Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

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ultrasound to assess endometrial thickness at Screening and at Week 12 (end-of-treatment, - and subjects) who are withdrawn from the study prior to completion, at the Early Termination (ET) Visit.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mm) and at Week 12 (end--of--treatment) - all subjects), for subjects with uterine bleeding, and for subjects who are withdrawn from the study prior to completion, at the ET Visit if study drug exposure is ≥10 weeks.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.

Exclusion Criteria:

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;
Exclusion criterion 7 has been removed in Amendment 1;
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;
Unable or unwilling to complete the study procedures; or
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.