A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
Condition: Atrophic Vaginitis
MeSH terms: Vaginitis; Atrophic Vaginitis; Atrophy
Intervention: Estradiol; Placebos; Reference
Intervention description: Estradiol Vaginal Cream; Placebo with no active pharmaceutical ingredients. Topical vaginal cream; Estrace Vaginal Cream
Intervention MeSH terms: Estradiol
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 535.0
Sex: Female
Minimum age: 30 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the therapeutic equivalence of Alvogen's estradiol
      vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol
      describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7
      day treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Informed Consent that meets all criteria of current FDA regulations

          2. Females age: 30-75 years old inclusive who are postmenopausal.

          3. 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. Hysterectomy without
             oophorectomy if of age that investigator believes would have naturally reached 12
             months of spontaneous amenorrhea.

          4. 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)*
                  *provided that patient is currently sexually active and plans to remain so
                  throughout study.

          5. Normal breast exam at screening and mammogram completed within 9 months prior to
             screening in patients >40 years old.

          6. For women with an intact uterus, an endometrial thickness < 4 mm as determined by
             vaginal ultrasonography.

          7. Documented PAP smear conducted within previous 12 months with no findings that the
             Investigator believes would contraindicate the use of topical vaginal estradiol

        Exclusion Criteria:

          1. Females younger than 30 years of age or older than 75 years of age

          2. Patients with a serum FSH level of ≤ 40mIU/ml at screening.

          3. Greater than 5% superficial cells on vaginal cytology.

          4. Vaginal pH ≤ 5

          5. Significant history or current evidence of chronic infectious disease, system
             disorder, organ disorder (including significant liver/kidney impairment) or other
             medical condition that in the Investigator's opinion would place the study patient at
             undue risk by participation or could jeopardize the integrity of the study
             evaluations.

          6. Patients with an intact uterus should have vaginal ultrasonography results to confirm
             an inactive endometrial lining. Patients with an endometrial thickness equal to or
             greater than 4mm should be excluded.

          7. Patients with known, suspected or current history of carcinoma of the breast. All
             patients over the age of 40 must have had a mammogram performed within 9 months of the
             study start and all patients will have a physical breast exam performed at screening.

          8. Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure
             > 90 mm Hg

          9. Any patient with undiagnosed vaginal bleeding or significant risk factors for
             endometrial cancer.

         10. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).