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

Hot Flashes Clinical Trial

— Starlight 2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206408
• Other study ID #: 2693-CL-0310
• Secondary ID: jRCT2031230571
• Status: Recruiting
• Phase: Phase 3
• Start date: February 16, 2024
• Est. completion date: March 31, 2026

Study information

• Verified date: June 2024
• Source: Astellas Pharma Inc
• Contact: Astellas Pharma Inc.
• Phone: +81-3-3244-6500 Japanese only
• Email: astellas.registration[@]astellas.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: March 31, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• Fezolinetant
oral
• Placebo
oral

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants with laboratory value abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to Week 15
Secondary	Number of participants with vital sign abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to Week 15
Secondary	Number of participants with electrocardiogram (ECG) abnormalities and/or AEs	Number of participants with potentially clinically significant ECG values.	Up to Week 12
Secondary	Pharmacokinetics (PK) of fezolinetant in plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Up to Week 12
Secondary	Pharmacokinetics (PK) of metabolite ES259564 in plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Up to Week 12