Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Condition: Hot Flashes
MeSH terms: Hot Flashes
Intervention: Fezolinetant; Placebo
Intervention description: Oral Capsule; Oral Capsule
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 87.0
Sex: Female
Minimum age: 40 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hot flashes; ESN364; ASP2693; fezolinetant; menopause; postmenopausal

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.