NCT04003142: Skylight 2

A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause - 2

Completed Phase 3 Results posted Last updated 5 November 2024

What this trial tests

Phase 3 trial testing Fezolinetant in Hot Flashes in 501 participants. Completed in 23 April 2021.

Timeline

10 July 2019

Primary endpoint
30 July 2020

23 April 2021

Quick facts

Lead sponsor	Astellas Pharma Global Development, Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	501
Start date	10 July 2019
Primary completion	30 July 2020
Estimated completion	23 April 2021
Sites	93 locations across United Kingdom, Poland, Canada, Czechia, United States, Spain, Latvia

Drugs / interventions tested

• Fezolinetant (FEZOLINETANT) — full drug profile →
• placebo

Conditions studied

• Hot Flashes — all drugs for Hot Flashes →

Sponsor

Astellas Pharma Global Development, Inc. — full company profile →

Who can join

Adults 40 to 65, female only, with Hot Flashes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4 Primary · 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 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 ta

Group	Value	95% CI
Double-blind Period: Placebo	-3.72	± 0.33
Double-blind Period: Fezolinetant 30 mg	-5.53	± 0.33
Double-blind Period: Fezolinetant 45 mg	-6.26	± 0.33

Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12 Primary · 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 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 ta

Group	Value	95% CI
Double-blind Period: Placebo	-4.97	± 0.39
Double-blind Period: Fezolinetant 30 mg	-6.83	± 0.39
Double-blind Period: Fezolinetant 45 mg	-7.50	± 0.39

Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4 Primary · Baseline and 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 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 swe

Group	Value	95% CI
Double-blind Period: Placebo	-0.32	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.47	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.61	± 0.05

Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12 Primary · Baseline and 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 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 swe

Group	Value	95% CI
Double-blind Period: Placebo	-0.48	± 0.06
Double-blind Period: Fezolinetant 30 mg	-0.64	± 0.06
Double-blind Period: Fezolinetant 45 mg	-0.77	± 0.06

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 Secondary · Baseline and 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 participants 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 dist

Group	Value	95% CI
Double-blind Period: Placebo	-3.4	± 0.5
Double-blind Period: Fezolinetant 30 mg	-4.1	± 0.5
Double-blind Period: Fezolinetant 45 mg	-5.5	± 0.5

Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Secondary · Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, and 11

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 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 ta

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-2.32	± 0.28
Double-blind Period: Fezolinetant 30 mg	-3.62	± 0.29
Double-blind Period: Fezolinetant 45 mg	-4.03	± 0.29

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-3.06	± 0.32
Double-blind Period: Fezolinetant 30 mg	-4.82	± 0.32
Double-blind Period: Fezolinetant 45 mg	-5.03	± 0.32

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-3.56	± 0.32
Double-blind Period: Fezolinetant 30 mg	-5.29	± 0.32
Double-blind Period: Fezolinetant 45 mg	-5.95	± 0.32

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-4.05	± 0.34
Double-blind Period: Fezolinetant 30 mg	-5.89	± 0.34
Double-blind Period: Fezolinetant 45 mg	-6.71	± 0.34

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-4.25	± 0.33
Double-blind Period: Fezolinetant 30 mg	-6.03	± 0.33
Double-blind Period: Fezolinetant 45 mg	-6.91	± 0.33

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-4.44	± 0.35
Double-blind Period: Fezolinetant 30 mg	-6.24	± 0.35
Double-blind Period: Fezolinetant 45 mg	-6.78	± 0.35

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-4.48	± 0.37
Double-blind Period: Fezolinetant 30 mg	-6.25	± 0.37
Double-blind Period: Fezolinetant 45 mg	-6.86	± 0.37

Week 9

Group	Value	95% CI
Double-blind Period: Placebo	-4.88	± 0.38
Double-blind Period: Fezolinetant 30 mg	-6.54	± 0.38
Double-blind Period: Fezolinetant 45 mg	-7.39	± 0.38

Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Secondary · Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11

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 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 swe

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-0.18	± 0.03
Double-blind Period: Fezolinetant 30 mg	-0.32	± 0.03
Double-blind Period: Fezolinetant 45 mg	-0.34	± 0.03

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-0.24	± 0.04
Double-blind Period: Fezolinetant 30 mg	-0.41	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.42	± 0.04

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-0.31	± 0.04
Double-blind Period: Fezolinetant 30 mg	-0.42	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.54	± 0.04

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-0.37	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.53	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.66	± 0.05

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-0.37	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.55	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.65	± 0.05

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-0.42	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.58	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.70	± 0.05

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-0.43	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.56	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.69	± 0.05

Week 9

Group	Value	95% CI
Double-blind Period: Placebo	-0.46	± 0.06
Double-blind Period: Fezolinetant 30 mg	-0.59	± 0.06
Double-blind Period: Fezolinetant 45 mg	-0.74	± 0.06

Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Secondary · Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 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 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 ta

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-20.82	± 2.42
Double-blind Period: Fezolinetant 30 mg	-32.98	± 2.43
Double-blind Period: Fezolinetant 45 mg	-36.50	± 2.45

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-29.21	± 2.69
Double-blind Period: Fezolinetant 30 mg	-43.82	± 2.69
Double-blind Period: Fezolinetant 45 mg	-45.16	± 2.71

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-33.17	± 2.76
Double-blind Period: Fezolinetant 30 mg	-48.68	± 2.75
Double-blind Period: Fezolinetant 45 mg	-53.42	± 2.76

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	-34.72	± 2.78
Double-blind Period: Fezolinetant 30 mg	-51.06	± 2.77
Double-blind Period: Fezolinetant 45 mg	-56.37	± 2.77

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-37.88	± 2.75
Double-blind Period: Fezolinetant 30 mg	-53.50	± 2.75
Double-blind Period: Fezolinetant 45 mg	-60.76	± 2.74

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-39.64	± 2.73
Double-blind Period: Fezolinetant 30 mg	-54.42	± 2.73
Double-blind Period: Fezolinetant 45 mg	-62.30	± 2.73

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-40.91	± 2.84
Double-blind Period: Fezolinetant 30 mg	-55.88	± 2.84
Double-blind Period: Fezolinetant 45 mg	-62.38	± 2.83

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-41.84	± 2.86
Double-blind Period: Fezolinetant 30 mg	-56.22	± 2.86
Double-blind Period: Fezolinetant 45 mg	-62.42	± 2.84

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 Secondary · Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 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 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 ta

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	28
Double-blind Period: Fezolinetant 30 mg	46
Double-blind Period: Fezolinetant 45 mg	58

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	39
Double-blind Period: Fezolinetant 30 mg	71
Double-blind Period: Fezolinetant 45 mg	71

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	48
Double-blind Period: Fezolinetant 30 mg	81
Double-blind Period: Fezolinetant 45 mg	89

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	44
Double-blind Period: Fezolinetant 30 mg	84
Double-blind Period: Fezolinetant 45 mg	88

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	54
Double-blind Period: Fezolinetant 30 mg	84
Double-blind Period: Fezolinetant 45 mg	98

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	53
Double-blind Period: Fezolinetant 30 mg	81
Double-blind Period: Fezolinetant 45 mg	95

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	55
Double-blind Period: Fezolinetant 30 mg	84
Double-blind Period: Fezolinetant 45 mg	92

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	56
Double-blind Period: Fezolinetant 30 mg	81
Double-blind Period: Fezolinetant 45 mg	103

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 Secondary · Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 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 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 ta

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	1
Double-blind Period: Fezolinetant 30 mg	1
Double-blind Period: Fezolinetant 45 mg	3

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	3
Double-blind Period: Fezolinetant 30 mg	8
Double-blind Period: Fezolinetant 45 mg	4

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	5
Double-blind Period: Fezolinetant 30 mg	4
Double-blind Period: Fezolinetant 45 mg	11

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	3
Double-blind Period: Fezolinetant 30 mg	10
Double-blind Period: Fezolinetant 45 mg	17

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	3
Double-blind Period: Fezolinetant 30 mg	12
Double-blind Period: Fezolinetant 45 mg	11

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	9
Double-blind Period: Fezolinetant 30 mg	12
Double-blind Period: Fezolinetant 45 mg	17

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	9
Double-blind Period: Fezolinetant 30 mg	13
Double-blind Period: Fezolinetant 45 mg	18

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	10
Double-blind Period: Fezolinetant 30 mg	17
Double-blind Period: Fezolinetant 45 mg	22

Change From Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24 Secondary · Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

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 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 ta

Group	Value	95% CI
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	-7.86	± 4.21
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	-7.96	± 4.53
Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg	-9.01	± 5.80
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	-7.08	± 5.40

Change From Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24 Secondary · Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

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 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 swe

Group	Value	95% CI
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	-0.85	± 0.88
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	-0.90	± 0.80
Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg	-0.78	± 0.85
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	-0.95	± 0.88

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose date up to 21 days after last dose (up to 55 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-blind Period: Placebo

Serious: 0/167 (0%)

Deaths: 0/167

Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg

Serious: 9/166 (5%)

Deaths: 0/166

Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg

Serious: 8/167 (5%)

Deaths: 0/167

Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg

Serious: 2/76 (3%)

Deaths: 0/76

Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg

Serious: 4/75 (5%)

Deaths: 1/75

Serious adverse events (22 terms)

Reaction	System	Double-blind Period: Placebo	Double-blind Period: Fezol…	Double-blind Period: Fezol…	Double-blind Period: Place…	Double-blind Period: Place…
COVID-19	Infections and infestations	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—
Biliary dyskinesia	Hepatobiliary disorders	—	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—	—
Hepatotoxicity	Hepatobiliary disorders	—	—	—	—	—
Tooth infection	Infections and infestations	—	—	—	—	—
Foot fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Limb injury	Injury, poisoning and procedural complications	—	—	—	—	—
Limb traumatic amputation	Injury, poisoning and procedural complications	—	—	—	—	—
Multiple injuries	Injury, poisoning and procedural complications	—	—	—	—	—
Posterior tibial nerve injury	Injury, poisoning and procedural complications	—	—	—	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—	—	—	—
Tendonitis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Invasive breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Postmenopausal haemorrhage	Reproductive system and breast disorders	—	—	—	—	—
Vaginal haemorrhage	Reproductive system and breast disorders	—	—	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Double-blind Period: Placebo	Double-blind Period: Fezol…	Double-blind Period: Fezol…	Double-blind Period: Place…	Double-blind Period: Place…
COVID-19	Infections and infestations	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Hot flush	Vascular disorders	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—

Most-reported serious reactions: COVID-19, Atrial fibrillation, Coronary artery disease, Chest pain, Non-cardiac chest pain, Biliary dyskinesia, Cholecystitis acute, Hepatotoxicity.

Data from ClinicalTrials.gov NCT04003142 adverse events section.

Sponsor's own description

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 are fezolinetant 30 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 is a dummy treatment that looks like medicine but does not have 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 is 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 shows 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 is like flipping a coin.

The study participants took study treatment for 52 weeks. The first 12 weeks of study treatment was "double-blinded." That means that the study participants and the study doctors did not know who took which of the study treatments (fezolinetant 30 mg, fezolinetant 45 mg or placebo) during that time. The last 40 weeks of study treatment was "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 went to the hospital or clinic for a check-up. They were asked about medications, side effects and how they felt. Other checks included physical exam and vital signs (heart rate, temperature and blood pressure). Blood and urine was collected for laboratory tests. Study participants completed questionnaires that were about how hot flashes affect their daily life. Study participants who 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 involved removing a small amount of tissue from the inside lining of the uterus. The tissue was then checked under a microscope. The other test was transvaginal ultrasound. This test used sound waves to create pictures of the organs in the pelvis. The sound waves are transmitted by a probe (transducer), which was placed inside the vagina. Study participants might 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 have this test done in the last 12 months had it done at the first study visit. They had done at the last study visit if they were due for their screening mammogram and their own doctor agrees.

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
   Johnson KA, Martin N, Nappi RE, Neal-Perry G, et al · · 2023 · cited 117× · PMID 36734148 · DOI 10.1210/clinem/dgad058
2. Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause: A Randomized Controlled Trial.
   Neal-Perry G, Cano A, Lederman S, Nappi RE, et al · · 2023 · cited 73× · PMID 36897180 · DOI 10.1097/aog.0000000000005114
3. Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).
   Santoro N, Nappi RE, Neal-Perry G, English M, et al · · 2024 · cited 11× · PMID 38517210 · DOI 10.1097/gme.0000000000002340
4. Psychometric Evaluation of the MENQOL Instrument in Women Experiencing Vasomotor Symptoms Associated with Menopause.
   Schultz NM, Morga A, Siddiqui E, Rhoten SE. · · 2024 · cited 8× · PMID 38396203 · DOI 10.1007/s12325-024-02787-z
5. Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis.
   Rahman UA, Kashif TB, Usman M, Rana M, et al · · 2023 · cited 7× · PMID 38115258 · DOI 10.1097/md.0000000000036592
6. Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies.
   Kagan R, Cano A, Nappi RE, English ML, et al · · 2025 · cited 6× · PMID 39739195 · DOI 10.1007/s12325-024-03073-8
7. In Vitro Evaluation of CYP-Mediated Metabolism of Fezolinetant and Pharmacokinetic Interaction Between Fezolinetant and Fluvoxamine in Healthy Postmenopausal Smokers and Nonsmokers.
   Iwai M, Nielsen J, Miyagawa M, Patton M, et al · · 2025 · cited 6× · PMID 39558800 · DOI 10.1002/jcph.6157
8. Psychometric evaluation of the PROMIS SD-SF-8b instrument in individuals experiencing vasomotor symptoms due to menopause.
   Schultz NM, Morga A, Siddiqui E, Rhoten SE. · · 2023 · cited 5× · PMID 37990323 · DOI 10.1186/s12955-023-02206-x