MedPath

A Study of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause

Phase 3
Completed
Conditions
Vasomotor Symptoms
Interventions
Drug: placebo
Registration Number
NCT05033886
Lead Sponsor
Astellas Pharma Global Development, Inc.
Brief Summary

This study is for women in menopause who have moderate to severe hot flashes. It is for women who are unable to use hormone replacement therapy (HRT). Menopause, a normal part of life, is the time after a woman's last period. Hot flashes often occur during menopause. They can disrupt a woman's daily life.

The study medicines (also called investigational products, or IP) are tablets of fezolinetant or placebo. An investigational product means that the product is not yet licensed. In this study, a placebo is a dummy treatment that looks like fezolinetant but does not have any medicine in it. The study will compare fezolinetant with the placebo to learn if fezolinetant reduces the number and severity of hot flashes.

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. In the last 10 days before their next clinic visit, the women will record information about their hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. Women will be picked for 1 of 2 treatments (fezolinetant or placebo) by chance alone.

Women who take part in the study will take 2 tablets every day for 24 weeks. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study medicines (fezolinetant or placebo). The women will continue recording information about their hot flashes on the electronic device or their phone. They will also use another device to answer questions about how hot flashes affect their daily life.

During the study, the women will visit their study clinic several times for a check-up. This will happen during Weeks 2, 4, 8, 12, 16, 20, 24, and 27. Some women may be able to have home visits instead, from Week 2 to Week 20. At the check-up, they will be asked if they have any medical problems. Other checks will include vital signs (heart rate, temperature and blood pressure) and some blood samples taken for laboratory tests. At some check-ups, the women will have a physical exam. In Week 2 and Week 24, the women will have an ECG to check their heart rhythm. Women who have a 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 check-up (at Week 27) will be 3 weeks after they take their last tablets of study medicine (fezolinetant or placebo).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
453
Inclusion Criteria

Not provided

Exclusion Criteria
  • Participant uses a prohibited therapy for VMS (e.g., prescription, over-the-counter or herbal) prior to screening and for the duration of treatment with investigational product (IP).
  • Participant has known documented substance abuse or alcohol addiction within 6 months of screening.
  • Participant has history of a malignant tumor within the last 5 years, except for basal cell carcinoma.
  • Participant has endometrial thickness > 8 mm on the locally read screening transvaginal ultrasound (TVU) or any clinically significant findings that that would make the participant ineligible.
  • Participant has history of severe allergy, hypersensitivity or intolerance to the IP and/or any of its excipients.
  • Participant has a history of seizures or other convulsive disorders unless well controlled.
  • Participant has a medical condition or chronic disease (including history of neurological [including cognitive], renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine or gynecological disease) or malignancy that could confound interpretation of the study outcome.
  • Participant has any of the following: active liver disease, jaundice, elevated liver aminotransferases at screening (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total bilirubin (TBL) or direct bilirubin (DBL) > 1.5 × upper limit of normal (ULN), elevated International Normalized Ratio (INR) > 1.5 (unless participant is receiving anticoagulant therapy) or elevated alkaline phosphatase (ALP). Participants with mildly elevated ALT or AST up to 1.5 × ULN can be enrolled if TBL and DBL are normal. Participants 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. Participants 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 <= 59 mL/min per 1.73 m^2 at the screening visit.
  • Participant has a history of suicide attempt or suicidal behavior within the last 12 months.
  • Participant has participated in another interventional study within the last 30 days prior to screening and for the duration of the study.
  • Participant who has been previously enrolled in a clinical study with fezolinetant.
  • Participant is unable or unwilling to complete the study procedures.
  • Participant has any condition makes the participant unsuitable for study participation.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplaceboParticipants receive placebo matched to fezolinetant tablets orally once daily for 24 weeks of treatment.
fezolinetantfezolinetantParticipants receive fezolinetant 45 milligrams (mg) (one 30 mg tablet and one 15 mg tablet) orally once daily for 24 weeks of treatment.
Primary Outcome Measures
NameTimeMethod
Mean change in the frequency of moderate to severe VMS from baseline at week 24Baseline, week 24

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Secondary Outcome Measures
NameTimeMethod
Mean change in severity of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20Baseline, weeks 1, 4, 8, 12, 16 and 20

Severity of moderate to severe VMS per day is calculated as follows: \[(number of moderate HFs × 2) + (number of severe HFs/day × 3)\]/number of daily moderate/severe HFs. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, causing cessation of activity. Severity is zero for participants that have had no moderate or severe VMS. Higher score indicates greater severity. A negative change indicates a reduction/improvement.

Mean percent change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24Baseline, weeks 1, 4, 8, 12, 16, 20 and 24

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Mean change in the severity of moderate to severe VMS from baseline at week 24Baseline, week 24

Severity of moderate to severe VMS per day is calculated as follows: \[(number of moderate Hot Flashes (HFs) × 2) + (number of severe HFs/day × 3)\]/number of daily moderate/severe HFs. Moderate VMS is defined as sensation of heat with sweating but able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, causing cessation of activity. Severity is zero for participants that have had no moderate or severe VMS. Higher score indicates greater severity. A negative change indicates a reduction/improvement.

Mean change in the patient-reported sleep disturbance by the Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b total score) from baseline at week 24Baseline, week 24

The PROMIS SD SF 8b assesses self reported sleep disturbance over the past 7 days and includes perceptions of restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Because it assesses the participants experience of sleep disturbance, the measure does not focus on specific sleep-disorder symptoms or ask participants to report objective measures of sleep (e.g., total amount of sleep, time to fall asleep and amount of wakefulness during sleep). Responses to each of the 8 items range from 1 (no disturbed sleep) to 5 (disturbed sleep), and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the disturbed sleep. A negative value indicates a better outcome.

Mean change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20Baseline, weeks 1, 4, 8, 12, 16 and 20

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Number of participants with percent reduction of >/= 50% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24Baseline, weeks 1, 4, 8, 12, 16, 20 and 24

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Number of participants with percent reduction of >/= 75% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24Baseline, weeks 1, 4, 8, 12, 16, 20 and 24

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Number of participants with percent reduction at 100% in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24Baseline, weeks 1, 4, 8, 12, 16, 20 and 24

The frequency of moderate to severe VMS is the number of moderate to severe VMS per 24 hours. A daily frequency per week is derived by taking the mean of the data over 7 days. Moderate VMS is defined as sensation of heat with sweating/dampness but is able to continue activity. Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity.

Number of participants with Treatment Emergent Adverse Events (TEAEs)From first dose to week 27

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 be any unfavorable \& unintended sign, symptom, or disease temporally associated with the use of medicinal product (MP) whether considered related to MP. A TEAE was defined as an AE observed after starting administration of study intervention and up to 21 days after the last dose of study intervention.

Trial Locations

Locations (69)

Site FI35803

🇫🇮

Oulu, Finland

Site PL48013

🇵🇱

Bydgoszcz, Poland

Site NO47001

🇳🇴

Hamar, Norway

Site PL48004

🇵🇱

Katowice, Poland

Site PL48009

🇵🇱

Siedice, Poland

Site PL48017

🇵🇱

Skierniewice, Poland

Site PL48012

🇵🇱

Skorzewo, Poland

Site PL48010

🇵🇱

Zamosc, Poland

Site DK45002

🇩🇰

Odense, Syddanmark, Denmark

Site DK45005

🇩🇰

Arhus C, Denmark

Site BE32005

🇧🇪

Tienen, Vlaams Brabant, Belgium

Site CA15011

🇨🇦

Saint Charles Borromeee, Quebec, Canada

Site CA15005

🇨🇦

Victoriaville, Quebec, Canada

Site CZ42009

🇨🇿

Hradec Kralove, Czechia

Site CA15014

🇨🇦

Quebec City, Quebec, Canada

Site CZ42007

🇨🇿

Tabor 3, Jihocesky, Czechia

Site CA15007

🇨🇦

Quebec, Canada

Site CA15001

🇨🇦

Sherbrooke, Quebec, Canada

Site CZ42008

🇨🇿

Brno, Czechia

Site CA15010

🇨🇦

London, Ontario, Canada

Site CA15012

🇨🇦

Montreal, Quebec, Canada

Site CA15003

🇨🇦

Sarnia, Ontario, Canada

Site CZ42002

🇨🇿

Vodnany, Jihocesky, Czechia

Site CZ42010

🇨🇿

Ceske Budejovice, Czechia

Site HU36004

🇭🇺

Kecskemet, Hungary

Site DE49006

🇩🇪

Schwerin, Germany

Site DE49004

🇩🇪

Hamburg, Germany

Site CZ42003

🇨🇿

Olomouc, Czechia

Site DE49005

🇩🇪

Hamburg, Germany

Site CZ42004

🇨🇿

Pisek, Czechia

Site FR33001

🇫🇷

Nantes, France

Site CZ42011

🇨🇿

Nachod, Czechia

Site IT39006

🇮🇹

Pavia, Italy

Site CZ42005

🇨🇿

Cheb, Czechia

Site DE49002

🇩🇪

Leipzig, Germany

Site DE49008

🇩🇪

Muechen, Germany

Site CZ42006

🇨🇿

Praha 2, Czechia

Site DK45003

🇩🇰

Gandrup, Nordjylland, Denmark

Site DK45004

🇩🇰

Vejle, Syddanmark, Denmark

Site HU36002

🇭🇺

Debrecen, Hungary

Site PL48011

🇵🇱

Katowice, Poland

Site PL48007

🇵🇱

Lublin, Poland

Site IT39002

🇮🇹

Bologna, Italy

Site FI35801

🇫🇮

Kuopio, Finland

Site FR33003

🇫🇷

La Rochelle, France

Site HU36001

🇭🇺

Szekesfeherver, Hungary

Site SE46003

🇸🇪

Stockholm, Sweden

Site GB44002

🇬🇧

Coventry, United Kingdom

Site NL31001

🇳🇱

Beek, Limburg, Netherlands

Site NL31004

🇳🇱

Rotterdam, Netherlands

Site ES34005

🇪🇸

Centellas, Spain

Site PL48006

🇵🇱

Katowice, Poland

Site ES34003

🇪🇸

Leganes, Spain

Site TR90002

🇹🇷

Konak, Izmir, Turkey

Site ES34002

🇪🇸

Alcobendas, Spain

Site ES34001

🇪🇸

Madrid, Spain

Site TR90001

🇹🇷

Ankara, Mamak, Turkey

Site GB44003

🇬🇧

Orpington, United Kingdom

Site GB44007

🇬🇧

Corby, Northamptonshire, United Kingdom

Site GB44004

🇬🇧

Shipley, Yorkshire, United Kingdom

Site GB44006

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Northwood, United Kingdom

Site SE46004

🇸🇪

Qerebro, Sweden

Site SE46002

🇸🇪

Uppsala, Sweden

Site TR90008

🇹🇷

Izmir, Turkey

Site CA15009

🇨🇦

Quebec, Canada

Site CA15002

🇨🇦

Quebec, Canada

Site CA15008

🇨🇦

Brampton, Ontario, Canada

Site PL48001

🇵🇱

Szczecin, Zachodniopomorskie, Poland

Site PL48003

🇵🇱

Bialystok, Poland

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