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

Inclusion Criteria

• Capable of providing informed consent.
• Age: 40-70 years old.
• Sex: Female
• Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Weight: At least 48 kg with all subjects having a Body Mass Index less than or equal to 38 kg/m2 but greater than or equal to 19 kg/m2.
• Baseline evaluation requirements:
• ≤5% superficial cells on vaginal smear cytology
• Vaginal pH > 5.0
• At least one patient self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy (VVA) from the following list that is identified by the subject:
• Vaginal dryness
• Vaginal and/or vulvar irritation/itching
• Dysuria
• Vaginal pain associated with sexual activity
• Vaginal bleeding associated with sexual activity (absence vs. presence)
• All subjects should be judged to be eligible for participation in this study by the principal or sub-investigator physician during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:
• a normal or non-clinically significant physical examination, including vital signs
• a normal or non-clinically significant pelvic examination that was consistent with hypoestrogenemia
• a normal or non-clinically significant breast exam and mammogram
• a normal or non-clinically significant ASCUS Papanicolaou ("Pap") smear that is negative for HPV for subjects with an intact uterus and cervix
• within normal limits or non-clinically significant laboratory evaluation results (unless otherwise noted in the exclusion criteria) for the following tests:
• Serum Chemistry
• Hematology
• Coagulogram
• Urinalysis
• normal or non-clinically significant 12- Lead ECG.
• negative urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, methadone and phencyclidine with the following exceptions: positive tests for amphetamines, barbiturates, benzodiazepines, or opiates may be allowed provided the subject has a valid prescription and is on a stable regimen that complies with Exclusion Criteria, Section 6.3.2.
• negative urine cotinine test.
• For women with an intact uterus, an endometrial thickness 50% angiographic narrowing of coronary artery, thrombosis of deep veins and arteries, thromboembolic disorders, pulmonary embolism) or history of these conditions.
• Coronary artery or cerebrovascular disease.
• Current clinically significant liver or kidney dysfunction/disorders.
• Current clinically significant gallbladder dysfunction/disorders.
• Abnormal or clinically significant breast examination. Acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
• First degree family history of breast cancer.
• Current non diet controlled diabetes mellitus or other clinically significant endocrinological disease.
• Estrogen-dependent neoplasia
• Postmenopausal uterine bleeding
• Endometrial hyperplasia
• Uncontrolled hypothyroidism
• Urinalysis showing an ongoing clinically significant urinary tract infection that requires treatment.
• Current clinically significant vaginal infection that requires treatment.
• Known chronic lichen sclerosis
• Acute illness at the time of either the pre-study medical evaluation or dosing.
• History of allergy or hypersensitivity to estradiol, other related products, or any inactive ingredients.
• Undiagnosed vaginal bleeding or history of significant risk factors for endometrial cancer.
• Increased frequency or severity of headaches while on previous hormone or estrogen therapy.
• History of psychiatric disorders occurring within the last 6 months that require hospitalization or medication.
• Current hypercalcemia, hypocalcemia, and/or hypertriglyceridemia.
• Clinically significant eye/visual ab