research Institute

    Buford, Georgia, 30519

  • Hope Clinical Research, LLC

    Canoga Park, California, 91303

  • Alliance Research Inc

    Canoga Park, California, 91304

  • Velocity Clinical Research

    Cincinnati, Ohio, 45242

  • IACT Health

    Columbus, Georgia, 31904

  • Complete Healthcare For Women

    Columbus, Ohio, 43231

  • Precision Clinical Research

    Coral Springs, Florida, 33065

  • Avant Research Associates, LLC

    Crowley, Louisiana, 70526

  • American Research Institute, Inc.

    Cutler Bay, Florida, 33157

  • Avail Clinical Research, LLC

    DeLand, Florida, 32720

  • Universal Axon Clinical Research

    Doral, Florida, 33166

  • NuDirections Clinical Research

    Duluth, Georgia, 30096

  • Achieve Clinical Research, LLC

    Ensley, Alabama, 35218

  • Lillestol Research, LLC

    Fargo, North Dakota, 58104

  • Fleming Island Center for Clinical Research

    Fleming Island, Florida, 32003

  • Clinical Physiology Associates

    Fort Myers, Florida, 33912

  • Unified Women's Clinical Research

    Greensboro, North Carolina, 27408

  • Vital Pharma Research Inc.

    Hialeah, Florida, 33016

  • Marvel Clinical Research

    Huntington Beach, California, 92647

  • Protenium Clinical Research, LLC

    Hurst, Texas, 76054

  • The Healing Sanctuary, LLC

    Idaho Falls, Idaho, 83404

  • Health Awareness

    Jupiter, Florida, 33458

  • GYN Research Center

    Kissimmee, Florida, 34741

  • Grossmont Center for Clinical Research

    La Mesa, California, 91942

  • Centex Studies, Inc.

    Lake Charles, Louisiana, 70601

  • Multi-Specialty Research Associates, Inc.

    Lake City, Florida, 32055

  • Altus Research

    Lake Worth, Florida, 33461

  • Excel Clinical Research, LLC

    Las Vegas, Nevada, 89109

  • Office Of Edmond Pack, Md

    Las Vegas, Nevada, 89113

  • Ocean State Clinical Research Partners

    Lincoln, Rhode Island, 02865

  • National Research Institute - Panorama

    Los Angeles, California, 90057

  • Medical Research Center of Memphis LLC

    Memphis, Tennessee, 38120

  • Medical Research Center of Miami II

    Miami, Florida, 33134

  • Spotlight research center

    Miami, Florida, 33176

  • New Age Medical Research Corporation

    Miami, Florida, 33186

  • Montana Medical Research Inc

    Missoula, Montana, 59801

  • Coastal Carolina Research Center

    Mt. Pleasant, South Carolina, 29464

  • International Clinical Research

    Murfreesboro, Tennessee, 37130

  • EPIC Medical Research

    Murray, Utah, 84123

  • Coastal Connecticut Research, LLC

    New London, Connecticut, 06320

  • Suncoast Clinical Research, Inc.

    New Port Richey, Florida, 34652

  • Neuro-Behavioral Clinical Research, Inc

    North Canton, Ohio, 44720

  • Coastal Carolina Research Center

    North Charleston, South Carolina, 29406

  • Quality Clinical Research, Inc

    Omaha, Nebraska, 68114

  • Clinical Neuroscience Solutions, Inc

    Orlando, Florida, 32801

  • Clinical Neuroscience Solutions, Inc

    Orlando, Florida, 32806

  • Cornerstone Research Institute

    Orlando, Florida, 32822

  • Philadelphia Clinical Research, LLC

    Philadelphia, Pennsylvania, 19114

  • Elite Clinical Studies, LLC

    Phoenix, Arizona, 85018

  • St. Johns Center for Clinical Research

    Ponte Vedra, Florida, 32081

  • Health Awareness

    Port Saint Lucie, Florida, 34952

  • Unified Womens Clinical Research

    Raleigh, North Carolina, 27607

  • Wake Research Associates, LLC

    Raleigh, North Carolina, 27612

  • Infinite Clinical Trials

    Riverdale, Georgia, 30274

  • Rochester Clinical Research, Inc.

    Rochester, New York, 14609

  • Northern California Research

    Sacramento, California, 95821

  • Saginaw Valley Medical Research Group, Llc

    Saginaw, Michigan, 48604

  • Precision Research Institute, Inc

    San Diego, California, 92114

  • International Clinical Research

    Sanford, Florida, 32771

  • Palmetto Clinical Research

    Summerville, South Carolina, 29485

  • Premier Medical Associates

    The Villages, Florida, 32159

  • Eclipse Clinical Research

    Tucson, Arizona, 85745

  • Tidewater Clinical Research, Inc.

    Virginia Beach, Virginia, 23456

  • Emerson Clinical Research Institute

    Washington D.C., District of Columbia, 20011

  • Invocare Clinical Research Center

    West Columbia, South Carolina, 29169

  • Unified Women's Clinical Research

    Winston-Salem, North Carolina, 27103

Other trials in United States

Poland9 sites

  • Site PL48003

    Bialystok, 15-224

  • Site PL48012

    Katowice, Silesian Voivodeship, 40-648

  • Site PL48013

    Katowice, 40-301

  • Site PL48004

    Katowice, 40-611

  • Site PL48007

    Lublin, 20362

  • Site PL48005

    Poznan, 60-848

  • Site PL48014

    Świdnik, 21040

  • Site PL48009

    Warsaw, 02-679

  • Site PL48001

    Warsaw, 02-798

Other trials in Poland

Canada5 sites

  • Site CA15003

    Brampton, Ontario, L6T 0G1

  • Site CA15002

    Point Claire, Quebec, H9R 4S3

  • Site CA15001

    Québec, Quebec, G1N 4V3

  • Site CA15004

    Québec, Quebec, G1W 4R4

  • Site CA15006

    Québec, Quebec, G3K 2P8

Other trials in Canada

United Kingdom4 sites

  • Site GB44002

    Coventry, Warwickshire, CV3 4FJ

  • Site GB44004

    Middlesex, HA6 2RN

  • Site GB44003

    Orpington, Kent, BR5 3QG

  • Site GB44001

    Wokingham, Berkshire, RG40 1XS

Other trials in United Kingdom

Hungary3 sites

  • Site HU36004

    Debrecen, 4024

  • Site HU36001

    Kecskemét, 6000

  • Site HU36002

    Szekesfeherver, 8000

Other trials in Hungary

Czechia2 sites

  • Site CZ42001

    Olomouc, 772 00

  • Site CZ42003

    Vodňany, South Bohemian Region, 389 01

Other trials in Czechia

Spain1 site

  • Site ES34004

    Seville, 41018

Other trials in Spain

About this study

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

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.

Read the detailed description

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

Conditions
Hot Flashes
Being tested
fezolinetant, placebo
Keywords
menopause, ESN364, vasomotor symptoms, fezolinetant
Medical subject headings
Hot Flashes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fezolinetantDrug

    Oral Tablet

  • placeboDrug

    Oral Tablet

Study groups in NCT04003155
Study groupRoleWhat they receive
Double-blind Period: PlaceboPlacebo comparatorParticipants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.
Receives: Drug: placebo
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mgExperimentalParticipants 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.
Receives: Drug: fezolinetant
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mgExperimentalParticipants 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.
Receives: Drug: fezolinetant
Double-blind Period: Placebo /Extension Period: Fezolinetant 30 mgExperimentalParticipants 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.
Receives: Drug: fezolinetant
Double-blind Period: Placebo /Extension Period: Fezolinetant 45 mgExperimentalParticipants 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.
Receives: Drug: fezolinetant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and week 4

  2. 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.

    Measured: Baseline and week 12

  3. 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.

    Measured: Baseline and week 4

  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.

    Measured: Baseline and week 12

Secondary outcomes (10)

  1. 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.

    Measured: Baseline and week 12

  2. 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.

    Measured: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11

  3. 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.

    Measured: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11

  4. 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.

    Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

  5. 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.

    Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

  6. 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.

    Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

  7. 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.

    Measured: 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)

  8. 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.

    Measured: Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)

  9. 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.

    Measured: Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)

  10. 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.

    Measured: From first dose date up to 21 days after last dose (to 55 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2019
  2. Study start11 Jul 2019
  3. Primary completion29 Oct 2020
  4. Study completion11 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
527 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04003155
Sponsor's protocol ID
2693-CL-0301
Other IDs
2018-003528-35, 2018
Acronym
Skylight 1
Status last verified
Oct 2024
First submitted
27 Jun 2019
Last updated
4 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • Shapiro C M M, Neal-Perry G, Stute P, Thurston RC, Wolfman W, English M, Wu X, Ottery FD. Early onset, maintenance of effect, and day-/night-time findings following fezolinetant treatment for moderate to severe vasomotor symptoms associated with menopause: A pooled phase 3 analysis. Maturitas. 2025 Dec;203:108740. doi: 10.1016/j.maturitas.2025.108740. Epub 2025 Oct 6.

    PubMed 41259888

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

    PubMed 40044127

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

    PubMed 39739195

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

    PubMed 38775925

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

    PubMed 38396203

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

    PubMed 37990323

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

    PubMed 37870510

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

    PubMed 36924778

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing fezolinetant in people with Hot Flashes, run by Astellas Pharma Global Development, Inc. at 96 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Poland, Canada, United Kingdom, Hungary and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4 (time frame: Baseline and week 4). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04003155, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2024.

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