A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Japanese Women Going Through Menopause (Starlight 2)

A Phase 3, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of Fezolinetant in Japanese Women Experiencing Vasomotor Symptoms (Hot Flashes) Associated With Menopause

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.

Researchers want to find other ways to treat hot flashes. Fezolinetant is a medicine to treat hot flashes in women going through menopause. Fezolinetant is an approved medicine in the US. Further studies are needed before it is available in other regions such as Asia.

This study will confirm if fezolintant helps reduce the number of hot flashes in Japanese women going through menopause.

Women that want to take part in the study will be given an electronic handheld device with an app to track their hot flashes. Some women may be able to use the app on their own smartphone. Before the women are assigned a treatment, they will record information about their hot flashes.

Women will either take a lower or higher dose of fezolinetant, or a placebo. This is decided by chance alone. The placebo looks like fezolinetant but will not have any medicine in it.

The women will take 2 tablets of the study medicine (lower or higher dose of fezolinetant, or the placebo) once a day for up to 12 weeks. They will either take 1 tablet of fezolinetant (higher or lower dose) and 1 placebo tablet, or they will take 2 placebo tablets. The women will continue to record information about their hot flashes on the electronic device or their smartphone.

During the study, the women will visit the study clinic a few times. At each visit they will be asked if they had any medical problems and will use an electronic device at the clinic to answer questions about how the hot flashes affect their daily life. Other checks will include a medical examination, vital signs (temperature, blood pressure and pulse). Some blood and urine samples will be taken for laboratory tests. At some visits, the women will also have an ECG to check their heart rhythm. Women who have a womb (uterus) will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs.

The last clinic visit will be 3 weeks after the women take their final tablets of the study medicine (1 tablet of lower or higher dose of fezolinetant and 1 placebo tablet, or 2 placebo tablets).

Study Overview

• Status: Recruiting
• Conditions: Hot Flashes
• Intervention / Treatment: Drug: Placebo; Drug: Fezolinetant

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Astellas Pharma Inc.; Phone Number: +81-3-3244-6500 Japanese only; Email: astellas.registration@astellas.com

Study Locations

• Japan
  • Sapporo-shi, Japan
    • Recruiting
    • NISHIKAWA Women's Health Clinic
  • Aichi
    • Nagoya-shi, Aichi, Japan
      • Recruiting
      • Daido Clinic
    • Nagoya-shi, Aichi, Japan
      • Recruiting
      • Meitetsu Hospital
    • Toyota-shi, Aichi, Japan
      • Recruiting
      • Toyota Kosei Hospital
  • Chiba
    • Chiba-shi, Chiba, Japan
      • Recruiting
      • Chiba Aoba Municipal Hospital
    • Funabashi-shi, Chiba, Japan
      • Recruiting
      • Aiiku Ladies Clinic
    • Kashiwa-shi, Chiba, Japan
      • Recruiting
      • Tsujinaka Hospital Kashiwanoha
    • Matsudo-shi, Chiba, Japan
      • Recruiting
      • Juno Vesta Clinic hatta
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
      • Recruiting
      • Mori Ladies Clinic
  • Fukushima
    • Fukushima-Shi, Fukushima, Japan
      • Recruiting
      • Nishiguchi Clinic Fujinka
  • Gunma
    • Takasaki-shi, Gunma, Japan
      • Recruiting
      • National Hospital Organization Takasaki General Medical Center
    • Takasaki-shi, Gunma, Japan
      • Recruiting
      • Sato Hospital
  • Hiroshima
    • Hiroshima City, Hiroshima, Japan
      • Recruiting
      • Sadamori Ladies Clinic
  • Hokkaido
    • Sapporo-Shi, Hokkaido, Japan
      • Recruiting
      • Social Medical Corporation Tokeidai Memorial Hospital
    • Sapporo-Shi, Hokkaido, Japan
      • Recruiting
      • Miyanomori Ladies' Clinic
    • Sapporo-shi, Hokkaido, Japan
      • Recruiting
      • Kotoni Ladies Clinic
  • Hyogo
    • Kako-gun, Hyogo, Japan
      • Recruiting
      • Kosumo Clinic
    • Nisinomiya-shi, Hyogo, Japan
      • Recruiting
      • Mari Women'S Clinic
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan
      • Recruiting
      • National Hospital Organization Kanazawa Medical Center
  • Kanagawa
    • Kamakura-City, Kanagawa, Japan
      • Recruiting
      • Shonan Kamakura General Hospital
    • Kawasaki-shi, Kanagawa, Japan
      • Recruiting
      • Kawasakieki Fumi Ladies Clinic
    • Kawasaki-shi, Kanagawa, Japan
      • Recruiting
      • Shinkawasaki Kobiki Womens Clinic
    • Kawasaki-shi, Kanagawa, Japan
      • Recruiting
      • Koukan Clinic
    • Yokohama-shi, Kanagawa, Japan
      • Recruiting
      • Motomachi Ladies Clinic
    • Yokohama-shi, Kanagawa, Japan
      • Recruiting
      • Women's Clinic LUNA Yokohama Motomachi
  • Kyoto
    • Kyoto-shi, Kyoto, Japan
      • Recruiting
      • Rakuwakai Otowa Hospital
  • Miyagi
    • Sendai-shi, Miyagi, Japan
      • Recruiting
      • Chieko Yukika Lady's Clinic
  • Oita
    • Beppu-shi, Oita, Japan
      • Recruiting
      • National Hospital Organization Beppu Medical Center
  • Okayama
    • Okayama-shi, Okayama, Japan
      • Recruiting
      • Miyabi Uro-Gyne Clinic
    • Okayama-shi, Okayama, Japan
      • Recruiting
      • Sawada Lady'S Clinic
  • Osaka
    • Kawachinagano-shi, Osaka, Japan
      • Recruiting
      • National Hospital Organization Osaka Minami Medical Center
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • GyNet Medical Corporation Minamimorimachi Ladies' Clinic
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • Kitahorie Kanade Ladies Clinic
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • Rikako Ladies Clinic
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • Chiharu Clinic
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • Tennoji Chihiro Women's Clinic
    • Osaka-shi, Osaka, Japan
      • Recruiting
      • Chayamachi Ladies Clinic
    • Sakai-shi, Osaka, Japan
      • Recruiting
      • Shimizu Ladies Clinic
    • Takatsuki-shi, Osaka, Japan
      • Recruiting
      • jMOG Medical Corporation Tanabe Ladies' Clinic
  • Saitama
    • Saitama-shi, Saitama, Japan
      • Recruiting
      • Maruyama Memorial General Hospital
  • Shiga
    • Omihachiman-shi, Shiga, Japan
      • Recruiting
      • Omihachiman Community Medical Center
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Recruiting
      • Sei Women's Clinic
    • Chiyoda-ku, Tokyo, Japan
      • Recruiting
      • Marunouchi no Mori Ladies Clinic
    • Chuo-ku, Tokyo, Japan
      • Recruiting
      • Medical Corporation Asbo Tokyo Asbo Clinic
    • Hachioji-shi, Tokyo, Japan
      • Recruiting
      • Medical Corp. Seikoukai New Medical Research System Clinic
    • Koto-ku, Tokyo, Japan
      • Recruiting
      • Toho Lounge Clinic
    • Minato-ku, Tokyo, Japan
      • Recruiting
      • Toranomon Womens Clinic
    • Musashino-shi, Tokyo, Japan
      • Recruiting
      • Kichijyoji Ladies Clinic
    • Nerima-ku, Tokyo, Japan
      • Recruiting
      • Shimamura Memorial Hospital
    • Nishitokyo-shi, Tokyo, Japan
      • Recruiting
      • Yukawa Women'S Clinic
    • Suginami-ku, Tokyo, Japan
      • Recruiting
      • Shimodaira Ladies Clinic
    • Tama-Shi, Tokyo, Japan
      • Recruiting
      • Medical Corporation Associa Tamacenter Ladies Clinic
  • Yamaguchi
    • Shunan-shi, Yamaguchi, Japan
      • Recruiting
      • Japan Community Health care Organization Tokuyama Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant confirmed as menopausal per one of the following criteria at the screening visit (visit 1):

  • Spontaneous amenorrhea for >/=12 consecutive months;
  • Spontaneous amenorrhea for >/=6 months with biochemical criteria of menopause (follicle-stimulating hormone (FSH) > 40 IU/L);
  • Having had bilateral oophorectomy >/=6 weeks prior to the screening visit (visit 1) (with or without hysterectomy); or
  • Having had hysterectomy without bilateral oophorectomy with the biochemical criteria of menopause (FSH > 40 IU/L).
• Participant must be seeking treatment or relief for vasomotor symptoms (VMS) associated with menopause and meet some set criteria related to hot flash(es) (HFs) (VMS) prior to randomization.
• Participant agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

• Participant has a history of an undiagnosed uterine bleeding within the 6 months prior to the screening visit (visit 1).
• Participant has a current malignant tumor or history (except for a participant who has not received treatment for malignant tumors for at least 5 years before informed consent acquisition and was not considered to have recurrence) of a malignant tumor except for non-metastatic basal cell carcinoma of the skin.
• 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) that could confound interpretation of the study outcome.
• Participant uses a prohibited therapy (hormone therapy, hormone replacement therapy (HRT), hormonal contraceptive, any treatment for menopausal symptoms [prescription medications, over-the-counter, or herbal/Kampo medicines] or strong or moderate cytochrome P450 1A2 (CYP1A2) inhibitors) and is not willing to wash out or discontinue use of such drugs from screening visit (visit 1) through the follow-up visit (visit 6) or it is not medically appropriate to discontinue such drugs for the duration of the study.
• Participant has been randomized/registered in a clinical study with fezolinetant previously or had previous exposure to marketed fezolinetant elsewhere.
• Participant has a present or previous history of participation in this study.
• Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening (visit 1).
• Participant has an unacceptable result from the transvaginal ultrasound (TVU) assessment at screening (i.e., full length of endometrial cavity cannot be visualized or presence of clinically significant abnormal findings).
• Participant has documentation of a clinically significant abnormal Papanicolaou (Pap) test (or equivalent cervical cytology) within the 12 months prior to the screening visit (visit 1) or at screening.
• Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated total bilirubin (TBL) or direct bilirubin (DBL), elevated international normalized ratio (INR), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to < 1.5 × upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant 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. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
• Participant has creatinine > 1.5 × ULN or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula </=30 mL/min/1.73 m^2 at screening.
• Participant has positive hepatitis serology panel (i.e., positive hepatitis B surface (HBs) antigen and/or positive hepatitis C virus (HCV) antibody) at screening. If HCV antibody test result is equivocal, hepatitis C virus ribonucleic acid (HCV RNA) test at study site is allowed. Participant can be enrolled if that result is normal or not abnormal.
• Participant is not in good general health as determined on the basis of medical history and general physical examination performed at the screening; hematology parameters, biochemistry parameters, pulse rate, blood pressure, electrocardiogram (ECG) outside the reference range for the population studied, or is showing clinically relevant deviations.
• Participant has a history of suicide attempt or suicidal behavior within the 12 months prior to study enrollment or suicidal ideation within the 12 months prior to study enrollment (a response of "yes" to question 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS)), or is at significant risk to commit suicide at day 1 (visit 2).
• Participant is unable or unwilling to complete the study procedures.
• Participant has any condition which makes the participant unsuitable for study participation.
• Participant has a known or suspected hypersensitivity to fezolinetant or any components of the formulation used.
• Participant is the investigator or a member of the study site staff.
• Participant is an employee of Astellas, the study-related contract research organizations (CROs) or site management organization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive matching placebo once daily for 12 weeks.	Drug: Placebo; oral
Experimental: Fezolinetant low dose; Participants will receive low dose of fezolinetant and placebo once daily for 12 weeks.	Drug: Placebo; oral; Drug: Fezolinetant; oral; Other Names: ESN364;; VEOZAH™
Experimental: Fezolinetant high dose; Participants will receive high dose of fezolinetant and placebo once daily for 12 weeks.	Drug: Placebo; oral; Drug: Fezolinetant; oral; Other Names: ESN364;; VEOZAH™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in the frequency of mild to severe vasomotor symptoms (VMS)	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day.	Baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with laboratory value abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to Week 15
Number of participants with vital sign abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to Week 15
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs	Number of participants with potentially clinically significant ECG values.	Up to Week 12
Mean change from baseline in the frequency of mild to severe VMS	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day.	Baseline and up to Week 12
Mean change from baseline in the frequency of moderate to severe VMS	Frequency of moderate or severe VMS events will be calculated as the sum of moderate or severe VMS events per day.	Baseline and up to Week 12
Mean percent reduction in the frequency of mild to severe VMS from baseline	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day. Mean percent reduction will be reported.	Baseline and up to Week 12
Mean percent reduction in the frequency of moderate to severe VMS from baseline	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.	Baseline and up to Week 12
Percent reduction of >/= 50% in the frequency of mild to severe VMS from baseline	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day. Percent reduction of >/= 50% will be reported.	Baseline and up to Week 12
Percent reduction of >/= 75% in the frequency of mild to severe VMS from baseline	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day. Percent reduction of >/= 75% will be reported.	Baseline and up to Week 12
Percent reduction of 100% in the frequency of mild to severe VMS from baseline	Frequency of mild, moderate or severe VMS events will be calculated as the sum of mild, moderate or severe VMS events per day. Percent reduction of 100% will be reported.	Baseline and up to Week 12
Percent reduction of >/= 50% in the frequency of moderate to severe VMS from baseline	Frequency of moderate and severe VMS events will be calculated as the sum of moderate or severe VMS events per day. Percent reduction of >/= 50% will be reported.	Baseline and up to Week 12
Percent reduction of >/= 75% in the frequency of moderate to severe VMS from baseline	Frequency of moderate and severe VMS events will be calculated as the sum of moderate or severe VMS events per day. Percent reduction of >/= 75% will be reported.	Baseline and up to Week 12
Percent reduction of 100% in the frequency of moderate to severe VMS from baseline	Frequency of moderate and severe VMS events will be calculated as the sum of moderate or severe VMS events per day. Percent reduction of 100% will be reported.	Baseline and up to Week 12
Number of participants with Adverse Events (AEs)	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.	Up to Week 15
Change from baseline in endometrial thickness	Endometrial thickness is a measure of how thick the lining of the uterus is. Endometrial thickness will be measured by transvaginal ultrasound (TVU).	Baseline and up to Week 12
Pharmacokinetics (PK) of fezolinetant in plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Up to Week 12
Pharmacokinetics (PK) of metabolite ES259564 in plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Up to Week 12

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Associate Medical Director, Astellas Pharma Inc

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2024
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: menopause;; ESN364;; vasomotor symptoms;; fezolinetant;; VEOZAH™
• Additional Relevant MeSH Terms: Hot Flashes
• Other Study ID Numbers: 2693-CL-0310; jRCT2031230571 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No