MenopausePhase 2NCT03192176

A Dose-ranging Study of the Efficacy of ESN364 in Postmenopausal Women Suffering Vasomotor Symptoms (Hot Flashes)

A Phase 2 study testing Fezolinetant in people with Menopause and Hot Flashes, run by Astellas Pharma Global Development, Inc. at 51 sites in United States.

Completed

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

Official record

Search all trials

Trial summary

This study determined the effects of different doses and dosing regimens of ESN364 on the frequency and severity of hot flashes. The treatment was administered for 12 weeks to postmenopausal women, aged 40 to 65, suffering at least 50 moderate to severe hot flashes per week. Read more about this study

Who is it for?: Ages 40 to 65 years, women only
Conditions the study is for: Menopause, 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: 356 participants
Where: 51 sitesUnited States
Study dates: 19 Jul 2017to 19 Sep 2018
Phase: Phase 2
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

Women >40 years and ≤65 years of age at the screening visit;
A body mass index between 18 kg/sqm to 38 kg/sqm (extremes included);
Spontaneous amenorrhea for ≥12 consecutive months; or 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 (with or without hysterectomy);
At least 50 moderate to severe vasomotor symptoms per week (ie, 7 consecutive days), as recorded in the daily diary during the screening period;
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, as judged by the Investigator;
Women >40 years of age who have documentation of a normal/negative or no clinically significant findings mammogram (obtained at Screening or within the prior 9 months of trial enrollment.) Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic findings;

Show all 13Show fewer

Willing to undergo a transvaginal ultrasound to assess endometrial thickness at Screening and at Week 12 (end-of-treatment, - and subjects) who are withdrawn from the study prior to completion, at the Early Termination (ET) Visit. This is not required for subjects who have had a partial (supracervical) or full hysterectomy;
Willing to undergo an endometrial biopsy at Screening (in the event that the subject's transvaginal ultrasound shows endometrial thickness ≥4 mm) and at Week 12 (end--of--treatment) - all subjects), for subjects with uterine bleeding, and for subjects who are withdrawn from the study prior to completion, at the ET Visit if study drug exposure is ≥10 weeks. This is not required for subjects who have had a partial (supracervical) or full hysterectomy;
Negative alcohol breath test and negative urine test for selected drugs of abuse (amphetamines, tricyclic antidepressants, cocaine, or opiates) at the screening visit;
Negative urine pregnancy test;
Negative serology panel (including hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody screens);
Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; and
Documentation of a normal Pap smear (or equivalent cervical cytology) or of no clinical significance in the opinion of the Investigator within the previous 9 months or at Screening.

Who cannot join

Use of a prohibited therapy (hormone therapy, hormonal contraceptive, or vasomotor symptom medication [prescription, over the counter, or herbal]) or not willing to wash out drugs
History (in the past year) or presence of drug or alcohol abuse;
Previous or current history of a malignant tumor, except for basal cell carcinoma;
Uncontrolled hypertension and a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg;
Judged by the Investigator to be unsuited to participate in the study based on findings observed during physical examination, vital sign assessment, or 12-lead electrocardiogram (ECG);
History of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;

Show all 17Show fewer

An unacceptable result from endometrial biopsy (performed when endometrial thickness is ≥ 4mm measured by transvaginal ultrasound) of endometrial hyperplasia, endometrial cancer, or inadequate specimen at Screening (1 repeat biopsy permitted if technically possible);
History of endometrial hyperplasia or uterine/endometrial cancer;
History of unexplained uterine bleeding;
History of seizures or other convulsive disorders;
Medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [eg, moderate asthma], endocrine, or gynecological disease) or malignancy that could confound interpretation of the study outcome;
Presence or sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion (ADME) mechanisms of drugs as judged by the Investigator;
Active liver disease or jaundice, or values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 x the upper limit of normal (ULN); or total bilirubin >1.5 x ULN; or creatinine >1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula ≤59 mL/min/1.73 sqm at the screening visit;
Concurrent participation in another interventional study (or participation within 3 months prior to screening in this study);
Suicide attempt in the past 3 years;
Unable or unwilling to complete the study procedures; or
Subject is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof, who is directly involved in the conduct of the study.

Trial locations and contacts

51 sites in 1 country.

City, postcode or hospital

51 sites in 1 country

United States51 sites

Research Site
Anniston, Alabama, 36207
Research Site
Atlanta, Georgia, 30312
Research Site
Birmingham, Alabama, 35205
Research Site
Champaign, Illinois, 61820
Research Site
Charlottesville, Virginia, 22911
Research Site
Cincinnati, Ohio, 45267
Research Site
Clarksville, Tennessee, 37040
Research Site
Cleveland, Ohio, 44122
Research Site
Columbus, Ohio, 43210
Research Site
Columbus, Ohio, 43213
Research Site
Crystal River, Florida, 34429
Research Site
DeLand, Florida, 32720
Research Site
Denver, Colorado, 80209
Research Site
Elkridge, Maryland, 21075
Research Site
Houston, Texas, 77058
Research Site
Hurst, Texas, 76054
Research Site
Jupiter, Florida, 33458
Research Site
Kingsport, Tennessee, 37660
Research Site
Lake Worth, Florida, 33461
Research Site
Lampasas, Texas, 76550
Research Site
Las Vegas, Nevada, 89123
Research Site
Lincoln, Nebraska, 68510
Research Site
Los Angeles, California, 90057
Research Site
Marrero, Louisiana, 70072
Research Site
Meridian, Idaho, 83642
Research Site
Miami, Florida, 33144
Research Site
Milford, Connecticut, 06460
Research Site
Mt. Pleasant, South Carolina, 29464
Research Site
New York, New York, 10032
Research Site
Norcross, Georgia, 30092
Research Site
Norfolk, Nebraska, 68701
Research Site
Oceanside, California, 92056
Research Site
Oklahoma City, Oklahoma, 73112
Research Site
Ormond Beach, Florida, 32174
Research Site
Panorama City, California, 91402
Research Site
Philadelphia, Pennsylvania, 19140
Research Site
Phoenix, Arizona, 85023
Research Site
Plano, Texas, 75093
Research Site
Port Saint Lucie, Florida, 34952
Research Site
Riverton, Utah, 84065
Research Site 052
Sacramento, California, 95821
Research Site 058
Sacramento, California, 95821
Research Site
San Antonio, Texas, 78229
Research Site
San Diego, California, 92114
Research Site
Seattle, Washington, 98105
Research Site
Spokane, Washington, 99207
Research Site
Thousand Oaks, California, 91360
Research Site
Valley Village, California, 91607
Research Site
Vienna, Virginia, 22182
Research Site
Watertown, Massachusetts, 02472
Research Site
Williamsville, New York, 14221

Other trials in United States

About this study

Official title: A Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging, Phase 2b Study to Investigate the Efficacy of ESN364 in Postmenopausal Women Suffering From Vasomotor Symptoms (Hot Flashes)

Read the detailed description

This was a 12-week randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multi-center study to assess the efficacy of ESN364 in postmenopausal women suffering from vasomotor symptoms (hot flashes).

This study consisted of a screening period (Days -35 to -1, including the screening visit [Visit 1] and a minimum 7-day collection of baseline vasomotor symptom frequency and severity assessments), a 12 week treatment period (Day 1 [Visit 2] to Week 12 [Visit 5]), and a follow up visit (Week 15 [Visit 6]) 3 weeks after the last dose of study drug.

The study was performed on an ambulatory basis. The screening visit (Visit 1) occurred up to 35 days prior to randomization. Eligibility was assessed via physical examination, clinical laboratory testing, vital signs, ECG, Pap smear, mammography, and endometrial biopsy. Subjects received an electronic diary to record daily vasomotor symptoms during the duration of the screening period. Subjects who had ≥7 consecutive days of vasomotor symptom recordings participated in the study. Subjects are encouraged to continue recording for the duration of the whole screening period. The electronic diary was reviewed by study site staff on Day 1 (Visit 2) to confirm study eligibility. Subjects were rescreened 1 time upon approval of the medical monitor.

During the treatment period, subjects returned to the study site every 4 weeks for assessments.

The follow-up visit occurred approximately 3 weeks following the last dose of study drug.

Conditions: Menopause, Hot Flashes
Being tested: Fezolinetant, Placebo
Keywords: Vasomotor symptoms, Menopause, Hot flashes, Perimenopause
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
Also called ESN364
Oral Capsule
PlaceboDrug
Oral Capsule

Study groups in NCT03192176
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 15 mg	Experimental	Participants received fezolinetant 15 mg capsules orally, BID for a period of 12 weeks. Receives: Drug: Placebo
Fezolinetant 30 mg	Experimental	Participants received fezolinetant 30 mg capsules orally, BID for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 60 mg	Experimental	Participants received fezolinetant 60 mg capsules orally, BID for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 90 mg	Experimental	Participants received fezolinetant 90 mg capsules orally, BID for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 30 mg + Placebo	Experimental	Participants received fezolinetant 30 mg capsules orally, QD and matching placebo QD for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 60 mg + Placebo	Experimental	Participants received fezolinetant 60 mg capsules orally, QD and matching placebo QD for a period of 12 weeks. Receives: Drug: Fezolinetant
Fezolinetant 120 mg + Placebo	Experimental	Participants received fezolinetant 120 mg capsules orally, QD and matching placebo QD for a period of 12 weeks. Receives: Drug: Fezolinetant

What is being measured

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

Co-Primary Efficacy Endpoint: Change From Baseline (CFB) in The Mean Frequency of Moderate to Severe Vasomotor Symptoms (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 and severity 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 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).
Measured: Baseline and week 4
Co-Primary Efficacy Endpoint: 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 and severity 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 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).
Measured: Baseline and week 12
Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4
Severity of moderate to severe VMS per day was calculated as follows:
[(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS.
Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 moderate or severe VMS. Higher score indicates greater severity.
Measured: Baseline and week 4
Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12
Severity of moderate to severe VMS per day was calculated as follows:
[(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS.
Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 moderate or severe VMS. Higher scores indicates greater severity.
Measured: Baseline and week 12

Secondary outcomes (32)

Change From Baseline in The Mean Frequency of Mild, Moderate, and Severe VMS to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, subject does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Mean Frequency of Moderate and Severe VMS to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15
Change From Baseline in The Mean Severity of Mild, Moderate, and Severe VMS to Each Study Week
Severity of mild, moderate \& severe VMS per day was calculated as follows
[(number of mild VMS × 1) + (number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily mild/moderate/severe VMS
Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant did not wake up but later noticed damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 \& was sweating \& needed to take action Severity was zero for participants that had no moderate or severe VMS. Higher score indicates greater severity.
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Mean Severity of Moderate and Severe VMS to Each Study Week
Severity of moderate to severe VMS per day was calculated as follows:
[(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS.
Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 patients that had no moderate or severe VMS. Higher score indicates greater severity.
Measured: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15
Change From Baseline in The Hot Flash Score of Mild, Moderate, and Severe VMS to Each Study Week
The hot flash score per 24h (or 12 h day time or 12 h night time) of VMS (mild, moderate, and severe) is calculated as follows:
(number of mild VMS x 1) + (number of moderate VMS x 2) + (number of severe VMS x 3).
Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant did not wake up but later noticed damp sheets or clothing.
Moderate VMS was defined as sensation of heat with sweating/dampness, but 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). Higher score indicates greater severity.
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Hot Flash Score of Moderate and Severe VMS to Each Study Week
The hot flash score per 24h of moderate and severe VMS is calculated as follows:
(number of moderate VMS x 2) + (number of severe VMS x 3).
Moderate VMS was defined as sensation of heat with sweating/dampness, but 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). VMS. Baseline is the average frequency of 24h vasomotor symptom from 7 non-missing days prior to Day 1. Higher score indicates greater severity.
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Mean Percent Reduction of Mild, Moderate, And Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, subject does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Mean Percent Reduction of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 50% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
Number of Participants With Mean Percent Reduction of 70% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 90% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 50% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 70% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 90% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 2 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 3 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 4 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 5 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of mild, moderate and severe VMS was the number of mild, moderate and severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Mild VMS was defined as sensation of heat without sweating/dampness. If at night, participant does not wake up but later notices damp sheets or clothing. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 2 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 3 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 4 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 5 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) at Weeks 4, 8, 12, and 15
The HFRDIS is a 10-item scale that measures a woman's perceptions of the degree to which VMS interfere with 9 daily life activities (work, social activities, leisure, sleep, mood, concentration, relations with others, sexuality, and enjoying life); the tenth item measures interference with overall quality of life. This scale was modeled after items on the Brief Pain Inventory and Brief Fatigue Inventory, which assess the extent to which pain or fatigue interfere with daily life. Participants were asked to rate the extent to which VMS had interfered with each item during the previous 2-week time interval using a 0 (do not interfere) to 10 (completely interfere) scale. Overall mean score is the average of individual item scores (sum of items/10).
Measured: Baseline and weeks 4, 8, 12, and 15
Leeds Sleep Evaluation Questionnaire (LSEQ) Domain Scores at Weeks 4, 8, 12 and 15
The LSEQ is a 10-item self-rated questionnaire that assesses a participants aspects of sleep and early morning behavior. The questions are grouped into 4 chronological areas: ease of getting to sleep, perceived quality of sleep, ease of awaking from sleep, and integrity of early morning behavior following wakefulness. The LSEQ is a visual analog scale that requires respondents to place marks on a group of 10 cm lines. Lines extend between extremes like "more difficult than usual" and "easier than usual." Responses are measured using a 100 mm scale and are averaged to a score for each domain. Higher scores indicates better sleep and better early morning behavior.
Measured: Weeks 4, 8, 12, and 15
Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8, 12, and 15
The GCS is a 21-item scale that provides a brief but comprehensive and valid measure of climacteric symptomatology. Each item is rated by the participant according to its severity using a 4-point rating scale from 0 (none) to 3 (severe). The first 20 items of the scale combine into 3 main independent symptom measures by summing up the individual item scores: psychological symptoms (items 1 to 11; score 0 to 33), physical symptoms (items 12 to 18; score 0 to 21), and VMS (items 19 to 20; score 0 to 6). Item 21 is a probe for sexual dysfunction. The total score can range from 0 to 63. Higher scores indicate worse symptoms.
Measured: Baseline and weeks 4, 8, 12, and 15
Change From Baseline in Menopause-Specific Quality of Life (MENQoL) at Weeks 4, 8, 12, and 15
The MENQoL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of 1 of 4 domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1 to 3), psychosocial (items 4 to 10), physical (items 11 to 26), and sexual (items 27 to 29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a 0 (not bothersome) to 6 (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a "1" and endorsement a "2," plus the number of the particular rating, so that the possible score on any item ranges from 1 to 8. Higher scores indicate that menopause symptoms are more bothersome.
Measured: Baseline and weeks 4, 8, 12, and 15
Change Over Time From Baseline in Plasma Concentrations of Luteinizing Hormone (LH) at Week 12
Change was calculated as the post-baseline measurement minus the baseline measurement. Baseline was the last measurement taken prior to initial study drug administration.
Measured: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Follicle-Stimulating Hormone (FSH) at Week 12
Change was calculated as the post-baseline measurement minus the baseline measurement. Baseline was the last measurement taken prior to initial study drug administration.
Measured: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Estradiol (E2) at Week 12
Change was calculated as the post-baseline measurement minus the baseline measurement. Baseline was the last measurement taken prior to initial study drug administration. The analysis value for Estradiol was imputed as 73.4/2 = 36.7 when result was < 73.4.
Measured: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Sex Hormone-Binding Globulin (SHBG) at Week 12
Change was calculated as the post-baseline measurement minus the baseline measurement. Baseline was the last measurement taken prior to initial study drug administration.
Measured: Baseline and week 12

Timeline

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

19 Jul 201719 Sep 2018

First posted19 Jun 2017
Study start19 Jul 2017
Primary completion19 Sep 2018
Study completion19 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for MenopauseStudies of the same condition, open and under way.
More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 356 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03192176
Sponsor's protocol ID: ESN364_HF_205
Status last verified: Nov 2024
First submitted: 15 Jun 2017
Last updated: 26 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N, Lee M, Skillern L, Ramael S. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020 Apr;27(4):382-392. doi: 10.1097/GME.0000000000001510.
PubMed 32102086

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruiting
The Role of Diet Quality in Sleep Among Women in Postmenopause
Post Menopausal Women
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruiting
Effect of Hormone Replacement Therapy on Physiotherapy Outcomes in Postmenopausal Women With Frozen Shoulder
Frozen Shoulder, Adhesive Capsulitis
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer

All Menopause trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging, Phase 2b Study to Investigate the Efficacy of ESN364 in Postmenopausal Women Suffering From Vasomotor Symptoms (Hot Flashes)
ClinicalTrials.gov ID: NCT03192176
Acronym / sponsor ID: ESN364_HF_205
Conditions: Menopause, Hot Flashes
Keywords: Vasomotor symptoms, Menopause, Hot flashes, Perimenopause
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 356 participants (actual)
Lead sponsor: Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
Study start: 19 Jul 2017 (actual)
Primary completion: 19 Sep 2018 (actual)
Study completion: 19 Sep 2018 (actual)
First posted: 19 Jun 2017 (actual)
Results: Posted 29 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

During the treatment period, subjects returned to the study site every 4 weeks for assessments.

The follow-up visit occurred approximately 3 weeks following the last dose of study drug.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 8

Arm	Type	Receives
Placebo	Placebo comparator	Drug: FezolinetantParticipants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks.
Fezolinetant 15 mg	Experimental	Drug: PlaceboParticipants received fezolinetant 15 mg capsules orally, BID for a period of 12 weeks.
Fezolinetant 30 mg	Experimental	Drug: FezolinetantParticipants received fezolinetant 30 mg capsules orally, BID for a period of 12 weeks.
Fezolinetant 60 mg	Experimental	Drug: FezolinetantParticipants received fezolinetant 60 mg capsules orally, BID for a period of 12 weeks.
Fezolinetant 90 mg	Experimental	Drug: FezolinetantParticipants received fezolinetant 90 mg capsules orally, BID for a period of 12 weeks.
Fezolinetant 30 mg + Placebo	Experimental	Drug: FezolinetantParticipants received fezolinetant 30 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.
Fezolinetant 60 mg + Placebo	Experimental	Drug: FezolinetantParticipants received fezolinetant 60 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.
Fezolinetant 120 mg + Placebo	Experimental	Drug: FezolinetantParticipants received fezolinetant 120 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.

Who may qualify

Ages: 40 to 65 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Women >40 years and ≤65 years of age at the screening visit;
A body mass index between 18 kg/sqm to 38 kg/sqm (extremes included);
Spontaneous amenorrhea for ≥12 consecutive months; or 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 (with or without hysterectomy);
At least 50 moderate to severe vasomotor symptoms per week (ie, 7 consecutive days), as recorded in the daily diary during the screening period;
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, as judged by the Investigator;

Key exclusion criteria (17 listed)

Use of a prohibited therapy (hormone therapy, hormonal contraceptive, or vasomotor symptom medication [prescription, over the counter, or herbal]) or not willing to wash out drugs
History (in the past year) or presence of drug or alcohol abuse;
Previous or current history of a malignant tumor, except for basal cell carcinoma;
Uncontrolled hypertension and a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg;
Judged by the Investigator to be unsuited to participate in the study based on findings observed during physical examination, vital sign assessment, or 12-lead electrocardiogram (ECG);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FezolinetantAlso: ESN364Oral Capsule	Drug	Fezolinetant 120 mg + Placebo, Fezolinetant 30 mg, Fezolinetant 30 mg + Placebo, Fezolinetant 60 mg, Fezolinetant 60 mg + Placebo, Fezolinetant 90 mg, Placebo
PlaceboOral Capsule	Drug	Fezolinetant 15 mg

Primary outcome

Co-Primary Efficacy Endpoint: Change From Baseline (CFB) in The Mean Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Week 4
Time frame: Baseline and week 4
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12
Time frame: Baseline and week 12
The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity 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 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).
Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4
Time frame: Baseline and week 4
Severity of moderate to severe VMS per day was calculated as follows: [(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 moderate or severe VMS. Higher score indicates greater severity.
Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12
Time frame: Baseline and week 12
Severity of moderate to severe VMS per day was calculated as follows: [(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS. Moderate VMS was defined as sensation of heat with sweating/dampness, but 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 moderate or severe VMS. Higher scores indicates greater severity.

32 secondary outcomes

Change From Baseline in The Mean Frequency of Mild, Moderate, and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Mean Frequency of Moderate and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15
Change From Baseline in The Mean Severity of Mild, Moderate, and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Mean Severity of Moderate and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15
Change From Baseline in The Hot Flash Score of Mild, Moderate, and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in The Hot Flash Score of Moderate and Severe VMS to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Mean Percent Reduction of Mild, Moderate, And Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Mean Percent Reduction of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 50% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
Number of Participants With Mean Percent Reduction of 70% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 90% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Mild, Moderate, and Severe VMS From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 50% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 70% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 90% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate and Severe Vasomotor Symptoms From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 2 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 3 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 4 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 5 in Mean Number of Mild, Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 2 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 3 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 4 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Absolute Reduction of 5 in Mean Number of Moderate and Severe VMS Per Day From Baseline to Each Study Week
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Change From Baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) at Weeks 4, 8, 12, and 15
Time frame: Baseline and weeks 4, 8, 12, and 15
Leeds Sleep Evaluation Questionnaire (LSEQ) Domain Scores at Weeks 4, 8, 12 and 15
Time frame: Weeks 4, 8, 12, and 15
Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8, 12, and 15
Time frame: Baseline and weeks 4, 8, 12, and 15
Change From Baseline in Menopause-Specific Quality of Life (MENQoL) at Weeks 4, 8, 12, and 15
Time frame: Baseline and weeks 4, 8, 12, and 15
Change Over Time From Baseline in Plasma Concentrations of Luteinizing Hormone (LH) at Week 12
Time frame: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Follicle-Stimulating Hormone (FSH) at Week 12
Time frame: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Estradiol (E2) at Week 12
Time frame: Baseline and week 12
Change Over Time From Baseline in Plasma Concentrations of Sex Hormone-Binding Globulin (SHBG) at Week 12
Time frame: Baseline and week 12

Results and safety

Results posted to the registry on 29 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo BID	44	37
Fezolinetant 15 mg BID	45	40
Fezolinetant 30 mg BID	44	38
Fezolinetant 60 mg BID	45	33
Fezolinetant 90 mg BID	44	32
Fezolinetant 30 mg QD	45	34
Fezolinetant 60 mg QD	45	36
Fezolinetant 120 mg QD	44	37

Primary outcome: Co-Primary Efficacy Endpoint: Change From Baseline (CFB) in The Mean Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Week 4

Time frame: Baseline and week 4. Least squares mean (Standard Error). Unit: VMS per day

Measure	Placebo BID n = 42	Fezolinetant 15 mg BID n = 40	Fezolinetant 30 mg BID n = 41	Fezolinetant 60 mg BID n = 40	Fezolinetant 90 mg BID n = 37	Fezolinetant 30 mg QD n = 40	Fezolinetant 60 mg QD n = 43	Fezolinetant 120 mg QD n = 42
Value	-4.2 (0.65)	-6.1 (0.65)	-7.2 (0.64)	-7.0 (0.62)	-7.7 (0.65)	-6.5 (0.65)	-7.2 (0.61)	-6.6 (0.63)

Placebo BID vs Fezolinetant 15 mg BID: LSMean difference: -1.9 (95% CI -3.56 to -0.25), p = 0.0240, ANCOVA
Placebo BID vs Fezolinetant 30 mg BID: LSMean difference: -3.0 (95% CI -4.68 to -1.38), p = 0.0004, ANCOVA
Placebo BID vs Fezolinetant 60 mg BID: LSMean difference: -2.8 (95% CI -4.44 to -1.14), p = 0.0010, ANCOVA

Population analysed: FAS population with available data at specified time point.

Primary outcome: Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12

Time frame: Baseline and week 12. Least squares mean (Standard Error). Unit: VMS per day

Measure	Placebo n = 37	Fezolinetant 15 mg BID n = 38	Fezolinetant 30 mg BID n = 37	Fezolinetant 60 mg BID n = 31	Fezolinetant 90 mg BID n = 31	Fezolinetant 30 mg QD n = 33	Fezolinetant 60 mg QD n = 36	Fezolinetant 120 mg QD n = 36
Value	-5.3 (0.58)	-7.2 (0.54)	-7.5 (0.56)	-7.6 (0.55)	-8.0 (0.58)	-7.4 (0.58)	-7.9 (0.54)	-7.4 (0.57)

Placebo vs Fezolinetant 15 mg BID: LSMean difference: -1.8 (95% CI -3.30 to -0.35), p = 0.0154, ANCOVA
Placebo vs Fezolinetant 30 mg BID: LSMean difference: -2.1 (95% CI -3.60 to -0.67), p = 0.0043, ANCOVA
Placebo vs Fezolinetant 60 mg BID: LSMean difference: -2.3 (95% CI -3.76 to -0.83), p = 0.0023, ANCOVA

Population analysed: FAS population with available data at specified time point.

Primary outcome: Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4

Time frame: Baseline and week 4. Least squares mean (Standard Error). Unit: Score on a scale

Measure	Placebo n = 42	Fezolinetant 15 mg BID n = 40	Fezolinetant 30 mg BID n = 41	Fezolinetant 60 mg BID n = 40	Fezolinetant 90 mg BID n = 37	Fezolinetant 30 mg QD n = 40	Fezolinetant 60 mg QD n = 43	Fezolinetant 120 mg QD n = 42
Value	-0.3 (0.15)	-0.8 (0.14)	-0.9 (0.15)	-1.2 (0.14)	-1.3 (0.15)	-0.7 (0.15)	-0.9 (0.14)	-1.0 (0.15)

Placebo vs Fezolinetant 15 mg BID: LSMean difference: -0.5 (95% CI -0.84 to -0.07), p = 0.0215, ANCOVA
Placebo vs Fezolinetant 30 mg BID: LSMean difference: -0.6 (95% CI -1.01 to -0.24), p = 0.0017, ANCOVA
Placebo vs Fezolinetant 60 mg BID: LSMean difference: -0.8 (95% CI -1.21 to -0.44), p <0.0001, ANCOVA

Population analysed: FAS population with available data at specified time point.

Primary outcome: Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12

Time frame: Baseline and week 12. Least squares mean (Standard Error). Unit: Score on a scale

Measure	Placebo n = 37	Fezolinetant 15 mg BID n = 38	Fezolinetant 30 mg BID n = 37	Fezolinetant 60 mg BID n = 31	Fezolinetant 90 mg BID n = 31	Fezolinetant 30 mg QD n = 33	Fezolinetant 60 mg QD n = 36	Fezolinetant 120 mg QD n = 36
Value	-0.8 (0.16)	-1.0 (0.15)	-1.1 (0.16)	-1.3 (0.16)	-1.4 (0.17)	-0.9 (0.16)	-1.3 (0.15)	-1.1 (0.16)

Placebo vs Fezolinetant 15 mg BID: LSMean difference: -0.3 (95% CI -0.67 to -0.16), p = 0.2324, ANCOVA
Placebo vs Fezolinetant 30 mg BID: LSMean difference: -0.4 (95% CI -0.80 to 0.04), p = 0.0736, ANCOVA
Placebo vs Fezolinetant 60 mg BID: LSMean difference: -0.6 (95% CI -0.98 to -0.15), p = 0.0080, ANCOVA

Population analysed: FAS population with available data at specified time point.

32 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of informed consent until end of the study (up to 15 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo BID	0 of 43 (0%)	5 of 43 (11.6%)	0 of 43
Fezolinetant 15 mg BID	0 of 45 (0%)	9 of 45 (20%)	0 of 45
Fezolinetant 30 mg BID	0 of 43 (0%)	7 of 43 (16.3%)	0 of 43
Fezolinetant 60 mg BID	0 of 45 (0%)	11 of 45 (24.4%)	0 of 45
Fezolinetant 90 mg BID	0 of 44 (0%)	11 of 44 (25%)	0 of 44
Fezolinetant 30 mg QD	0 of 43 (0%)	12 of 43 (27.9%)	0 of 43
Fezolinetant 60 mg QD	1 of 45 (2.2%)	14 of 45 (31.1%)	0 of 45
Fezolinetant 120 mg QD	0 of 44 (0%)	11 of 44 (25%)	0 of 44

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32102086Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N, Lee M, Skillern L, Ramael S. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020 Apr;27(4):382-392. doi: 10.1097/GME.0000000000001510.
Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Related trials for Menopause

Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruiting
The Role of Diet Quality in Sleep Among Women in Postmenopause
Post Menopausal Women
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruiting
Effect of Hormone Replacement Therapy on Physiotherapy Outcomes in Postmenopausal Women With Frozen Shoulder
Frozen Shoulder, Adhesive Capsulitis
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Astellas Pharma Global Development, Inc.

51 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fezolinetant in people with Menopause and Hot Flashes, run by Astellas Pharma Global Development, Inc. at 51 sites in United States.

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 13 inclusion and 17 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 26 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 51 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 29 Sep 2021). 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?

Co-Primary Efficacy Endpoint: Change From Baseline (CFB) in The Mean Frequency of Moderate to Severe Vasomotor Symptoms (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 NCT03192176, which also lists 1 linked publication.

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 26 Nov 2024.