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A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Chinese Women Going Through Menopause

Phase 2
Recruiting
Conditions
Hot Flashes
Interventions
Drug: Placebo
Registration Number
NCT06812754
Lead Sponsor
Astellas Pharma Global Development, Inc.
Brief Summary

Hot flashes are the most common reason women going through menopause seek medical attention. Hormone replacement therapy, or HRT, is most often prescribed to treat hot flashes. However, HRT can't be used by all women or for as long as may be needed.

Fezolinetant is approved in several countries to treat hot flashes in women going through menopause. Further studies are needed before it is available in other regions such as Asia.

The goal of this study is to confirm if fezolinetant helps reduce hot flashes in Chinese women going through menopause. This study will also confirm the safety of fezolinetant and how well the women cope with (tolerate) the treatment. The women will take 1 tablet of the study medicine either fezolinetant or placebo once a day for up to 12 weeks. This is decided by chance alone. The placebo looks like fezolinetant but will not have any medicine in it.

Women that want to take part in the study will be given an electronic handheld device with an app to track their hot flashes and night sweats. The women will record this information before, during and after taking the study treatment. During the study, the women will visit the study clinic several times. At each visit they will be asked if they had any medical problems. The women will have general safety checks. At some visits, a breast ultrasound (mammogram), cervical smear, and ultrasound of the womb (uterus) may be done.

The last clinic visit will be 3 weeks after the women take their final tablet of the study medicine (fezolinetant or placebo).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
150
Inclusion Criteria
  • Participant has a body mass index >/= 16 kg/m2 and </= 38 kg/m2 at screening visit.

  • Participant must be seeking treatment or relief for vasomotor symptom(s) (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 (with or without hysterectomy).
    • FSH > 40 IU/L if participants received hysterectomy but still have an ovary/ovaries.
  • Within the 10 days prior to randomization, participant must have a minimum average of 7 moderate to severe hot flash(es) (HFs) (VMS) per day (data must be available for at least 7 of the last 10 days prior to randomization).

  • Participant is in good general health as determined on the basis of medical history and general physical examination, 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.

  • Participant has documentation of a normal/negative or no clinically significant findings mammogram (or breast ultrasound) (e.g., < Breast Imaging-Reporting and Data System (BI-RADS) class 4; 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.

  • Participant is willing to undergo a transvaginal ultrasound (TVU) to evaluate the uterus and ovaries at screening and week 12 (end of treatment (EOT)), and for participants who are withdrawn from the study prior to completion, a TVU at the early discontinuation (ED) visit. This is not required for participants who have had a partial (supracervical) or total hysterectomy.

  • Participant has documentation of a normal or not clinically significant Pap test (or equivalent cervical cytology) within the previous 12 months of study enrollment or at screening. This is not required for participants who have had a total hysterectomy.

  • Participant has a negative urine pregnancy test at screening; this is not required for participants who have had a total hysterectomy.

  • Participant has a negative serology panel [i.e., negative hepatitis B surface antigen (HBsAg) and negative hepatitis C virus antibody (HCVAb) screens] at screening.

  • Participant agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria
  • Participant has known substance abuse or alcohol addiction within 6 months of screening.

  • Participant has a current malignancy, with exception of non-metastatic basal cell carcinoma of the skin.

  • Participant has a history of malignancy with exceptions of at least 5 years post-treatment and without known recurrence.

  • For participants with a uterus: Participant 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.

  • Participant has a history within the last 6 months of undiagnosed uterine bleeding.

  • Participant 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.

  • Participant 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 question 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 at screening [visit 1].

  • Participant has previously been enrolled in a clinical trial with fezolinetant or other neurokinin (NK) receptor antagonists.

  • Participant uses a prohibited therapy (strong and 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.

  • Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.

  • Participant has uncontrolled hypertension, defined as systolic blood pressure >/=140 mmHg or diastolic blood pressure as >/= 90 mmHg based on an average of 2 to 3 readings within the screening period.

    • Participants with a medical history of hypertension who are well controlled may be enrolled
    • Participants who do not meet these criteria may be re-assessed after initiation or review of antihypertensive measures
  • Participant has active liver disease, jaundice, 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 × upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Patients with mildly elevated ALP (up to 1.5 × 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 (TBL) may be enrolled as long as hemolysis is ruled-out (i.e., direct bilirubin, hemoglobin and reticulocytes are normal).

  • Participant has creatinine > 1.5 × ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula </=30 mL/min/1.73 m2 at screening.

  • Participant has a positive result for human immunodeficiency virus (HIV) at screening.

  • Participant has any condition which makes the participant unsuitable for study participation.

  • Participant is unable or unwilling to complete the study procedures.

  • Participant has a known or suspected hypersensitivity to fezolinetant or any components of the formulation used.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FezolinetantFezolinetantParticipants will receive fezolinetant once daily for 12 weeks.
PlaceboPlaceboParticipants will receive matching placebo once daily for 12 weeks.
Primary Outcome Measures
NameTimeMethod
Mean change in the frequency of moderate to severe Vasomotor Symptoms (VMS) from baseline to week 12Baseline to Week 12

Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.

Secondary Outcome Measures
NameTimeMethod
Mean change in the frequency of moderate to severe VMS from baseline to each week up to week 12Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.

Mean change in the severity of moderate to severe VMS from baseline to week 12Baseline to Week 12

The severity of VMS will be calculated using a weighted average of VMS events.

Mean change in the severity of moderate to severe VMS from baseline to each week up to week 12Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

The severity of VMS will be calculated using a weighted average of VMS events.

Mean percent reduction in the frequency of moderate to severe VMS from baseline to each week up to week 12Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Frequency of moderate and severe VMS events will be calculated as the sum of moderate or severe VMS events per day. Mean percent reduction will be reported.

Percent reduction >/= 50% in the frequency of moderate to severe VMS from baseline to each week up to week 12Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of \>/= 50% will be reported.

Percent reduction at 100% in the frequency of moderate to severe VMS from baseline to each week up to week 12Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of 100% will be reported.

Number of participants with Adverse Events (AEs)Up to Week 15

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.

Change from baseline in endometrial thickness in post-menopausal participantsBaseline up to Week 12

Endometrial thickness is a measure of how thick the lining of the uterus is. Endometrial thickness will be measured by transvaginal ultrasound (TVU).

Number of participants with laboratory value abnormalities and/or adverse events (AEs)Up to Week 15

Number of participants with potentially clinically significant laboratory values.

Number of participants with vital sign abnormalities and/or adverse events (AEs)Up to Week 15

Number of participants with potentially clinically significant vital sign values.

Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)Up to Week 12

Number of participants with potentially clinically significant ECG values.

Pharmacokinetics (PK) of Fezolinetant in plasma: ConcentrationUp to Week 12

Concentration will be recorded from the PK plasma samples collected.

Pharmacokinetics (PK) of metabolite ES259564 in plasma: ConcentrationUp to Week 12

Concentration will be recorded from the PK plasma samples collected.

Change in serum concentrations of sex hormonesBaseline up to Week 15

Sex hormone biomarker levels will be recorded from serum samples.

Trial Locations

Locations (22)

Beijing Hospital

🇨🇳

Beijing, Beijing, China

Capital Medical University (CMU) - Beijing Shijitan Hospital

🇨🇳

Beijing, Beijing, China

Peking University Shenzhen Hospital

🇨🇳

Shenzhen, Guangdong, China

Liuzhou Worker's Hospital

🇨🇳

Liuzhou, Guangxi, China

Jinan Central Hospital Affiliated to Shandong First Medical University

🇨🇳

Jinan, Shandong, China

Shanxi Woman and Children Hospital

🇨🇳

Taiyuan, Shanxi, China

The First hospital of Shanxi Medical University

🇨🇳

Taiyuan, Shanxi, China

The Second Hospital of Tianjin Medical University

🇨🇳

Tianjin, Tianjin, China

Hangzhou First People's Hospital

🇨🇳

Hangzhou, Zhejiang, China

Shenzhen Maternal & Child Health Hospital

🇨🇳

Shenzhen, Guangdong, China

Guangxi Medical University (GXMU) - Liuzhou Renmin Hospital

🇨🇳

Liuzhou, Guangxi, China

Peking Union Medical College Hospital

🇨🇳

Beijing, Beijing, China

Guangzhou Medical University - The Third Affiliated Hospital

🇨🇳

Guangzhou, Guangdong, China

Jiangxi Maternal and Child Health Hospital

🇨🇳

Nan Chang, Jiang XI, China

Nanjing First Hospital

🇨🇳

Nanjing, Jiangsu, China

Southeast University, ZhongDa Hospital

🇨🇳

Nanjing, Jiangsu, China

The second Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Hunan Provincial Maternal and Child Health Care Hospital

🇨🇳

Changsha, Hunan, China

Xiangya Hospital, Central South University

🇨🇳

Zhuzhou, Hunan, China

Jilin Province FAW General Hospital

🇨🇳

Changchun, Jilin, China

Shandong Provincial Hospital

🇨🇳

Jinan, Shandong, China

Chengdu Women's and Children's Central Hospital

🇨🇳

Chengdu, Sichuan, China

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