Table 1.

Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Born female, aged ≥ 40 years and ≤ 65 years at screening	Receiving strong or moderate cytochrome P450 1A2 (CYP1A2) inhibitors, hormone replacement therapy, hormonal contraceptive, or any treatment for VMS (prescription, OTC, or herbal)
BMI ≥ 18 kg/m2 and ≤ 38 kg/m2	Previous/current history of a malignant tumor, except for basal cell carcinoma
Seeking treatment/relief for VMS associated with menopause and at the screening visit having: Spontaneous amenorrhea for ≥ 12 consecutive months; Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (FSH > 40 IU/L); or Had bilateral oophorectomy ≥ 6 weeks prior to the screening visit	SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg based on an average of 2–3 readings on at least 2 different occasions within the screening period Women who did not meet these criteria may, at the discretion of the investigator, be reassessed after initiation or review of antihypertensive measures Women with a medical history of hypertension could be enrolled at the discretion of the investigator once they are medically clear (stable and compliant)
Within 10 days prior to randomization, must have a minimum average of 7–8 moderate to severe VMS/day, or 50–60/week	History within the last 6 months of undiagnosed uterine bleeding
Normal/negative or no clinically significant findings on mammogram within the previous 12 months or at screening	A medical condition or chronic disease (including history of neurological, hepatic, renal, CV, GI, pulmonary [eg, moderate asthma], endocrine or gynecological disease) or malignancy that could confound interpretation of the study
Normal or not clinically significant Pap test result within the previous 12 months or at screening	Active liver disease, jaundice, or elevated liver aminotransferases (ALT or AST), elevated total or direct bilirubin, elevated INR, or elevated alkaline phosphatase. Participants with mildly elevated ALT or AST up to 1.5 times ULN could be enrolled if total and direct bilirubin were normal. Participants with mildly elevated alkaline phosphatase (up to 1.5 times ULN) could be enrolled if cholestatic liver disease was excluded and no cause other than fatty liver was diagnosed. Participants with Gilbert's syndrome with elevated total bilirubin could be enrolled as long as direct bilirubin, hemoglobin, and reticulocytes were normal
Willing to undergo a transvaginal ultrasound to evaluate the uterus and ovaries at screening and at week 52 (EOT), and at early discontinuation for women who withdraw from the study prior to completion	Creatinine >1.5 times ULN; or estimated glomerular filtration rate ≤59 mL/min per 1.73 m2 at screening
Willing to undergo an endometrial biopsy at screening and at week 52 (EOT) unless she has had a supracervical or full hysterectomy. The endometrial biopsy obtained at screening must be considered evaluable. In addition, willing to undergo endometrial biopsy in the event of uterine bleeding or early discontinuation of the study or study drug

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CV, cardiovascular; CYP1A2, cytochrome P450 1A2; DBP, diastolic blood pressure; EOT, end of treatment; FSH, follicle-stimulating hormone; GI, gastrointestinal; INR, international normalized ratio; OTC, over the counter; Pap, Papanicolaou; SBP, systolic blood pressure; ULN, upper limit of normal; VMS, vasomotor symptoms.