Phase 3
N=1,831
A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause
Hot Flashes
Bottom Line
View on ClinicalTrials.gov: NCT04003389 ↗Enrolled (actual)
1,831
Serious AEs
3.1%
Results posted
Feb 2023
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) — 391; 415; 389; 106 participants
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
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
391; 415; 389; 106; 94; 110 | — |
| PRIMARY Number of Participants With Mild, Moderate and Severe TEAE |
180; 215; 195; 191; 185; 171 | — |
| PRIMARY Percentage of Participants With Endometrial Hyperplasia |
0; 0; 0.5 | — |
| PRIMARY Percentage of Participants With Endometrial Cancer |
0; 0.5; 0 | — |
| SECONDARY Change From Baseline in Endometrial Thickness at Week 52 |
-0.17; -0.15; -0.28 | 0.0604 |
| SECONDARY Percentage of Participants With Disordered Proliferative Endometrium |
2.2; 1.4; 0 | — |
| SECONDARY Change From Baseline in Bone Mineral Density (BMD) at Hip at Week 52 |
-0.010; -0.001; -0.009; -0.011; -0.003; -0.008 | 0.029 sig |
| SECONDARY Change From Baseline in Trabecular Bone Score (TBS) at Hip at Week 52 |
-0.078; -0.011; -0.073; -0.085; -0.024; -0.063 | 0.079 |
| SECONDARY Change From Baseline in BMD at Spine at Week 52 |
-0.013; -0.010; -0.014 | 0.497 |
| SECONDARY Change From Baseline in TBS at Spine at Week 52 |
-0.117; -0.084; -0.119 | 0.527 |
| SECONDARY Number of Participants With Suicidal Ideation and/or Behaviour as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) |
2; 2; 4; 0; 0; 1 | — |
| SECONDARY Number of Participants With Self-injurious Behavior Without Suicidal Intent as Assessed by C-SSRS |
0; 1; 0; 1; 0; 0 | — |
Summary
This study was for women in menopause with hot flashes. Menopause, a normal part of aging, was the time of a woman's last period. Hot flashes can interrupt a woman's daily life.
The purpose of this study was to find out how safe it is for these women to take fezolinetant in long term (up to 52 weeks). To do that, the study looked at the number and severity of the "adverse events." Those were the side effects that study participants had while they were in the study.
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 looked like medicine but did not have any medicine in it.) Women in this study were picked for 1 of the 3 study treatments by chance alone. The study participants took study treatment for 52 weeks.
This study 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).
At weeks 2 and 4 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 were collected for laboratory tests. At some study visits, study participants completed questionnaires that were about their quality of life. At the first and last study visits, they had a dual-energy x-ray absorptiometry (DXA for short) test done. To measure bone loss in the hips and spine, DXA created pictures of the inside of these areas with low-dose x-rays. (The dose was approximately one-tenth of the amount of a normal chest x-ray.) Study participants who still had their uterus had 2 more 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. It 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 might have had 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 done at the last study visit if they were due for their screening mammogram and their own doctor agreed.
The last check-up at the hospital or clinic was at 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 > 40 IU/L), or
- Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
- Subject is seeking treatment for relief for VMS associated with menopause.
- 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 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 mammogram findings (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). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit.
- Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT) or the ED visit for subjects who are withdrawn from the study prior to completion, and any time during the study in the case of uterine bleeding. 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 [CYP] 1A2 inhibitors, hormone replacement therapy [HRT], hormonal contraceptive, any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue such drugs for the full extent of the study.
- Subject has a 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 a 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 hyperplasia, endometrial cancer, or other clinically significant findings at screening.
- Subje
Data sourced from ClinicalTrials.gov (NCT04003389). 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.