Menopause Hot Flashes
Conditions
Keywords
menopause, hot flashes, vascular health, brain health, women's health, cognition
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.
Detailed description
Double-blind, placebo-controlled randomized trial to determine whether 12 weeks of 45 mg of fezolinetant, a non-hormonal treatment for hot flashes associated with menopause, improves vascular and brain health in participants with moderate to severe menopausal hot flashes. Participants will be randomized to either 12 weeks of fezolinetant 45 mg or placebo. Primary endpoints include change from baseline in endothelial function and verbal memory.
Interventions
DRUGPlacebo
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).
DRUGFezolinetant
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.
Sponsors
Rebecca Thurston
Astellas Pharma Global Development, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * Hysterectomy; levonorgestrel-releasing intrauterine systems initiated before 12 months of spontaneous amenorrhea (Not exclusionary if placed after 12 months of spontaneous amenorrhea), or history of endometrial ablation will be excluded due to inability to stage menopause; Bilateral oophorectomy if completed prior to 12 months of spontaneous amenorrhea * Cardiovascular medication use. * Prior exposure to fezolinetant or elinzanetant * Current participation in another interventional study or participated in an interventional study or received any investigational drug within 3 months * Illicit substance use reported in the past week or detected by urine toxicology screen. * Subject has any condition, which in the investigator's or study physician's opinion, makes the subject unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-Mediated Dilation | Baseline and end of treatment at 12 weeks. | Endothelial function assessed by flow-mediated dilation |
| Verbal Memory Performance | Baseline and end of treatment at 12 weeks. | Verbal memory performance on the California Verbal Learning Test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Biomarkers | Baseline and end of treatment at 12 weeks. | Blood-based endothelial function biomarkers |
| Brain Activation during Verbal Encoding | Baseline and end of treatment at 12 weeks. | Memory circuitry as measured by changes in brain activation during performance of a functional magnetic resonance imaging (fMRI) task of verbal encoding |
| Functional Connectivity during recall | Baseline and end of treatment at 12 weeks. | Memory circuitry as measured by changes in functional connectivity during performance of a functional magnetic resonance imaging (fMRI) task of verbal recall |
| Subjective Vasomotor Hot Flash Diary | Baseline and end of treatment at 12 weeks. | frequency of subjectively assessed VMS using a digital hot flash diary |
| Objective Vasomotor Monitoring | Baseline and end of treatment at 12 weeks. | Frequency of objectively measured VMS using 24-hour skin conductance monitoring |
| Sleep Monitoring | Baseline and end of treatment at 12 weeks. | Objective sleep monitoring. |
Countries
United States
Contacts
CONTACTSarah M Conklin, PhD
CONTACTMollie B Bandy, BA
PRINCIPAL_INVESTIGATORRebecca C Thurston, PhD
University of Pittsburgh
Outcome results
None listed