A Dose-ranging Study of the Efficacy of ESN364 in Postmenopausal Women Suffering Vasomotor Symptoms (Hot Flashes)

NCT03192176 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ESN364_HF_205
• Study Type: interventional
• Target: 356
• Locations: 1 country
• Sites: 51

Brief Summary

This study determined the effects of different doses and dosing regimens of ESN364 on the frequency and severity of hot flashes. The treatment was administered for 12 weeks to postmenopausal women, aged 40 to 65, suffering at least 50 moderate to severe hot flashes per week.

Conditions

Menopause; Hot Flashes

Keywords

Vasomotor symptoms; Menopause; Hot flashes; Perimenopause

Outcome Measures

Primary Outcomes (4)

• Co-Primary Efficacy Endpoint: Change From Baseline (CFB) in The Mean Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Week 4

  The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

  Baseline and week 4

• Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12

  The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency and severity per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

  Baseline and week 12

• Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4

  Severity of moderate to severe VMS per day was calculated as follows: \[(number of moderate VMS × 2) + (number of severe VMS × 3)\]/number of daily moderate/severe VMS. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no moderate or severe VMS. Higher score indicates greater severity.

  Baseline and week 4

• Co-Primary Efficacy Endpoint: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12

  Severity of moderate to severe VMS per day was calculated as follows: \[(number of moderate VMS × 2) + (number of severe VMS × 3)\]/number of daily moderate/severe VMS. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no moderate or severe VMS. Higher scores indicates greater severity.

  Baseline and week 12

Secondary Outcomes (32)

• Change From Baseline in The Mean Frequency of Mild, Moderate, and Severe VMS to Each Study Week

  Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

• Change From Baseline in The Mean Frequency of Moderate and Severe VMS to Each Study Week

  Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15

• Change From Baseline in The Mean Severity of Mild, Moderate, and Severe VMS to Each Study Week

  Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

• Change From Baseline in The Mean Severity of Moderate and Severe VMS to Each Study Week

  Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15

• Change From Baseline in The Hot Flash Score of Mild, Moderate, and Severe VMS to Each Study Week

  Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Study Arms (8)

Placebo

PLACEBO COMPARATOR

Participants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 15 mg

EXPERIMENTAL

Participants received fezolinetant 15 mg capsules orally, BID for a period of 12 weeks.

Drug: Placebo

Fezolinetant 30 mg

EXPERIMENTAL

Participants received fezolinetant 30 mg capsules orally, BID for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 60 mg

EXPERIMENTAL

Participants received fezolinetant 60 mg capsules orally, BID for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 90 mg

EXPERIMENTAL

Participants received fezolinetant 90 mg capsules orally, BID for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 30 mg + Placebo

EXPERIMENTAL

Participants received fezolinetant 30 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 60 mg + Placebo

EXPERIMENTAL

Participants received fezolinetant 60 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.

Drug: Fezolinetant

Fezolinetant 120 mg + Placebo

EXPERIMENTAL

Participants received fezolinetant 120 mg capsules orally, QD and matching placebo QD for a period of 12 weeks.

Drug: Fezolinetant

Interventions

Fezolinetant DRUG

Oral Capsule

Also known as: ESN364

Fezolinetant 120 mg + Placebo; Fezolinetant 30 mg; Fezolinetant 30 mg + Placebo; Fezolinetant 60 mg; Fezolinetant 60 mg + Placebo; Fezolinetant 90 mg; Placebo

Placebo DRUG

Oral Capsule

Fezolinetant 15 mg

Eligibility Criteria

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

You may qualify if:

• Women \>40 years and ≤65 years of age at the screening visit;
• A body mass index between 18 kg/sqm to 38 kg/sqm (extremes included);
• Spontaneous amenorrhea for ≥12 consecutive months; or spontaneous amenorrhea for ≥6 months with biochemical criteria of menopause (follicle-stimulating hormone \[FSH\] \>40 IU/L); or having had bilateral oophorectomy ≥6 weeks prior to the screening visit (with or without hysterectomy);
• At least 50 moderate to severe vasomotor symptoms per week (ie, 7 consecutive days), as recorded in the daily diary during the screening period;
• In good general health as determined on the basis of medical history and general physical examination, including a bimanual clinical pelvic examination and clinical breast examination devoid of relevant clinical findings, performed at the screening visit; hematology and biochemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range for the population studied, or showing no clinically relevant deviations, as judged by the Investigator;
• Women \>40 years of age who have documentation of a normal/negative or no clinically significant findings mammogram (obtained at Screening or within the prior 9 months of trial enrollment.) Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic findings;
• Willing to undergo a transvaginal ultrasound to assess endometrial thickness at Screening and at Week 12 (end-of-treatment, - and subjects) who are withdrawn from the study prior to completion, at the Early Termination (ET) Visit. This is not required for subjects who have had a partial (supracervical) or full hysterectomy;
• Willing to undergo an endometrial biopsy at Screening (in the event that the subject's transvaginal ultrasound shows endometrial thickness ≥4 mm) and at Week 12 (end--of--treatment) - all subjects), for subjects with uterine bleeding, and for subjects who are withdrawn from the study prior to completion, at the ET Visit if study drug exposure is ≥10 weeks. This is not required for subjects who have had a partial (supracervical) or full hysterectomy;
• Negative alcohol breath test and negative urine test for selected drugs of abuse (amphetamines, tricyclic antidepressants, cocaine, or opiates) at the screening visit;
• Negative urine pregnancy test;
• Negative serology panel (including hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody screens);
• Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; and
• Documentation of a normal Pap smear (or equivalent cervical cytology) or of no clinical significance in the opinion of the Investigator within the previous 9 months or at Screening.

You may not qualify if:

• Use of a prohibited therapy (hormone therapy, hormonal contraceptive, or vasomotor symptom medication \[prescription, over the counter, or herbal\]) or not willing to wash out drugs
• History (in the past year) or presence of drug or alcohol abuse;
• Previous or current history of a malignant tumor, except for basal cell carcinoma;
• Uncontrolled hypertension and a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg;
• Judged by the Investigator to be unsuited to participate in the study based on findings observed during physical examination, vital sign assessment, or 12-lead electrocardiogram (ECG);
• History of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;
• An unacceptable result from endometrial biopsy (performed when endometrial thickness is ≥ 4mm measured by transvaginal ultrasound) of endometrial hyperplasia, endometrial cancer, or inadequate specimen at Screening (1 repeat biopsy permitted if technically possible);
• History of endometrial hyperplasia or uterine/endometrial cancer;
• History of unexplained uterine bleeding;
• History of seizures or other convulsive disorders;
• Medical condition or chronic disease (including history of neurological \[including cognitive\], hepatic, renal, cardiovascular, gastrointestinal, pulmonary \[eg, moderate asthma\], endocrine, or gynecological disease) or malignancy that could confound interpretation of the study outcome;
• Presence or sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion (ADME) mechanisms of drugs as judged by the Investigator;
• Active liver disease or jaundice, or values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>1.5 x the upper limit of normal (ULN); or total bilirubin \>1.5 x ULN; or creatinine \>1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula ≤59 mL/min/1.73 sqm at the screening visit;
• Concurrent participation in another interventional study (or participation within 3 months prior to screening in this study);
• Suicide attempt in the past 3 years;

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (51)

Research Site

Anniston, Alabama, 36207, United States

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Birmingham, Alabama, 35205, United States

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Phoenix, Arizona, 85023, United States

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Los Angeles, California, 90057, United States

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Oceanside, California, 92056, United States

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Panorama City, California, 91402, United States

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Research Site 052

Sacramento, California, 95821, United States

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Sacramento, California, 95821, United States

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San Diego, California, 92114, United States

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Thousand Oaks, California, 91360, United States

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Valley Village, California, 91607, United States

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Denver, Colorado, 80209, United States

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Milford, Connecticut, 06460, United States

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Crystal River, Florida, 34429, United States

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DeLand, Florida, 32720, United States

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Jupiter, Florida, 33458, United States

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Lake Worth, Florida, 33461, United States

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Miami, Florida, 33144, United States

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Ormond Beach, Florida, 32174, United States

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Port Saint Lucie, Florida, 34952, United States

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Atlanta, Georgia, 30312, United States

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Norcross, Georgia, 30092, United States

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Meridian, Idaho, 83642, United States

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Champaign, Illinois, 61820, United States

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Marrero, Louisiana, 70072, United States

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Elkridge, Maryland, 21075, United States

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Watertown, Massachusetts, 02472, United States

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Lincoln, Nebraska, 68510, United States

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Norfolk, Nebraska, 68701, United States

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Las Vegas, Nevada, 89123, United States

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New York, New York, 10032, United States

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Williamsville, New York, 14221, United States

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Cincinnati, Ohio, 45267, United States

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Cleveland, Ohio, 44122, United States

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Columbus, Ohio, 43210, United States

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Columbus, Ohio, 43213, United States

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Oklahoma City, Oklahoma, 73112, United States

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Philadelphia, Pennsylvania, 19140, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Clarksville, Tennessee, 37040, United States

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Kingsport, Tennessee, 37660, United States

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Houston, Texas, 77058, United States

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Hurst, Texas, 76054, United States

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Lampasas, Texas, 76550, United States

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Plano, Texas, 75093, United States

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San Antonio, Texas, 78229, United States

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Riverton, Utah, 84065, United States

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Charlottesville, Virginia, 22911, United States

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Vienna, Virginia, 22182, United States

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Seattle, Washington, 98105, United States

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Spokane, Washington, 99207, United States

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Related Publications (1)

• Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N, Lee M, Skillern L, Ramael S. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020 Apr;27(4):382-392. doi: 10.1097/GME.0000000000001510.

  PMID: 32102086 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website.

MeSH Terms

Conditions

Hot Flashes

Interventions

fezolinetant

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: July 19, 2017
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: November 26, 2024
• Results First Posted: September 29, 2021

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (51)