A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis

Exclusion Criteria

• •* Serum Chemistry
• •* Hematology
• •* Coagulogram
• •* Urinalysis
• •6. normal or non-clinically significant 12- Lead ECG.
• •8. negative urine cotinine test.
• •8. For women with an intact uterus, an endometrial thickness \< 5 mm as determined by vaginal ultrasonography.
• •9. If warranted, other tests or examinations may be performed at the discretion of the Principal Investigator or responsible physician.
• •10. Ability to use applicator properly.
• •1. Institutionalized subjects will not be used.
• •2. Any contraindication to estrogen therapy.
• •3. Social Habits:
• •1. Use of any tobacco-containing products within 1 year of the start of the study.
• •2. Regular intake of more than 7 units of alcohol per week.
• •3. Beginning any new regimens of vitamins or herbal products within 7 days prior to the initial dose of the study medication.
• •4. Any recent, significant change in dietary or exercise habits.
• •5. History of drug and/or alcohol abuse within one year of start of study.
• •4. Medications:
• •2. Use of hormonal replacement therapies for the following time periods:
• •* within 2 weeks of baseline assessment for vaginal therapy (rings, creams, gels)
• •* within 4 weeks of baseline assessment for transdermal estrogen alone or estrogen/progestin therapy
• •* within 8 weeks of baseline assessment for oral estrogen and/or progestin therapy or intrauterine progestin therapy
• •* within 3 months of baseline assessments for progestin implants or estrogen alone injectable therapy
• •* within 6 months of baseline assessments for estrogen pellet or progestin injectable therapy
• •3. A depot injection or implant of any drug within 3 months prior to administration of study medication.
• •4. Currently taking medication indicated for anticoagulation as a result of an excluded condition listed in #5 below. This includes but is not limited to warfarin, heparin, NSAIDs, clopidogrel, dabigatran, etc.
• •5. Diseases:
• •1. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, urinary, musculoskeletal disease or malignancies unless under medical control and/or deemed not clinically significant by the Principal Investigator or Medical Sub-investigator.
• •2. Manifestation or treatment for significant cardiovascular disease (congestive heart failure, stroke or ischemic attack, myocardial infarction, coronary artery bypass, percutaneous angioplasty or \> 50% angiographic narrowing of coronary artery, thrombosis of deep veins and arteries, thromboembolic disorders, pulmonary embolism) or history of these conditions.
• •3. Coronary artery or cerebrovascular disease.
• •4. Current clinically significant liver or kidney dysfunction/disorders.
• •5. Current clinically significant gallbladder dysfunction/disorders.
• •6. Abnormal or clinically significant breast examination. Acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
• •7. First degree family history of breast cancer.
• •8. Current non diet controlled diabetes mellitus or other clinically significant endocrinological disease.
• •9. Estrogen-dependent neoplasia
• •10. Postmenopausal uterine bleeding
• •11. Endometrial hyperplasia
• •12. Uncontrolled hypothyroidism
• •13. Urinalysis showing an ongoing clinically significant urinary tract infection that requires treatment.
• •14. Current clinically significant vaginal infection that requires treatment.
• •15. Known chronic lichen sclerosis
• •16. Acute illness at the time of either the pre-study medical evaluation or dosing.
• •17. History of allergy or hypersensitivity to estradiol, other related products, or any inactive ingredients.
• •18. Undiagnosed vaginal bleeding or history of significant risk factors for endometrial cancer.
• •19. Increased frequency or severity of headaches while on previous hormone or estrogen therapy.
• •20. History of psychiatric disorders occurring within the last 6 months that require hospitalization or medication.
• •21. Current hypercalcemia, hypocalcemia, and/or hypertriglyceridemia.
• •22. Clinically significant eye/visual abnormalities such as retinal vascular thrombosis, partial or complete loss of vision, proptosis, diplopia, papilledema, retinal vascular lesions.
• •6. Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study.
• •7. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
• •8. Sitting blood pressure higher than 150/90 mmHg at screening.
• •9. Baseline serum estradiol levels \>30 pg/mL at screening.