| Eligibility |
Inclusion Criteria:
1. Postmenopausal female subjects between 45 and 65 years old, inclusive (at the time of
signing informed consent) with at least:
1. 12 months of spontaneous amenorrhea; or
2. At least 6 weeks postsurgical bilateral oophorectomy.
2. Have self-identified at least one moderate to severe vaginal symptom that is most
bothersome to her:
1. Pain associated with sexual activity (dyspareunia)
2. Vaginal dryness
3. Vaginal irritation/itching
3. Vaginal pH =5.
4. Vaginal smear with the percentage of superficial cells not exceeding 5%
5. In the opinion of the Investigator, the subject will comply with the protocol and has
a high probability of completing the study.
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
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