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

NCT05033886 | Completed Phase 3 DMC

• 2 other identifiers: 2693-CL-03122021-001685-38
• Study Type: interventional
• Target: 453
• Locations: 16 countries
• Sites: 69

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).

Conditions

Vasomotor Symptoms

Keywords

ESN364; menopause; fezolinetant; vasomotor symptoms

Outcome Measures

Primary Outcomes (1)

• Mean change in the frequency of moderate to severe VMS from baseline at 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.

  Baseline, week 24

Secondary Outcomes (9)

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

  Baseline, week 24

• 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

  Baseline, week 24

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

  Baseline, weeks 1, 4, 8, 12, 16 and 20

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

  Baseline, weeks 1, 4, 8, 12, 16 and 20

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

  Baseline, weeks 1, 4, 8, 12, 16, 20 and 24

Study Arms (2)

fezolinetant

EXPERIMENTAL

Participants receive fezolinetant 45 milligrams (mg) (one 30 mg tablet and one 15 mg tablet) orally once daily for 24 weeks of treatment.

Drug: fezolinetant

placebo

PLACEBO COMPARATOR

Participants receive placebo matched to fezolinetant tablets orally once daily for 24 weeks of treatment.

Drug: placebo

Interventions

fezolinetant DRUG

oral

Also known as: ESN364

fezolinetant

placebo DRUG

oral

placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (69)

Site BE32005

Tienen, Vlaams Brabant, 3300, Belgium

Location

Site CA15008

Brampton, Ontario, L6T 0G1, Canada

Location

Site CA15010

London, Ontario, N5W 6A2, Canada

Location

Site CA15003

Sarnia, Ontario, N7T 4X3, Canada

Location

Site CA15012

Montreal, Quebec, H1M 1B1, Canada

Location

Site CA15014

Québec, Quebec, G3K 2P8, Canada

Location

Site CA15011

Saint Charles Borromeee, Quebec, J6E 2B4, Canada

Location

Site CA15001

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Site CA15005

Victoriaville, Quebec, G6P 6P6, Canada

Location

Site CA15002

Québec, G1S 2L6, Canada

Location

Site CA15009

Québec, G1S 2L6, Canada

Location

Site CA15007

Québec, G1W 4R4, Canada

Location

Site CZ42007

Tábor, Jihočeský kraj, 39003, Czechia

Location

Site CZ42002

Vodňany, Jihočeský kraj, 389 01, Czechia

Location

Site CZ42008

Brno, 603 00, Czechia

Location

Site CZ42005

Cheb, 350 02, Czechia

Location

Site CZ42010

České Budějovice, 37001, Czechia

Location

Site CZ42009

Hradec Králové, 500 02, Czechia

Location

Site CZ42011

Náchod, 54701, Czechia

Location

Site CZ42003

Olomouc, 772 00, Czechia

Location

Site CZ42004

Písek, 397 01, Czechia

Location

Site CZ42006

Prague, 120 00, Czechia

Location

Site DK45003

Gandrup, North Denmark, 9362, Denmark

Location

Site DK45002

Odense, Region Syddanmark, 5000, Denmark

Location

Site DK45004

Vejle, Region Syddanmark, 7100, Denmark

Location

Site DK45005

Arhus C, 8000, Denmark

Location

Site FI35801

Kuopio, 02200, Finland

Location

Site FI35803

Oulu, 02200, Finland

Location

Site FR33003

La Rochelle, 17000, France

Location

Site FR33001

Nantes, 44093, France

Location

Site DE49004

Hamburg, 20253, Germany

Location

Site DE49005

Hamburg, 22159, Germany

Location

Site DE49002

Leipzig, 10026, Germany

Location

Site DE49008

Muechen, 12092, Germany

Location

Site DE49006

Schwerin, 19055, Germany

Location

Site HU36002

Debrecen, 4024, Hungary

Location

Site HU36004

Kecskemét, 6000, Hungary

Location

Site HU36001

Szekesfeherver, 8000, Hungary

Location

Site IT39002

Bologna, 12081, Italy

Location

Site IT39006

Pavia, 27100, Italy

Location

Site NL31001

Beek, Limburg, 6191 JW, Netherlands

Location

Site NL31004

Rotterdam, 3051 GV, Netherlands

Location

Site NO47001

Hamar, 2317, Norway

Location

Site PL48001

Szczecin, West Pomeranian Voivodeship, 71-434, Poland

Location

Site PL48003

Bialystok, 15-224, Poland

Location

Site PL48013

Bydgoszcz, 85-048, Poland

Location

Site PL48006

Katowice, 40-065, Poland

Location

Site PL48011

Katowice, 40-156, Poland

Location

Site PL48004

Katowice, 40-301, Poland

Location

Site PL48007

Lublin, 20-064, Poland

Location

Site PL48009

Siedice, 08-110, Poland

Location

Site PL48017

Skierniewice, 96-100, Poland

Location

Site PL48012

Skorzewo, 60185, Poland

Location

Site PL48010

Zamość, 22 400, Poland

Location

Site ES34002

Alcobendas, 28100, Spain

Location

Site ES34005

Centellas, 8540, Spain

Location

Site ES34003

Leganés, 28915, Spain

Location

Site ES34001

Madrid, 28041, Spain

Location

Site SE46004

Qerebro, 435 33, Sweden

Location

Site SE46003

Stockholm, 17176, Sweden

Location

Site SE46002

Uppsala, 435 33, Sweden

Location

Site TR90002

Konak, İzmir, 35020, Turkey (Türkiye)

Location

Site TR90001

Ankara, Mamak, 06620, Turkey (Türkiye)

Location

Site TR90008

Izmir, 35100, Turkey (Türkiye)

Location

Site GB44007

Corby, Northamptonshire, NN18 9EZ, United Kingdom

Location

Site GB44004

Shipley, Yorkshire, BD18 3SA, United Kingdom

Location

Site GB44002

Coventry, CV3 4FJ, United Kingdom

Location

Site GB44006

Northwood, HA6 2RN, United Kingdom

Location

Site GB44003

Orpington, BR5 3QG, United Kingdom

Location

Related Publications (1)

• Schaudig K, Wang X, Bouchard C, Hirschberg AL, Cano A, Shapiro C M M, Stute P, Wu X, Miyazaki K, Scrine L, Nappi RE. Efficacy and safety of fezolinetant for moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy: phase 3b randomised controlled trial. BMJ. 2024 Nov 18;387:e079525. doi: 10.1136/bmj-2024-079525.

  PMID: 39557487 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website.
• Link to results and other applicable study documents on the Astellas Clinical Trials website.

MeSH Terms

Interventions

fezolinetant

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 5, 2021
• Study Start: November 8, 2021
• Primary Completion: March 27, 2023
• Study Completion: April 20, 2023
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

HU (3); FI (2); DK (4); ES (4); SE (3); NL (2); DE (5); CA (11); CZ (10); NO (1); GB (5); TU (3); IT (2); FR (2); BE (1); PL (11)