A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause (Skylight 4)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04003389 |
|
Recruitment Status :
Completed
First Posted : July 1, 2019
Results First Posted : February 1, 2023
Last Update Posted : September 21, 2023
|
Sponsor:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hot Flashes | Drug: fezolinetant Drug: placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1831 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | July 10, 2019 |
| Actual Primary Completion Date : | January 4, 2022 |
| Actual Study Completion Date : | January 4, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Fezolinetant 30 mg
Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, once daily (QD) for a period of 52 Weeks.
|
Drug: fezolinetant
administered orally |
|
Experimental: Fezolinetant 45 mg
Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD for a period of 52 Weeks.
|
Drug: fezolinetant
administered orally |
|
Placebo Comparator: Placebo
Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, QD for a of period of 52 Weeks.
|
Drug: placebo
administered orally |
Primary Outcome Measures :
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug until 21 days after last dose of study drug (Up to 55 weeks) ]An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign, symptom, or disease temporally associated with the use of medicinal product (MP) whether or not considered related to MP. An AE is considered "serious" if it results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires inpatient hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. A TEAE is defined as an AE observed after starting administration of study drug & 21 days after the last dose of study drug.
- Number of Participants With Mild, Moderate and Severe TEAE [ Time Frame: From first dose of study drug until 21 days after last dose of study drug (Up to 55 weeks) ]An adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. A TEAE is defined as an AE observed after starting administration of the study drug and 21 days after the last dose of study drug. Severity of AE we were classified as Mild: No disruption of normal daily activities; Moderate: Affect normal daily activities; and Severe: Inability to perform daily activities.
- Percentage of Participants With Endometrial Hyperplasia [ Time Frame: Baseline Up to 52 weeks ]Endometrial hyperplasia was confirmed from the endometrial biopsy report.
- Percentage of Participants With Endometrial Cancer [ Time Frame: Baseline Up to 52 weeks ]Endometrial cancer was confirmed from the endometrial biopsy report.
Secondary Outcome Measures :
- Change From Baseline in Endometrial Thickness at Week 52 [ Time Frame: Baseline and week 52 ]Endometrial thicness was obtained from the transvaginal ultrasound. The endometrium was measured in the long axis or sagittal plane. The measurement was of the thickest echogenic area from 1 basal endometrial interface across the endometrial canal to the other basal surface.
- Percentage of Participants With Disordered Proliferative Endometrium [ Time Frame: Baseline Up to 52 weeks ]Disordered proliferative endometrium was confirmed from the endometrial biopsy report.
- Change From Baseline in Bone Mineral Density (BMD) at Hip at Week 52 [ Time Frame: Baseline and week 52 ]Changes in BMD hip was assessed by dual-energy X-ray absorptiometry (DXA) scan.
- Change From Baseline in Trabecular Bone Score (TBS) at Hip at Week 52 [ Time Frame: Baseline and week 52 ]TBS was a bone texture assessment that serves as a substitute for bone microarchitecture and predicts fracture risk independent of BMD and clinical risk factors. The DXA imaging was processed and analyzed as it would normally be and then evaluated using an automated algorithm to determine the TBS. T-score ≥1.350 was considered to be normal; T-score between 1.200 and 1.350 is considered to be consistent with partially degraded microarchitecture; and T-score ≤1.200 defines degraded microarchitecture.
- Change From Baseline in BMD at Spine at Week 52 [ Time Frame: Baseline and week 52 ]Changes in BMD spine was assessed by DXA scan.
- Change From Baseline in TBS at Spine at Week 52 [ Time Frame: Baseline and week 52 ]TBS was a bone texture assessment that serves as a substitute for bone microarchitecture and predicts fracture risk independent of BMD and clinical risk factors. The DXA imaging was processed and analyzed as it would normally be and then evaluated using an automated algorithm to determine the TBS. T-score ≥1.350 was considered to be normal; T-score between 1.200 and 1.350 is considered to be consistent with partially degraded microarchitecture; and T-score ≤1.200 defines degraded microarchitecture.
- Number of Participants With Suicidal Ideation and/or Behaviour as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline, week 12, week 24, week 52 and follow-up (week 55) ]The C-SSRS assessed the risk for suicidal behavior and suicide ideation. Participants responded as "Yes" or "No" 10 items. Suicidal ideation (1. Wish to be dead; 2. Non-specific active suicidal thoughts; 3. Active suicidal ideation with any methods (not plan) without intent to act; 4. Active suicidal ideation with some intent to act, without specific plan; 5. Active suicidal ideation with specific plan and intent; ). Suicidal behaviour (1. Preparatory acts or behavior 2. Aborted attempt 3. Interrupted attempt 4. Actual attempt 5. Completed suicide). Participants with 'Yes' to any one of the above 10 questions for suicidal ideation and behavior were reported.
- Number of Participants With Self-injurious Behavior Without Suicidal Intent as Assessed by C-SSRS [ Time Frame: Baseline, week 12, week 24, week 52 and follow-up (week 55) ]The C-SSRS assessed the risk for Self-injurious Behavior without Suicidal Intent. Question was asked "Has participant engaged in Non-Suicidal Self-Injurious Behavior?". Participants with 'yes' to the question were reported.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 40 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
- Subject has a history within the last 6 months of undiagnosed uterine bleeding.
- Subject has a history of seizures or other convulsive disorders.
- Subject has a medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine or gynecological disease) or malignancy that could confound interpretation of the study outcome.
- Subject has active liver disease, jaundice or elevated liver aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total or direct bilirubin, elevated international normalized ratio (INR), or elevated alkaline phosphatase (ALP). Patients with mildly elevated ALT or AST up to 1.5 times the upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Patients with mildly elevated ALP (up to 1.5 x ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Patients with Gilbert's syndrome with elevated total bilirubin may be enrolled as long as direct bilirubin, hemoglobin and reticulocytes are normal.
- Subject has creatinine > 1.5 x ULN; or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula ≤ 59 mL/min per 1.73 m^2 at the screening visit.
- Subject has a history of suicide attempt or suicidal behavior within the last 12 months or has suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale [C-SSRS]), or who is at significant risk to commit suicide, as assessed at screening and at the time of visit 2 (randomization).
- Subject has previously been enrolled in a clinical trial with fezolinetant.
- Subject is participating concurrently in another interventional study or participated in an interventional study within 28 days prior to screening, or received any investigational drug within 28 days or within 5 half-lives prior to screening, whichever is longer.
- Subject is unable or unwilling to complete the study procedures.
- Subject has any condition which makes the subject unsuitable for study participation.
- Subject has had a partial or full hysterectomy.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04003389
Locations
Show 182 study locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
| Study Director: | Executive Medical Director | Astellas Pharma Global Development, Inc. |
Study Documents (Full-Text)
Documents provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Documents provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Study Protocol [PDF] March 19, 2021
Statistical Analysis Plan [PDF] December 8, 2021
Additional Information:
| Responsible Party: | Astellas Pharma Global Development, Inc. |
| ClinicalTrials.gov Identifier: | NCT04003389 |
| Other Study ID Numbers: |
2693-CL-0304 2019-000275-16 ( EudraCT Number ) |
| First Posted: | July 1, 2019 Key Record Dates |
| Results First Posted: | February 1, 2023 |
| Last Update Posted: | September 21, 2023 |
| Last Verified: | September 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data |
| Access Criteria: | Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement. |
| URL: | https://www.clinicalstudydatarequest.com/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
|
menopause fezolinetant ESN364 vasomotor symptoms |
Additional relevant MeSH terms:
|
Hot Flashes |