Proof of Concept Study of Vaginal AZU-101 in Vulvovaginal Atrophy in Postmenopausal Women

Exclusion Criteria

• •1. 1\. Any contraindication to SERMs
• •2. High risk for breast cancer and women with ductal carcinoma in situ (DCIS)
• •3. A history of liver cancer
• •4. A history of lung cancer
• •5. Conditions resulting in an increased risk of hypercoagulability, including immobility and strong family history of hypercoagulability
• •6. Documented coronary artery disease or at increased risk for major coronary events
• •7. History of developing hypertriglyceridemia resulting from previous estrogen product treatment
• •8. History of symptomatic cataracts
• •9. History of endometrial polyps or abnormal endometrial findings on transvaginal ultrasound evaluation
• •10. 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 3 months before Screening Visit
• •3. Vaginal hormone products (rings, creams, gels) within 3 months 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 OTC medication, herbal product or nutritional supplement containing soy or plant extracts within 2 weeks prior to Screening Visit
• •11. A history or active presence of clinically important medical disease that might confound the study or be detrimental to the participant, 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
• •12. TVUS of the endometrium at Screening with a double-wall thickness measurement greater than 5 mm
• •13. A body mass index (BMI) \<18 and \>34 kg/m2
• •14. History of known alcohol or drug abuse within 1 year of the Screening Visit
• •15. Positive urine drug or alcohol screen at Screening Visit
• •16. Daily use of cigarettes or use of any electronic cigarettes
• •17. Use of an investigational drug or biologic within 60 days before administration of the first dose of study drug. Participants must agree not to participate in another research study of an investigational drug or device while enrolled in this study and for at least 30 days after completion of it.
• •18. 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; Participants with ASCUS are eligible only if high risk human papilloma virus (HPV) result is negative.
• •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 (participants 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 participant'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 \>1.5 mg/dL.
• •5. Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) \>1.5 times the ULN for the laboratory used
• •6. Fasting total cholesterol \>300 mg/dL (7.77 mmol/L) or triglycerides \>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 (participants 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. Hypotension; participants 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, hepatitis C, or active STD
• •13. Untreated vaginal or urinary tract infection, or chronic urinary tract infections requiring repeated antibiotic treatment.
• •14. Serum estradiol ≥20 pg/mL (≥73 pmol/L) at screening
• •15. Thyroid-stimulating hormone (TSH) \<0.4 or \>8.0 mIU/L
• •16. History of lichen sclerosis vulvae
• •17. Serum follicle-stimulating hormone (FSH) ≤30 IU/L
• •19. Poor venous access