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

Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes

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.

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.