Fezolinetant and Vascular Health and Brain Health

NCT07606664 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STUDY25120039
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn whether a study drug called fezolinetant impacts cardiovascular and cognitive health in women who have moderate to severe menopausal hot flashes and night sweats. Researchers will compare fezolinetant to a placebo. A placebo is a pill that looks like the study drug but does not contain any active medicine. This comparison helps researchers understand whether fezolinetant works better than no treatment. Participants will: Be randomly assigned to take either fezolinetant (45 mg) or a placebo once a day for 12 weeks. Visit the research clinic for regular checkups and tests during the study. Complete tests that measure blood vessel function and cognition. Participants and study staff will not know which treatment each participant receives during the study.

Conditions

Menopause Hot Flashes

Keywords

menopause; hot flashes; vascular health; brain health; women's health; cognition

Outcome Measures

Primary Outcomes (2)

• Flow-Mediated Dilation

  Endothelial function assessed by flow-mediated dilation

  Baseline and end of treatment at 12 weeks.

• Verbal Memory Performance

  Verbal memory neuropsychological test performance

  Baseline and end of treatment at 12 weeks.

Secondary Outcomes (6)

• Endothelial Biomarkers

  Baseline and end of treatment at 12 weeks.

• Brain Activation during Verbal Encoding

  Baseline and end of treatment at 12 weeks.

• Functional Connectivity during recall

  Baseline and end of treatment at 12 weeks.

• Subjective Vasomotor Hot Flash Diary

  Baseline and end of treatment at 12 weeks.

• Objective Vasomotor Monitoring

  Baseline and end of treatment at 12 weeks.

Study Arms (2)

Placebo Arm

PLACEBO COMPARATOR

The placebo tablet will be an identical tablet appearing to active medication. The placebo tablets contain the following inactive ingredients: ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Drug: Placebo

Active Study Drug

EXPERIMENTAL

Fezolinetant is a white powder. It is very slightly soluble in water (0.29 mg/mL). Fezolinetant tablets that will be used in this study are round, light red film-coated tablets with no marking on the tablets. Each fezolinetant tablet for oral use contains 45 mg of fezolinetant and the following inactive ingredients: ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Drug: Fezolinetant

Interventions

Placebo DRUG

The placebo tablet will be an identical tablet appearing to active medication. The placebo tablets contain the following inactive ingredients: ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide).

Placebo Arm

Fezolinetant DRUG

Fezolinetant is a white powder. It is very slightly soluble in water (0.29 mg/mL). Fezolinetant tablets that will be used in this study are round, light red film-coated tablets with no marking on the tablets. Each fezolinetant tablet for oral use contains 45 mg of fezolinetant and the following inactive ingredients: ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Active Study Drug

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Born female
• Age ≥40 - ≤65 years at the time of the screening visit
• Body Mass Index (BMI) ≥18 to ≤38 kg/m2
• Seeking treatment or relief for moderate to severe VMS associated with menopause
• Confirmed menopausal as per one of the following criteria at the time of screening: Reporting spontaneous amenorrhea for ≥12 consecutive months; spontaneous amenorrhea for ≥6 and \< 12 months with follicle-stimulating hormone \>40 IU/L
• Negative urine pregnancy test at screening (if \<12 months of amenorrhea)
• A minimum average of 7-8 moderate to severe VMS per day, or 50-60 per week prior to randomization as reported in the 7-day hot flash diary
• Agrees to not participate in another interventional study (pharmaceutical or device) while participating in this current study

You may not qualify if:

• Pregnancy/lactation (past 6 months)
• Any treatment for hot flashes with demonstrated efficacy for hot flashes
• Currently using systemic sex-hormone medications.
• Currently using cytochrome P450 1A2 (CYP1A2) inhibitors (as listed according to the FDA).
• Severely elevated blood pressure \[systolic blood pressure (SBP) \>180 and/or diastolic blood pressure (DBP) \>110\]
• A medical condition or chronic disease (including history of hepatic, renal, cardiovascular, gastrointestinal, pulmonary \[e.g., moderate asthma\], endocrine or gynecological disease) or malignancy that could confound interpretation of the study in the opinion of the investigator or study physician
• Self-reported narcolepsy
• Previous/current history of a malignant tumor, except for basal cell carcinoma
• Participants with known cirrhosis, active liver disease, jaundice, or elevated liver aminotransferases or total bilirubin (ALT, AST, and total bilirubin), should not be enrolled if ALT or AST is ≥ 2 x ULN or if the total bilirubin is ≥ 2 x ULN for the evaluating laboratory. Participants with ALP \> 1.5 × ULN and judged clinically significant by the study physician.
• Severe renal impairment \[estimated glomerular filtration rate (eGFR) 15 to \<30 mL/min per 1.73 m2\] or end-stage renal disease (ESRD) (eGFR \< 15 mL/min/1.73 m2) at screening as per USPI
• Positive Hepatitis C virus antibody, Hepatitis B surface antigen, and/or human immunodeficiency virus antibody screen at screening
• History within the last 6 months of undiagnosed uterine bleeding
• Key medical conditions (history of cardiovascular disease, stroke/cerebrovascular accident, brain injury with loss of consciousness for more than 60 seconds within the last five years, cognitive disorders, brain tumor, dementia, Parkinson's disease, chemotherapy, psychotic disorders)
• Metal in the body, claustrophobia, or cannot undergo 3T magnetic resonance imaging (MRI); Inability to meet MRI eligibility criteria
• Lymph node removal on both sides of the body, mastectomy, or dialysis

Sponsors & Collaborators

• Rebecca Thurston: lead
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (2)

University of Illinois, Chicago

Chicago, Illinois, 60612, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

MeSH Terms

Conditions

Hot Flashes

Interventions

fezolinetant

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Rebecca C Thurston, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah M Conklin, PhD

CONTACT

878-261-6899; conklinsm2@upmc.edu

Mollie B Bandy, BA

CONTACT

412-648-9088; BandyMB@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Dean for Women's Health Research; Distinguished Professor of Psychiatry, Psychology, Epidemiology, and Clinical and Translational Sciences

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 26, 2026
• Study Start (Estimated): September 25, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)