Clinical trial NCT06206408: A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Japanese Women Going Through Menopause
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hot Flashes
Keywords: menopause;
ESN364;
vasomotor symptoms;
fezolinetant;
VEOZAH™
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2024-01-16
Enrollment: 390
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Mean change from baseline in the frequency of mild to severe vasomotor symptoms (VMS)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Mean change from baseline in the frequency of mild to severe VMS
timeFrame: Baseline and up to Week 12
measure: Mean change from baseline in the frequency of moderate to severe VMS
timeFrame: Baseline and up to Week 12
measure: Mean percent reduction in the frequency of mild to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Mean percent reduction in the frequency of moderate to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of >/= 50% in the frequency of mild to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of >/= 75% in the frequency of mild to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of 100% in the frequency of mild to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of >/= 50% in the frequency of moderate to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of >/= 75% in the frequency of moderate to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Percent reduction of 100% in the frequency of moderate to severe VMS from baseline
timeFrame: Baseline and up to Week 12
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to Week 15
measure: Change from baseline in endometrial thickness
timeFrame: Baseline and up to Week 12
measure: Number of participants with laboratory value abnormalities and/or AEs
timeFrame: Up to Week 15
measure: Number of participants with vital sign abnormalities and/or AEs
timeFrame: Up to Week 15
measure: Number of participants with electrocardiogram (ECG) abnormalities and/or AEs
timeFrame: Up to Week 12
measure: Pharmacokinetics (PK) of fezolinetant in plasma: Concentration
timeFrame: Up to Week 12
measure: Pharmacokinetics (PK) of metabolite ES259564 in plasma: Concentration
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Chita-gun
country: Japan
facility: Chita Kosei Hospital
state: Aichi
city: Konan-City
country: Japan
facility: Konan Kosei Hospital
state: Aichi
city: Nagoya-shi
country: Japan
facility: Daido Clinic
state: Aichi
city: Nagoya-shi
country: Japan
facility: MEITETSU Hospital
state: Aichi
city: Toyota-shi
country: Japan
facility: Toyota Kosei Hospital
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba Aoba Municipal Hospital
state: Chiba
city: Funabashi-shi
country: Japan
facility: Aiiku Ladies Clinic
state: Chiba
city: Kashiwa-shi
country: Japan
facility: Tsujinaka Hospital Kashiwanoha
state: Chiba
city: Matsudo-shi
country: Japan
facility: Juno Vesta Clinic hatta
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Fukuoka Mirai Hospital
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Mori Ladies Clinic
state: Fukuoka
city: Fukushima-Shi
country: Japan
facility: Nishiguchi Clinic Fujinka
state: Fukushima
city: Takasaki-shi
country: Japan
facility: National Hospital Organization Takasaki General Medical Center
state: Gunma
city: Takasaki-shi
country: Japan
facility: Sato Hospital
state: Gunma
city: Hiroshima City
country: Japan
facility: Sadamori Ladies Clinic
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Kotoni Ladies Clinic
state: Hokkaido
city: Sapporo-Shi
country: Japan
facility: Miyanomori Ladies' Clinic
state: Hokkaido
city: Sapporo-Shi
country: Japan
facility: Social Medical Corporation Caress Sapporo Caress Memorial Hospital
state: Hokkaido
city: Kako-gun
country: Japan
facility: Kosumo Clinic
state: Hyogo
city: Nisinomiya-shi
country: Japan
facility: Mari Women'S Clinic
state: Hyogo
city: Toride-city
country: Japan
facility: JA Toride Medical Center
state: Ibaraki
city: Tsukuba City
country: Japan
facility: Tsukuba Urocare Clinic
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
state: Ishikawa
city: Takamatsu City
country: Japan
facility: Asahi Clinic
state: Kagawa
city: Kamakura-City
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Kawasakieki Fumi Ladies Clinic
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Koukan Clinic
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Shinkawasaki Kobiki Womens Clinic
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Motomachi Ladies Clinic
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Women's Clinic LUNA Yokohama Motomachi
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Rakuwakai Otowa Hospital
state: Kyoto
city: Sendai-shi
country: Japan
facility: Chieko Yukika Lady's Clinic
state: Miyagi
city: Matsumoto-shi
country: Japan
facility: Social Medical Care Corporation Hosei-kai Marunouchi Hospital
state: Nagano
city: Beppu-shi
country: Japan
facility: National Hospital Organization Beppu Medical Center
state: Oita
city: Okayama-shi
country: Japan
facility: Miyabi Uro-Gyne Clinic
state: Okayama
city: Okayama-shi
country: Japan
facility: Sawada Lady'S Clinic
state: Okayama
city: Kawachinagano-shi
country: Japan
facility: National Hospital Organization Osaka Minami Medical Center
state: Osaka
city: Osaka City
country: Japan
facility: Ninomiya Ladies Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: Chayamachi Ladies Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: Chiharu Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: GyNet Medical Corporation Minamimorimachi Ladies' Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: Kitahorie Kanade Ladies Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: Komorebi Ladies Clinic Osaka Honmachi
state: Osaka
city: Osaka-shi
country: Japan
facility: Rikako Ladies Clinic
state: Osaka
city: Osaka-shi
country: Japan
facility: Tennoji Chihiro Women's Clinic
state: Osaka
city: Sakai-shi
country: Japan
facility: Shimizu Ladies Clinic
state: Osaka
city: Takatsuki-shi
country: Japan
facility: jMOG Medical Corporation Tanabe Ladies' Clinic
state: Osaka
city: Saitama City
country: Japan
facility: OHARA Clinic
state: Saitama
city: Saitama-shi
country: Japan
facility: Maruyama Memorial General Hospital
state: Saitama
city: Kusatsu-shi
country: Japan
facility: Omi Medical Center, Social Medical Corporation Seikoukai
state: Shiga
city: Omihachiman-shi
country: Japan
facility: Omihachiman Community Medical Center
state: Shiga
city: Bunkyo-ku
country: Japan
facility: Sei Women's Clinic
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Marunouchi no Mori Ladies Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Medical Corporation Asbo Tokyo Asbo Clinic
state: Tokyo
city: Hachioji-shi
country: Japan
facility: Medical Corp. SEIKOUKAI New Medical Research System Clinic
state: Tokyo
city: Koto-ku
country: Japan
facility: Toho Lounge Clinic
state: Tokyo
city: Machida-shi
country: Japan
facility: Machida Municipal Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Toranomon Womens Clinic
state: Tokyo
city: Musashino-shi
country: Japan
facility: Kichijyoji Ladies Clinic
state: Tokyo
city: Nerima-ku
country: Japan
facility: Shimamura Memorial Hospital
state: Tokyo
city: Nishitokyo-shi
country: Japan
facility: Yukawa Women'S Clinic
state: Tokyo
city: Suginami-ku
country: Japan
facility: Shimodaira Ladies Clinic
state: Tokyo
city: Tama-Shi
country: Japan
facility: Medical Corporation Associa Tamacenter Ladies Clinic
state: Tokyo
city: Shunan-shi
country: Japan
facility: Japan Community Health care Organization Tokuyama Central Hospital
state: Yamaguchi
city: Sapporo-shi
country: Japan
facility: NISHIKAWA Women's Health Clinic
Study officials:
affiliation: Astellas Pharma Inc
name: Associate Medical Director
role: STUDY_DIRECTOR
References: