Clinical trial NCT05419908: Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Official title: Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hot Flashes
Keywords: Hot flashes
ESN364
ASP2693
fezolinetant
menopause
postmenopausal
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2022-06-15
Enrollment: 87
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: 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.


Eligibility criteria: Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline to Week 12 in The Weekly General Hot Flash Score
timeFrame: Baseline and week 12
Secondary outcomes:
measure: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)
timeFrame: Baseline and weeks 4, 8 and 12
measure: Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12: 3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Estradiol (E2)
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Leptin
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Insulin
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of C-peptide
timeFrame: Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
measure: Change From Baseline in Plasma Concentration of Glycated Hemoglobin (HBA1c)
timeFrame: Baseline and week 12
measure: Number of Participants With Adverse Events (AE's)
timeFrame: From first dose of study drug until end of the study (Up to week 15)
measure: Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12
timeFrame: Baseline and week 12
measure: Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12
timeFrame: Baseline and week 12
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Site BE32004
city: Genk
country: Belgium
facility: Site BE32003
city: Gent
country: Belgium
facility: Site BE32001
city: Jette
country: Belgium
facility: Site BE32006
city: Kraainem
country: Belgium
facility: Site BE32005
city: Leuven
country: Belgium
facility: Site BE32007
city: Mons
country: Belgium
facility: Site BE32008
city: Tienen
country: Belgium
facility: Site BE32009
Study officials:
affiliation: Ogeda S.A.
name: Medical Expert
role: STUDY_DIRECTOR
References:
citation: 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.