Evidence mapPaperPMID 39739195Full record

SynthesisAdvances in therapy2025

Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies.

Risa Kagan, Antonio Cano, Rossella E Nappi, Marci L English, Shayna Mancuso, Xi Wu, Faith D Ottery

3 registry-linked trialsAbstract readMeta-Analysis
In one paragraph

Synthesis in Advances in therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04003142 phase3completednot on this map

A Phase 3, Randomized, Placebo-controlled, 12-week Double-blind Study, Followed by a Non-Controlled Extension Treatment Period, to Assess the Efficacy and Safety of Fezolinetant in Women Suffering From Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated With Menopause

TypeinterventionalSponsorAstellas Pharma Global Development, Inc.Ran2019 to 2021Enrolled501ConditionsHot FlashesArmsFezolinetant, placebo
NCT04003155 phase3completednot on this map

A Phase 3, Randomized, Placebo-controlled, 12-week Double-blind Study, Followed by a Non-Controlled Extension Treatment Period, to Assess the Efficacy and Safety of Fezolinetant in Women Suffering From Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated With Menopause

TypeinterventionalSponsorAstellas Pharma Global Development, Inc.Ran2019 to 2021Enrolled527ConditionsHot FlashesArmsfezolinetant, placebo
NCT04003389 phase3completednot on this map

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

TypeinterventionalSponsorAstellas Pharma Global Development, Inc.Ran2019 to 2022Enrolled1,831ConditionsHot FlashesArmsfezolinetant, placebo
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Risa KaganObstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA and Sutter East Bay Medical Foundation, 2500 Milvia Street, Berkeley, CA, 94704, USA. risa.kagan@sutterhealth.org.ORCID http://orcid.org/0000-0002-6826-0787
Antonio CanoUniversity of Valencia, Valencia, Spain.ORCID http://orcid.org/0000-0001-8046-0303
Rossella E NappiUniversity of Pavia, Pavia, Italy.ORCID http://orcid.org/0000-0003-1713-6396
Marci L EnglishAstellas Pharma Global Development, Northbrook, IL, USA.
Shayna MancusoAstellas Pharma Global Development, Northbrook, IL, USA.
Xi WuAstellas Pharma Global Development, Northbrook, IL, USA.
Faith D OtteryAstellas Pharma Global Development, Northbrook, IL, USA.ORCID http://orcid.org/0000-0002-6295-5166

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThis study evaluated the safety and tolerability of fezolinetant in women with vasomotor symptoms (VMS) due to menopause in a pooled analysis of data from three 52-week phase 3 studies (SKYLIGHT 1, 2, and 4).

methodsSKYLIGHT 1 and 2 were double-blind, placebo-controlled studies where women (≥ 40 to ≤ 65 years), with moderate to severe VMS (minimum average ≥ 7 hot flashes/day) were randomized to once-daily placebo, fezolinetant 30 mg or 45 mg. After 12 weeks, those on placebo were re-randomized to fezolinetant 30 mg or 45 mg, while those on fezolinetant continued on their assigned dose for 40 weeks. SKYLIGHT 4 was a placebo-controlled, double-blind, 52-week safety study. Safety was assessed by frequency of treatment-emergent adverse events (TEAEs) and endometrial events. TEAEs of special interest included liver test elevations and endometrial hyperplasia or cancer or disordered proliferative endometrium.

resultsTotals of 952 participants receiving placebo, 1100 receiving fezolinetant 45 mg, and 1103 receiving fezolinetant 30 mg took ≥ 1 dose of study medication. TEAEs occurred in 55.3%, 62.9%, and 65.4%, respectively; exposure-adjusted results were consistent with these results. Most frequent TEAEs in fezolinetant-treated participants included upper respiratory tract infection (7.7-8.3%), headache (6.8-8.2%), coronavirus disease 2019 (5.8-6.1%), back pain (3.1-3.7%), arthralgia (2.9-3.2%), diarrhea (2.3-3.2%), urinary tract infection (2.9-3.4%), and insomnia (2.0-3.0%). The incidence of drug-related serious TEAEs and associated treatment withdrawals was low. Elevations in liver transaminases occurred in 1.5-2.3% of fezolinetant-treated participants, were typically asymptomatic and transient, resolved on treatment or discontinuation, with no evidence of severe drug-induced liver injury (Hy's law). Endometrial safety results were well within US Food and Drug Administration criteria. Analysis of benign and non-benign neoplasm controlled for exposure demonstrated no increased risk versus placebo.

conclusionPooled data confirm the safety and tolerability of fezolinetant over 52 weeks.

trial registrationClinicalTrials.gov identifiers, NCT04003155, NCT04003142, and NCT04003389. Graphical abstract available for this article.

Indexed as

Hot FlashesMenopauseAdultAgedClinical Trials, Phase III as TopicDouble-Blind MethodEstradiolFemaleHumansMiddle AgedProgesteroneRandomized Controlled Trials as TopicEstradiolProgesteroneTX-001HR52-week safetyEndometrial hyperplasiaFezolinetantNeurokinin 3 receptor antagonistTransaminasesTreatment-emergent adverse eventsVasomotor symptoms

Identifiers

PMID39739195
PMCPMC11787274

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.