Open-Label Study of Vaginal AZU-101 in Postmenopausal Women

Exclusion Criteria

• •1. Any contraindication to SERMs
• •2. Use of any of the following:
• •1. Oral estrogen-, progestin-, androgen-, or SERM-containing drug products within 3 months before Screening Visit
• •2. Transdermal hormone products within 4 weeks before Screening Visit
• •3. Vaginal hormone products (rings, creams, gels) within 4 weeks before Screening Visit
• •4. Intrauterine progestins within 8 weeks before Screening Visit
• •5. Progestin implants/injectables or estrogen pellets/injectables within 6 months before Screening Visit
• •6. Any medication, herbal product or nutritional supplement known or suspected to interact with AZU-101 within 2 weeks prior to Screening Visit
• •3. Evidence of underlying disease during the Screening Visit (performed within 28 days of Day 1) or at admission on Day 1.
• •4. A history or active presence of clinically important medical disease that might confound the study or be detrimental to the subject, including but not limited to:
• •1. Endometrial hyperplasia
• •2. Undiagnosed vaginal bleeding
• •3. History of a chronic liver or kidney dysfunction/disorder (e.g., hepatitis C or chronic renal failure)
• •4. Thrombophlebitis, thrombosis, or thromboembolic disorders
• •5. Cerebrovascular accident, stroke, or transient ischemic attack
• •6. Myocardial infarction or ischemic heart disease
• •7. Malignancy or treatment for malignancy, within the previous 5 years, with the exception of basal cell carcinoma of the skin or squamous cell carcinoma of the skin
• •8. History of estrogen dependent neoplasia, breast cancer, melanoma, or any gynecologic cancer, at any time
• •9. Endocrine disease (except for controlled hypothyroidism or controlled non-insulin dependent diabetes mellitus)
• •10. Known breast cancer gene (BRCA) mutation associated with increased risk of neoplasia
• •5. TVUS of the endometrium at Screening with a double-wall thickness measurement greater than 4 mm
• •6. Abnormal endometrial biopsy in non-hysterectomized women
• •7. A body mass index (BMI) \<18 and \>38 kg/m2
• •8. History of known alcohol or drug abuse within 1 year of the Screening Visit
• •9. Positive urine drug or alcohol screen at Screening Visit
• •10. Use of 15 or more cigarettes per day or current use of any electronic cigarettes
• •11. Use of an investigational drug or biologic within 60 days before administration of the first dose of study drug
• •12. Any clinically important abnormalities on Screening physical examination, assessments, ECG, or laboratory tests, including but not limited to:
• •1. Unresolved cervical cytologic smear report of atypical glandular cells of undetermined significance (AGUS) or atypical squamous cells of undetermined significance (ASCUS). Cervical cytologic smear report of low-grade squamous intraepithelial lesion (SIL) or greater, cervical intraepithelial neoplasia (CIN) grade 1 or greater, or any reported dysplasia; Subjects with ASCUS are eligible only if high risk human papilloma virus (HPV) result is negative or she has a history of vaccination against HPV.
• •2. Unresolved findings suspicious for malignancy on the breast exam; incomplete mammogram result (Breast Imaging Reporting and Data System \[BI-RADS\] category 0) or unresolved findings suggestive of malignant changes or findings requiring short interval follow-up on the pre-study mammogram (subjects must have mammography result of BI-RADS category 1 or 2 to enroll). Mammogram performed within 9 months prior to Screening Visit with documentation available may be used to evaluate study eligibility. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment.
• •3. Hematocrit \<35% or \>45%
• •4. Serum creatinine \>15% of the upper limit of normal (ULN) for the laboratory used.
• •5. Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) \>1.5 times the ULN for the laboratory used
• •6. Fasting total cholesterol greater than 300 mg/dL (7.77 mmol/L) or triglycerides greater than 300 mg/dL (3.39 mmol/L)
• •7. Positive laboratory finding for Factor V Leiden mutation
• •8. Fasting glucose \>125 mg/dL
• •9. Uncontrolled hypertension (subjects with sitting BP \>139 mmHg systolic or \>89 mmHg diastolic) and may not be using more than 2 antihypertensive medications for the treatment of hypertension
• •10. Uncontrolled hypotension; subjects with sitting BP \<95 mmHg systolic or \<65 mmHg diastolic
• •11. A clinically significant abnormal 12-lead ECG (e.g., showing previous myocardial infarction or other findings suggestive of ischemia)
• •12. Positive human immunodeficiency virus (HIV), hepatitis B, or hepatitis C