NCT04003155: Skylight 1

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

Completed Phase 3 Results posted Last updated 4 November 2024

What this trial tests

Phase 3 trial testing fezolinetant in Hot Flashes in 527 participants. Completed in 11 August 2021.

Timeline

11 July 2019

Primary endpoint
29 October 2020

11 August 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	527
Start date	11 July 2019
Primary completion	29 October 2020
Estimated completion	11 August 2021
Sites	96 locations across United Kingdom, Poland, Hungary, Canada, United States, Spain, Czechia

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Group	Value	95% CI
Double-blind Period: Placebo	-3.32	± 0.29
Double-blind Period: Fezolinetant 30 mg	-5.19	± 0.30
Double-blind Period: Fezolinetant 45 mg	-5.39	± 0.30

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Group	Value	95% CI
Double-blind Period: Placebo	-3.90	± 0.31
Double-blind Period: Fezolinetant 30 mg	-6.28	± 0.32
Double-blind Period: Fezolinetant 45 mg	-6.44	± 0.31

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense h

Group	Value	95% CI
Double-blind Period: Placebo	-0.27	± 0.04
Double-blind Period: Fezolinetant 30 mg	-0.42	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.46	± 0.04

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense h

Group	Value	95% CI
Double-blind Period: Placebo	-0.37	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.60	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.57	± 0.05

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 patients to report objective measures of sleep (e.g., total amount of sleep, time to fall asleep and amount of wakefulness during sleep). Responses to each of the 8 items range from 1 (no disturbe

Group	Value	95% CI
Double-blind Period: Placebo	-3.2	± 0.5
Double-blind Period: Fezolinetant 30 mg	-3.7	± 0.6
Double-blind Period: Fezolinetant 45 mg	-4.2	± 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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-1.82	± 0.26
Double-blind Period: Fezolinetant 30 mg	-3.63	± 0.26
Double-blind Period: Fezolinetant 45 mg	-3.07	± 0.26

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-2.76	± 0.28
Double-blind Period: Fezolinetant 30 mg	-4.73	± 0.28
Double-blind Period: Fezolinetant 45 mg	-4.58	± 0.28

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-3.15	± 0.28
Double-blind Period: Fezolinetant 30 mg	-5.14	± 0.29
Double-blind Period: Fezolinetant 45 mg	-5.25	± 0.29

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-3.49	± 0.28
Double-blind Period: Fezolinetant 30 mg	-5.56	± 0.29
Double-blind Period: Fezolinetant 45 mg	-5.67	± 0.29

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-3.58	± 0.29
Double-blind Period: Fezolinetant 30 mg	-5.70	± 0.30
Double-blind Period: Fezolinetant 45 mg	-5.97	± 0.29

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-3.71	± 0.30
Double-blind Period: Fezolinetant 30 mg	-5.80	± 0.31
Double-blind Period: Fezolinetant 45 mg	-5.97	± 0.30

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-3.71	± 0.30
Double-blind Period: Fezolinetant 30 mg	-6.10	± 0.31
Double-blind Period: Fezolinetant 45 mg	-6.10	± 0.30

Week 9

Group	Value	95% CI
Double-blind Period: Placebo	-4.09	± 0.30
Double-blind Period: Fezolinetant 30 mg	-6.16	± 0.31
Double-blind Period: Fezolinetant 45 mg	-6.24	± 0.30

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense h

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-0.15	± 0.03
Double-blind Period: Fezolinetant 30 mg	-0.25	± 0.03
Double-blind Period: Fezolinetant 45 mg	-0.25	± 0.03

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-0.21	± 0.03
Double-blind Period: Fezolinetant 30 mg	-0.35	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.36	± 0.03

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-0.27	± 0.04
Double-blind Period: Fezolinetant 30 mg	-0.43	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.43	± 0.04

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-0.29	± 0.04
Double-blind Period: Fezolinetant 30 mg	-0.46	± 0.04
Double-blind Period: Fezolinetant 45 mg	-0.46	± 0.04

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-0.30	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.50	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.55	± 0.05

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-0.28	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.52	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.54	± 0.05

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-0.29	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.57	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.53	± 0.05

Week 9

Group	Value	95% CI
Double-blind Period: Placebo	-0.35	± 0.05
Double-blind Period: Fezolinetant 30 mg	-0.62	± 0.05
Double-blind Period: Fezolinetant 45 mg	-0.56	± 0.05

Mean Percent Change in The 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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	-16.63	± 2.31
Double-blind Period: Fezolinetant 30 mg	-32.15	± 2.34
Double-blind Period: Fezolinetant 45 mg	-28.84	± 2.35

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	-25.08	± 2.50
Double-blind Period: Fezolinetant 30 mg	-42.37	± 2.55
Double-blind Period: Fezolinetant 45 mg	-43.37	± 2.54

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	-28.81	± 2.54
Double-blind Period: Fezolinetant 30 mg	-46.94	± 2.59
Double-blind Period: Fezolinetant 45 mg	-50.00	± 2.57

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	-30.59	± 2.67
Double-blind Period: Fezolinetant 30 mg	-47.34	± 2.72
Double-blind Period: Fezolinetant 45 mg	-51.65	± 2.69

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	-32.55	± 2.65
Double-blind Period: Fezolinetant 30 mg	-50.12	± 2.71
Double-blind Period: Fezolinetant 45 mg	-54.33	± 2.67

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	-33.35	± 2.72
Double-blind Period: Fezolinetant 30 mg	-51.74	± 2.78
Double-blind Period: Fezolinetant 45 mg	-57.18	± 2.73

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	-34.85	± 2.86
Double-blind Period: Fezolinetant 30 mg	-53.14	± 2.93
Double-blind Period: Fezolinetant 45 mg	-56.26	± 2.85

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	-35.71	± 2.83
Double-blind Period: Fezolinetant 30 mg	-55.88	± 2.90
Double-blind Period: Fezolinetant 45 mg	-56.89	± 2.83

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	18
Double-blind Period: Fezolinetant 30 mg	47
Double-blind Period: Fezolinetant 45 mg	44

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	37
Double-blind Period: Fezolinetant 30 mg	64
Double-blind Period: Fezolinetant 45 mg	75

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	42
Double-blind Period: Fezolinetant 30 mg	69
Double-blind Period: Fezolinetant 45 mg	89

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	49
Double-blind Period: Fezolinetant 30 mg	77
Double-blind Period: Fezolinetant 45 mg	94

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	47
Double-blind Period: Fezolinetant 30 mg	76
Double-blind Period: Fezolinetant 45 mg	94

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	50
Double-blind Period: Fezolinetant 30 mg	78
Double-blind Period: Fezolinetant 45 mg	96

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	52
Double-blind Period: Fezolinetant 30 mg	79
Double-blind Period: Fezolinetant 45 mg	98

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	52
Double-blind Period: Fezolinetant 30 mg	93
Double-blind Period: Fezolinetant 45 mg	87

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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Week 1

Group	Value	95% CI
Double-blind Period: Placebo	0
Double-blind Period: Fezolinetant 30 mg	0
Double-blind Period: Fezolinetant 45 mg	0

Week 2

Group	Value	95% CI
Double-blind Period: Placebo	1
Double-blind Period: Fezolinetant 30 mg	3
Double-blind Period: Fezolinetant 45 mg	4

Week 3

Group	Value	95% CI
Double-blind Period: Placebo	1
Double-blind Period: Fezolinetant 30 mg	6
Double-blind Period: Fezolinetant 45 mg	5

Week 4

Group	Value	95% CI
Double-blind Period: Placebo	5
Double-blind Period: Fezolinetant 30 mg	6
Double-blind Period: Fezolinetant 45 mg	8

Week 5

Group	Value	95% CI
Double-blind Period: Placebo	2
Double-blind Period: Fezolinetant 30 mg	10
Double-blind Period: Fezolinetant 45 mg	6

Week 6

Group	Value	95% CI
Double-blind Period: Placebo	2
Double-blind Period: Fezolinetant 30 mg	8
Double-blind Period: Fezolinetant 45 mg	10

Week 7

Group	Value	95% CI
Double-blind Period: Placebo	2
Double-blind Period: Fezolinetant 30 mg	13
Double-blind Period: Fezolinetant 45 mg	13

Week 8

Group	Value	95% CI
Double-blind Period: Placebo	2
Double-blind Period: Fezolinetant 30 mg	10
Double-blind Period: Fezolinetant 45 mg	14

Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Secondary · Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 48, 52 of fezolinetant exposure (weeks 16, 24, 28, 32, 36, 40, 44, 48 and 52 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

The PGI is comprised of 2 companion 1-item PRO measures analogous to the Clinical Global Impression (CGI) scales. These measures provide brief, stand-alone global assessments prior to and after initiating a study medication. Patient-perceived change from the initiation of treatment (PGI-C)-VMS is used to evaluate meaningful within-person changes over time in VMS. This measure provides patient-perceived change from the initiation of treatment. The PGI-C VMS asks: "Compared to the beginning of this study, how would you rate your HFs/night sweats now?" Subject ratings range from (1) much better

Week 4: Much better

Group	Value	95% CI
Double-blind Period: Placebo	32
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	50
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	72
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	1

Week 4: Moderately better

Group	Value	95% CI
Double-blind Period: Placebo	21
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	33
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	24
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 4: A little better

Group	Value	95% CI
Double-blind Period: Placebo	44
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	42
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	35
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 4: No change

Group	Value	95% CI
Double-blind Period: Placebo	55
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	23
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	28
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 4: A little worse

Group	Value	95% CI
Double-blind Period: Placebo	1
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	1
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	0
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 4: Moderately worse

Group	Value	95% CI
Double-blind Period: Placebo	1
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	1
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	1
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 4: Much worse

Group	Value	95% CI
Double-blind Period: Placebo	6
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	0
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	0
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	0

Week 12: Much better

Group	Value	95% CI
Double-blind Period: Placebo	35
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	50
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	74
Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg	31
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	44

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/Fezolinetanat 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 participant was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and

Group	Value	95% CI
Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg	-7.15	± 6.02
Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg	-7.32	± 4.58
Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg	-6.89	± 3.67
Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg	-7.32	± 4.53

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: 1/175 (1%)

Deaths: 0/175

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

Serious: 7/174 (4%)

Deaths: 0/174

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

Serious: 8/173 (5%)

Deaths: 0/173

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

Serious: 3/76 (4%)

Deaths: 0/76

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

Serious: 2/76 (3%)

Deaths: 0/76

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…
Chest pain	General disorders	—	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Foot fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Blood pressure increased	Investigations	—	—	—	—	—
Liver function test increased	Investigations	—	—	—	—	—
Transaminases increased	Investigations	—	—	—	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Apocrine breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Benign lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—
Renal colic	Renal and urinary disorders	—	—	—	—	—
Ureteric stenosis	Renal and urinary disorders	—	—	—	—	—
Pelvic pain	Reproductive system and breast disorders	—	—	—	—	—
Uterine haemorrhage	Reproductive system and breast disorders	—	—	—	—	—
Varicose vein	Vascular disorders	—	—	—	—	—

Other adverse events (7 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…
Headache	Nervous system disorders	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Blood glucose increased	Investigations	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—

Most-reported serious reactions: Chest pain, Cholelithiasis, COVID-19 pneumonia, Ankle fracture, Foot fracture, Blood pressure increased, Liver function test increased, Transaminases increased.

Data from ClinicalTrials.gov NCT04003155 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 were fezolinetant 30 milligrams (mg) (1 tablet of fezolinetant and 1 placebo tablet) once a day, fezolinetant 45 mg (2 tablets of fezolinetant) once a day or placebo (2 tablets) once a day. (Placebo was a dummy treatment that looks like medicine but did not had any medicine in it.) The study compared fezolinetant and placebo after 4 and 12 weeks of dosing. The study evaluated if fezolinetant reduces the number of hot flashes. And the study evaluated if fezolinetant reduces the severity of the hot flashes. Women in the study received an electronic handheld device at the first study visit. (It was similar to a smart phone.) Each day of the study, study participants used this to record their hot flashes. Their record for the 10 days before the start of study treatment was checked. They remained in the study if their record shown 7 or 8 moderate to severe hot flashes per day (50 or more per week). Next, they were picked for 1 of the 2 study treatments (fezolinetant or placebo) by chance alone. It was like flipping a coin. The study participants took study treatment for 52 weeks. The first 12 weeks of study treatment are "double-blinded." That means that the study participants and the study doctors did not knew who took which of the study treatments (fezolinetant 30 mg, fezolinetant 45 mg or placebo) during that time. The last 40 weeks of study treatment are "noncontrolled." That means that each study participant and the study doctors knew which study treatment that study participant took during that time. Women who took fezolinetant during the first 12 weeks continued to take the same dose. Women who took placebo during the first 12 weeks took fezolinetant. Their dose was either 30 mg or 45 mg fezolinetant. At weeks 2, 4, 8, 12, 14, 16 and then once a month, the study participants visited the hospital or clinic for a check-up. They were asked about medications, side effects and how they felt. Other checks included physical exam and vital signs (heart rate, temperature and blood pressure). Blood and urine was collected for laboratory tests. Study participants completed questionnaires that were about how hot flashes affect their daily life. Study participants who still had their uterus had the following 2 tests done at the first and last study visits. One of the 2 tests was endometrial biopsy. This test involves removing a small amount of tissue from the inside lining of the uterus. The tissue was then checked under a microscope. The other test is transvaginal ultrasound. This test used sound waves to create pictures of the organs in the pelvis. The sound waves were transmitted by a probe (transducer), which was placed inside the vagina. Study participants may have a screening mammogram done at the first and/or last study visit. A mammogram is an x-ray picture of the breasts used to screen for breast cancer. Study participants who did not had this test done in the last 12 months had it done at the first study visit. They had it done at the last study visit if they are due for their screening mammogram and their own doctor agrees. The last check-up at the hospital or clinic was 3 weeks after the last dose of study treatment.

Publications & conference data

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

1. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study.
   Lederman S, Ottery FD, Cano A, Santoro N, et al · · 2023 · cited 149× · PMID 36924778 · DOI 10.1016/s0140-6736(23)00085-5
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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