Phase 3 N=501 Randomized Double-blind Treatment

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

Hot Flashes

Bottom Line

View on ClinicalTrials.gov: NCT04003142 ↗

Enrolled (actual)

501

Serious AEs

3.5%

Results posted

Jun 2022

Primary outcome: Primary: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4 — -3.72; -5.53; -6.26 VMS per day — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Fezolinetant (Drug); placebo (Drug)
Age: Adult, Older Adult · 40+ yrs
Sex: Female
Sponsor: Astellas Pharma Global Development, Inc.
Primary completion: Jul 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4	-3.72; -5.53; -6.26	<0.001 sig
PRIMARY Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12	-4.97; -6.83; -7.50	<0.001 sig
PRIMARY Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4	-0.32; -0.47; -0.61	0.021 sig
PRIMARY Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12	-0.48; -0.64; -0.77	0.049 sig
SECONDARY 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	-3.4; -4.1; -5.5	0.381
SECONDARY Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12	-2.32; -3.62; -4.03; -3.06; -4.82; -5.03	0.001 sig
SECONDARY Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12	-0.18; -0.32; -0.34; -0.24; -0.41; -0.42	0.001 sig
SECONDARY Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12	-20.82; -32.98; -36.50; -29.21; -43.82; -45.16	<0.001 sig
SECONDARY 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	28; 46; 58; 39; 71; 71	0.020 sig
SECONDARY 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	1; 1; 3; 3; 8; 4	0.951
SECONDARY Change From Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24	-7.86; -7.96; -9.01; -7.08	—
SECONDARY Change From Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24	-0.85; -0.90; -0.78; -0.95	—
SECONDARY Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit	25; 61; 68; 2; 23; 21	—
SECONDARY Number of Participants With Adverse Events	54; 107; 106; 43; 45; 11	—

Summary

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.

Eligibility Criteria

Inclusion Criteria

Subject has a body mass index ≥ 18 kg/m^2 and ≤ 38 kg/m^2.
Subject must be seeking treatment or relief for vasomotor symptoms (VMS) associated with menopause and confirmed as menopausal per 1 of the following criteria at the screening visit:
Spontaneous amenorrhea for ≥ 12 consecutive months
Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L); or
Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
Within the 10 days prior to randomization, subject must have a minimum average of 7 to 8 moderate to severe hot flashes (HFs) vasomotor symptoms (VMS) per day, or 50 to 60 per week.
Subject is in good general health as determined on the basis of medical history and general physical examination, including a bimanual clinical pelvic examination and clinical breast examination devoid of relevant clinical findings, performed at the screening visit; hematology and biochemistry parameters, pulse rate and/or blood pressure and electrocardiogram (ECG) within the reference range for the population studied, or showing no clinically relevant deviations.
Subject has documentation of a normal/negative or no clinically significant findings mammogram (obtained at screening or within the prior 12 months of study enrollment). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic findings.
Subject is willing to undergo a transvaginal ultrasound (TVU) to evaluate the uterus and ovaries at screening and at week 52 end of treatment (EOT), and for subjects who are withdrawn from the study prior to completion, a TVU at the early discontinuation (ED) visit.
Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT), for subjects with uterine bleeding, and for subjects who are withdrawn from the study prior to completion. The endometrial biopsy obtained at screening must be considered evaluable.
Subject has documentation of a normal or not clinically significant Papanicolaou (Pap) test (or equivalent cervical cytology) within the previous 12 months or at screening.
Subject has a negative urine pregnancy test at screening.
Subject has a negative serology panel (i.e. negative hepatitis B surface antigen, negative hepatitis C virus antibody and negative human immunodeficiency virus antibody screens) at screening.
Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria

Subject uses a prohibited therapy (strong or moderate cytochrome P450 1A2 [CYP1A2] inhibitors, hormone replacement therapy [HRT], hormonal contraceptive or any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue use of such drugs for the full duration of study conduct.
Subject has known substance abuse or alcohol addiction within 6 months of screening.
Subject has previous or current history of a malignant tumor, except for basal cell carcinoma.
Subject's systolic blood pressure is ≥ 130 mmHg or diastolic blood pressure is ≥ 80 mmHg based on the average of 2 to 3 readings, on at least 2 different occasions within the screening period.
Subjects who do not meet these criteria may be re-assessed after initiation or review of antihypertensive measures.
Subjects with a medical history of hypertension can be enrolled once they are medically clear (stable and compliant).
Subject has history of severe allergy, hypersensitivity or intolerance to drugs in general, including the study drug and any of its excipients.
Subject has an unacceptable result from the TVU assessment at screening (i.e., full length of endometrial cavity cannot be visualized or presence of a clinically significant finding).
Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyp

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Data sourced from ClinicalTrials.gov (NCT04003142). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.