Clinical trial NCT05033886: A Study of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause
Official title: A Phase 3b, Randomized, Double-blind, Placebo-controlled, 24-week Study to Assess the Efficacy and Safety of Fezolinetant in Menopausal Women Suffering From Moderate to Severe Vasomotor Symptoms (Hot Flashes) and Considered Unsuitable for Hormone Replacement Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vasomotor Symptoms
Keywords: ESN364
menopause
fezolinetant
vasomotor symptoms
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2021-09-05
Enrollment: 453
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: 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).


Eligibility criteria: Inclusion Criteria :

* Participant must be seeking treatment or relief for vasomotor symptoms (VMS) associated with menopause and confirmed as menopausal per one of the following criteria at the screening visit:

  * Spontaneous amenorrhea for \>= 12 consecutive months
  * Spontaneous amenorrhea for \>= 6 months with biochemical criterion of menopause (follicle-stimulating hormone \[FSH\] \> 40 IU/L)
  * Had bilateral oophorectomy \>= 6 weeks prior to the screening visit (with or without hysterectomy)
* Participant has VMS and is unsuitable to receive hormone replacement therapy (HRT) (HRT contraindicated, HRT caution, HRT stoppers and HRT averse participants).
* Participant has a minimum average of 7 moderate to severe hot flash's (HFs) (VMS) per day as recorded in the electronic diary during the last 10 days prior to randomization.
* Participant is in good general health as determined on the basis of medical history, general physical examination, laboratory and other medical assessments.
* Participant has a negative serology panel (including hepatitis B surface antigen, hepatitis C virus antibody and human immunodeficiency virus antibody screens).
* Had hysterectomy without oophorectomy and who meets the biochemical criterion of menopause (FSH \> 40 IU/L).

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.

Primary outcomes:
measure: Mean change in the frequency of moderate to severe VMS from baseline at week 24
timeFrame: Baseline, week 24
Secondary outcomes:
measure: Mean change in the severity of moderate to severe VMS from baseline at week 24
timeFrame: Baseline, week 24
measure: 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 24
timeFrame: Baseline, week 24
measure: Mean change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20
timeFrame: Baseline, weeks 1, 4, 8, 12, 16 and 20
measure: Mean change in severity of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16 and 20
timeFrame: Baseline, weeks 1, 4, 8, 12, 16 and 20
measure: Mean percent change in the frequency of moderate to severe VMS from baseline at weeks 1, 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, weeks 1, 4, 8, 12, 16, 20 and 24
measure: 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 24
timeFrame: Baseline, weeks 1, 4, 8, 12, 16, 20 and 24
measure: 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 24
timeFrame: Baseline, weeks 1, 4, 8, 12, 16, 20 and 24
measure: 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 24
timeFrame: Baseline, weeks 1, 4, 8, 12, 16, 20 and 24
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose to week 27
Other outcomes:
Locations:
city: Tienen
country: Belgium
facility: Site BE32005
state: Vlaams Brabant
city: Brampton
country: Canada
facility: Site CA15008
state: Ontario
city: London
country: Canada
facility: Site CA15010
state: Ontario
city: Sarnia
country: Canada
facility: Site CA15003
state: Ontario
city: Montreal
country: Canada
facility: Site CA15012
state: Quebec
city: Quebec City
country: Canada
facility: Site CA15014
state: Quebec
city: Saint Charles Borromeee
country: Canada
facility: Site CA15011
state: Quebec
city: Sherbrooke
country: Canada
facility: Site CA15001
state: Quebec
city: Victoriaville
country: Canada
facility: Site CA15005
state: Quebec
city: Quebec
country: Canada
facility: Site CA15002
city: Quebec
country: Canada
facility: Site CA15009
city: Quebec
country: Canada
facility: Site CA15007
city: Tabor 3
country: Czechia
facility: Site CZ42007
state: Jihocesky
city: Vodnany
country: Czechia
facility: Site CZ42002
state: Jihocesky
city: Brno
country: Czechia
facility: Site CZ42008
city: Ceske Budejovice
country: Czechia
facility: Site CZ42010
city: Cheb
country: Czechia
facility: Site CZ42005
city: Hradec Kralove
country: Czechia
facility: Site CZ42009
city: Nachod
country: Czechia
facility: Site CZ42011
city: Olomouc
country: Czechia
facility: Site CZ42003
city: Pisek
country: Czechia
facility: Site CZ42004
city: Praha 2
country: Czechia
facility: Site CZ42006
city: Gandrup
country: Denmark
facility: Site DK45003
state: Nordjylland
city: Odense
country: Denmark
facility: Site DK45002
state: Syddanmark
city: Vejle
country: Denmark
facility: Site DK45004
state: Syddanmark
city: Arhus C
country: Denmark
facility: Site DK45005
city: Kuopio
country: Finland
facility: Site FI35801
city: Oulu
country: Finland
facility: Site FI35803
city: La Rochelle
country: France
facility: Site FR33003
city: Nantes
country: France
facility: Site FR33001
city: Hamburg
country: Germany
facility: Site DE49004
city: Hamburg
country: Germany
facility: Site DE49005
city: Leipzig
country: Germany
facility: Site DE49002
city: Muechen
country: Germany
facility: Site DE49008
city: Schwerin
country: Germany
facility: Site DE49006
city: Debrecen
country: Hungary
facility: Site HU36002
city: Kecskemet
country: Hungary
facility: Site HU36004
city: Szekesfeherver
country: Hungary
facility: Site HU36001
city: Bologna
country: Italy
facility: Site IT39002
city: Pavia
country: Italy
facility: Site IT39006
city: Beek
country: Netherlands
facility: Site NL31001
state: Limburg
city: Rotterdam
country: Netherlands
facility: Site NL31004
city: Hamar
country: Norway
facility: Site NO47001
city: Szczecin
country: Poland
facility: Site PL48001
state: Zachodniopomorskie
city: Bialystok
country: Poland
facility: Site PL48003
city: Bydgoszcz
country: Poland
facility: Site PL48013
city: Katowice
country: Poland
facility: Site PL48006
city: Katowice
country: Poland
facility: Site PL48011
city: Katowice
country: Poland
facility: Site PL48004
city: Lublin
country: Poland
facility: Site PL48007
city: Siedice
country: Poland
facility: Site PL48009
city: Skierniewice
country: Poland
facility: Site PL48017
city: Skorzewo
country: Poland
facility: Site PL48012
city: Zamosc
country: Poland
facility: Site PL48010
city: Alcobendas
country: Spain
facility: Site ES34002
city: Centellas
country: Spain
facility: Site ES34005
city: Leganes
country: Spain
facility: Site ES34003
city: Madrid
country: Spain
facility: Site ES34001
city: Qerebro
country: Sweden
facility: Site SE46004
city: Stockholm
country: Sweden
facility: Site SE46003
city: Uppsala
country: Sweden
facility: Site SE46002
city: Konak
country: Turkey
facility: Site TR90002
state: Izmir
city: Ankara
country: Turkey
facility: Site TR90001
state: Mamak
city: Izmir
country: Turkey
facility: Site TR90008
city: Corby
country: United Kingdom
facility: Site GB44007
state: Northamptonshire
city: Shipley
country: United Kingdom
facility: Site GB44004
state: Yorkshire
city: Coventry
country: United Kingdom
facility: Site GB44002
city: Northwood
country: United Kingdom
facility: Site GB44006
city: Orpington
country: United Kingdom
facility: Site GB44003
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Medical Director
role: STUDY_DIRECTOR
References: