- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02995694
A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
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 Overview
Status
Conditions
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Test
Estradiol Vaginal Cream
|
Estradiol Vaginal Cream
Other Names:
|
Active Comparator: Reference.
Estrace Vaginal Cream
|
Estrace Vaginal Cream
Other Names:
|
Placebo Comparator: Placebos
Placebo with no active pharmaceutical ingredients.
Topical vaginal cream
|
Placebo with no active pharmaceutical ingredients.
Topical vaginal cream
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vaginal Cytology
Time Frame: Day 8
|
Number of patients in PP population identified as responders at end of the study.
|
Day 8
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy
Time Frame: Day 8
|
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.
|
Day 8
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Meena Venugopal, Ph.D., Alvogen Pine Brook LLC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 71462901
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atrophic Vaginitis
-
Fayoum UniversityRecruitingAtrophic Vaginitis | Postmenopausal Atrophic VaginitisEgypt
-
Amneal Pharmaceuticals, LLCCompletedAtrophic Vaginitis Due to MenopauseUnited States
-
First Affiliated Hospital, Sun Yat-Sen UniversityUnknownAtrophic VaginitisChina
-
Wyeth is now a wholly owned subsidiary of PfizerCompletedAtrophic VaginitisUnited States
-
Actavis Inc.Teva Pharmaceuticals USACompletedAtrophic VaginitisUnited States
-
Maire Mac BrideNational Center for Advancing Translational Sciences (NCATS)TerminatedAtrophic VaginitisUnited States
-
AGUNCO Obstetrics and Gynecology CentreCompletedAtrophic VaginitisItaly
-
Wyeth is now a wholly owned subsidiary of PfizerCompletedAtrophy | Vaginitis | Atrophic VaginitisUnited States, Canada
-
Izun Pharma LtdCompletedAtrophic VaginitisIsrael, United States
-
The Cleveland ClinicFoundation for Female Health AwarenessCompletedMenopause | Atrophic VaginitisUnited States
Clinical Trials on Estradiol
-
Medical College of WisconsinTerminatedTransgenderism | Clotting DisorderUnited States
-
Teva Branded Pharmaceutical Products R&D, Inc.CompletedOral Contraceptive | HemostasisGermany, Israel, Italy, Spain
-
University of HelsinkiPäivikki and Sakari Sohlberg Foundation, Finland; Finnish Medical Foundation; Emil Aaltonen FoundationCompletedCardiovascular Disease | Postmenopausal Vasomotor SymptomsFinland
-
Mayo ClinicCompletedCardiovascular Risk ReductionUnited States
-
Novo Nordisk A/SCompletedMenopause | Postmenopausal Vaginal AtrophyGermany
-
Mahidol UniversityCompletedOvulation InhibitionThailand
-
Wake Forest University Health SciencesRecruitingRecurrent Urinary Tract InfectionUnited States
-
Oregon Health and Science UniversityCompleted
-
Novo Nordisk A/SCompletedMenopause | Postmenopausal Vaginal Atrophy
-
Peter HumaidanCompletedFrozen Embryo Transfer | Pregnancy LossDenmark