A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
Primary Purpose
Atrophic Vaginitis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Estradiol
Placebos
Reference
Sponsored by
About this trial
This is an interventional other trial for Atrophic Vaginitis
Eligibility Criteria
Inclusion Criteria:
- Signed Informed Consent that meets all criteria of current FDA regulations
- Females age: 30-75 years old inclusive who are postmenopausal.
- 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.
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.
- Normal breast exam at screening and mammogram completed within 9 months prior to screening in patients >40 years old.
- For women with an intact uterus, an endometrial thickness < 4 mm as determined by vaginal ultrasonography.
- 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:
- Females younger than 30 years of age or older than 75 years of age
- Patients with a serum FSH level of ≤ 40mIU/ml at screening.
- Greater than 5% superficial cells on vaginal cytology.
- Vaginal pH ≤ 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.
- 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.
- 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.
- Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure > 90 mm Hg
- Any patient with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
- Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Test
Reference.
Placebos
Arm Description
Estradiol Vaginal Cream
Estrace Vaginal Cream
Placebo with no active pharmaceutical ingredients. Topical vaginal cream
Outcomes
Primary Outcome Measures
Vaginal Cytology
Number of patients in PP population identified as responders at end of the study.
Secondary Outcome Measures
Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy
Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A "Treatment Success" was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Full Information
NCT ID
NCT02995694
First Posted
December 14, 2016
Last Updated
November 30, 2021
Sponsor
Alvogen Pine Brook LLC
1. Study Identification
Unique Protocol Identification Number
NCT02995694
Brief Title
A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
Official Title
Clinical Endpoint Therapeutic Equivalence Multi-Site Study Comparing Estradiol Vaginal Cream (0.01%; Alvogen Pine Brook LLC.) to Estrace® Cream (0.01%; Warner Chilcott) in Postmenopausal Females With Atrophic Vaginitis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alvogen Pine Brook LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed Description
This randomized, double-blind, placebo-controlled, parallel group, multiple-site study was designed to evaluate the therapeutic efficacy and safety of a generic Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC) compared to the FDA Reference Listed Drug (RLD), Estrace® (estradiol vaginal cream USP, 0.01%, Warner Chilcott) in patients with atrophic vaginitis. Additionally, both the Test and the RLD formulations were tested for superiority against a Placebo.
Following the 14-day screening period, patients who continued to meet the inclusion/exclusion criteria were randomized in a 2:2:1 ratio (Test: Reference: Placebo) for 7 days of treatment.
Five hundred and thirty-five (535) patients were randomized to one of the three study products as follows:
Test: Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC)
Reference: Estrace® (estradiol vaginal cream USP, 0.01%) (Warner Chilcott)
Placebo: Test product vehicle cream (Alvogen Pine Brook LLC)
Patients completed up to three clinic visits as follows:
Visit 1 - Screening: Day -14 to Day -1
Visit 2 - Randomization: Day 1
Visit 3 - End of Study: Day 8, maximum Day 10
Study product was self-administered by the patient for 7 days according to the dosing instructions provided. Each patient was required to dose once daily at approximately the me of day for 7 consecutive days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrophic Vaginitis
7. Study Design
Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
535 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Test
Arm Type
Experimental
Arm Description
Estradiol Vaginal Cream
Arm Title
Reference.
Arm Type
Active Comparator
Arm Description
Estrace Vaginal Cream
Arm Title
Placebos
Arm Type
Placebo Comparator
Arm Description
Placebo with no active pharmaceutical ingredients. Topical vaginal cream
Intervention Type
Drug
Intervention Name(s)
Estradiol
Other Intervention Name(s)
Estadiol Vaginal Cream
Intervention Description
Estradiol Vaginal Cream
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
Topical Vaginal Cream
Intervention Description
Placebo with no active pharmaceutical ingredients. Topical vaginal cream
Intervention Type
Drug
Intervention Name(s)
Reference
Other Intervention Name(s)
Topical Vaginal Cream
Intervention Description
Estrace Vaginal Cream
Primary Outcome Measure Information:
Title
Vaginal Cytology
Description
Number of patients in PP population identified as responders at end of the study.
Time Frame
Day 8
Secondary Outcome Measure Information:
Title
Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy
Description
Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A "Treatment Success" was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Time Frame
Day 8
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed Informed Consent that meets all criteria of current FDA regulations
Females age: 30-75 years old inclusive who are postmenopausal.
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.
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.
Normal breast exam at screening and mammogram completed within 9 months prior to screening in patients >40 years old.
For women with an intact uterus, an endometrial thickness < 4 mm as determined by vaginal ultrasonography.
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:
Females younger than 30 years of age or older than 75 years of age
Patients with a serum FSH level of ≤ 40mIU/ml at screening.
Greater than 5% superficial cells on vaginal cytology.
Vaginal pH ≤ 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.
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.
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.
Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure > 90 mm Hg
Any patient with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meena Venugopal, Ph.D.
Organizational Affiliation
Alvogen Pine Brook LLC
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
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