Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes

NCT05419908 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ESN364_HF_2042015-002578-20
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 8

Brief Summary

The primary purpose of this study was to evaluate the effect of ESN364 on the severity and frequency of hot flashes in early postmenopausal women suffering from hot flashes, in terms of changes in weekly Hot Flash Score from baseline to Week 12. This study also evaluated the effect of ESN364 on the severity and frequency of hot flashes at additional timepoints; hot flash interference on daily life, in terms of changes from baseline over time in Hot Flash Related Daily Interference Scale (HFRDIS); the effect of ESN364 on climacteric symptoms, in terms of changes from baseline over time in Leeds Sleep Evaluation Questionnaire (LSEQ), Greene Climacteric Scale (GCS), and Sheehan Disability Scale (SDS); pharmacodynamic (PD) effect; and safety and tolerability.

Conditions

Hot Flashes

Keywords

Hot flashes; ESN364; ASP2693; fezolinetant; menopause; postmenopausal

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in The Weekly General Hot Flash Score

  The HF score (based on severity and frequency) was calculated as: (number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3) The severity of HFs is clinically defined as follows: * Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing. * Moderate: 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: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed). Higher scores indicate worse symptoms. There is no maximum score since the score was participant dependent for both number and severity.

  Baseline and week 12

Secondary Outcomes (25)

• Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)

  Baseline and weeks 4, 8 and 12

• Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)

  Baseline and weeks 4, 8 and 12

• Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12

  Baseline and weeks 4, 8 and 12

• Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

  Baseline and weeks 4, 8 and 12

• Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

  Baseline and weeks 4, 8 and 12

Study Arms (2)

Fezolinetant

EXPERIMENTAL

Participants received 90 milligrams (mg) fezolinetant capsules orally, twice daily (BID) for a period of 12 weeks

Drug: Fezolinetant

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Fezolinetant DRUG

Oral Capsule

Also known as: ESN364, ASP2693

Fezolinetant

Placebo DRUG

Oral Capsule

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:

• Spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (FSH \>40 IU/L); or spontaneous amenorrhea for at least 3 months with biochemical/physical criteria of menopause (FSH \>40 IU/L and E2 \<0.21 nmol/); or having had bilateral oophorectomy at least 6 weeks prior to screening (with or without hysterectomy);
• At least 49 moderate or severe hot flashes or night sweats over a period of 7 consecutive days, as recorded in the daily diary during the screening period, with at least 4 of those days with 7 or more moderate or severe hot flashes per day;
• In good general health as determined on the basis of medical history and general physical examination performed at screening; hematology and chemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range for the population studied, or showing no clinically relevant deviations;
• Negative urine test for selected drugs of abuse (amphetamines, tricyclic antidepressants, cannabinoids, cocaine, tetrahydrocannabinol, or opiates) at screening;
• Negative serology panel (including hepatitis B surface antigen \[HBsAg\], antihepatitis C virus \[HCV\] and human immunodeficiency virus (HIV) antibody screens);
• Negative urine pregnancy test at screening;

You may not qualify if:

• Use of a prohibited therapy or not willing to wash-out drugs considered prohibited therapies;
• History (in the past year) or presence of drug or alcohol abuse;
• Suicide attempt in the past 3 years;
• Previous or current history of a malignant tumor (except basal cell carcinoma);
• Active liver disease or jaundice, or out-of-range values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); or total bilirubin \>1.3 times the upper limit of normal (ULN); or creatinine \>1.5 times the ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula \<60 mL/min/1.73 m2 at screening;
• Medical condition or chronic disease (including history of neurological \[including cognitive\], hepatic, renal, cardiovascular, gastrointestinal, pulmonary \[e.g., moderate asthma\], or endocrine disease) or malignancy that could confound interpretation of the study outcome;
• Any psychological disorder according to the criteria indicated in the Diagnostics and Statistical Manual of Mental Disorders (DSM, 4th edition) within one year prior to screening. Such disorders include but are not limited to current major depression, alcohol (more than 3 glasses of wine, beer, or equivalent/day) or substance abuse/dependence;
• Unsuited to participate in the study, based on findings observed during physical examination, vital sign assessment, or 12-lead ECG;
• History of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;
• Presence or sequellae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution, metabolism, or excretion (ADME) mechanisms of drugs;
• Concurrent participation in another interventional study (or participation within 3 months prior to screening in this study);
• History of poor compliance in clinical studies;
• Unable or unwilling to complete the study procedures;
• Subject is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof who is directly involved in the conduct of the study.

Sponsors & Collaborators

• Ogeda S.A.: lead

Study Sites (8)

Site BE32004

Brussels, 1000, Belgium

Location

Site BE32003

Genk, 3600, Belgium

Location

Site BE32001

Ghent, 9000, Belgium

Location

Site BE32006

Jette, 1090, Belgium

Location

Site BE32005

Kraainem, 1950, Belgium

Location

Site BE32007

Leuven, Belgium

Location

Site BE32008

Mons, 7000, Belgium

Location

Site BE32009

Tienen, 3300, Belgium

Location

Related Publications (1)

• Depypere H, Timmerman D, Donders G, Sieprath P, Ramael S, Combalbert J, Hoveyda HR, Fraser GL. Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial. J Clin Endocrinol Metab. 2019 Dec 1;104(12):5893-5905. doi: 10.1210/jc.2019-00677.

  PMID: 31415087 RESULT

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 Expert

  Ogeda S.A.

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 15, 2022
• Study Start: September 21, 2015
• Primary Completion: September 21, 2016
• Study Completion: October 6, 2016
• Last Updated: November 27, 2024
• Results First Posted: July 25, 2023

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (8)