Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, 10 mcg and Vagifem® 10 mcg and Compare to Placebo

NCT ID: NCT01779947

Last Updated: 2014-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

519 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-31

Study Completion Date

2012-12-31

Brief Summary

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The purpose of this study is to compare the safety and efficacy of generic Estradiol Vaginal Inserts, USP 10 mcg to the reference product Vagifem® 10 mcg and to determined whether the efficacy of each of the 2 active treatments is superior to that of the placebo.

Detailed Description

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Conditions

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Atrophic Vaginitis Due to Menopause

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Estradiol Vaginal Insert 10 mcg

Estradiol Vaginal Insert 10 mcg - Test Product

Group Type EXPERIMENTAL

Estradiol Vaginal Tablets 10 mcg

Intervention Type DRUG

Vagifem Tablets 10 mcg

Vagifem® (Estradiol Vaginal Tablets) 10 mcg - Reference Listed Drug

Group Type ACTIVE_COMPARATOR

Estradiol Vaginal Tablets 10 mcg

Intervention Type DRUG

Placebo

Placebo for the test product Estradiol Vaginal Tablets 10 mcg

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Interventions

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Estradiol Vaginal Tablets 10 mcg

Intervention Type DRUG

placebo

Intervention Type DRUG

Other Intervention Names

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Vagifem®

Eligibility Criteria

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Inclusion Criteria

* Willing and able to provide and understand written informed consent for the study.
* Healthy female subject aged 30 to 75 years, inclusive, who was postmenopausal, defined as having had 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
* At least 1 subject-assessed moderate to severe symptom of VVA among the following 4 symptoms that was identified by the subject as being most bothersome to her:
* Vaginal dryness
* Vaginal and/or vulvar irritation/itching
* Dysuria
* Vaginal pain associated with sexual activity OR
* The presence of vaginal bleeding associated with sexual activity
* Had ≤ 5% superficial cells on vaginal smear cytology at Visit 1.
* Vaginal pH \> 5.0 at Visit 1.
* Systolic blood pressure ≤ 150 mm Hg and diastolic blood pressure ≤ 90 mm Hg at Visit 1.
* If \> 40 years old, documentation of a negative mammogram (obtained at Visit 1 or within 9 months prior to Visit 1). A radiology report documenting a negative mammogram must have been available and must have been taken within 9 months of Visit 1 or obtained at Visit 1.
* Normal clinical breast examination at Visit 1.
* For women with intact uterus, vaginal ultrasonography confirmation at Visit 1 of an inactive endometrial lining, with an endometrial thickness \< 4 mm.
* Documented Pap smear conducted within the previous 12 months of Visit 1 with no findings that the investigator believed would contraindicate the use of topical vaginal estradiol.
* In general good health with no clinically significant disease other than symptoms of VVA that might have interfered with the study evaluations.
* Was willing and able to understand and comply with the requirements of the study, including applying the medication as instructed, returning for the required study visits, complying with therapy prohibitions, and able to complete the study.

Exclusion Criteria

* Known hypersensitivity to estradiol vaginal tablet or any component of the study medication.
* A subject who had received any treatment listed below more recently than the indicated washout period prior to Visit 1/Screening/Baseline.
* Prohibited Medications - (Washout Period Prior to Visit 1/Screening/Baseline)
* Vaginal lubricants or moisturizers - (at least 48 hours (2 days))
* Vaginal hormonal products (rings, creams, gels) - (at least 1 week (7 days))
* Transdermal estrogen alone or estrogen/progestin products - (at least 4 weeks (28 days))
* Oral estrogen and/or progestin therapy - (at least 8 weeks (56 days))
* Intrauterine progestin therapy - (at least 8 weeks (56 days))
* Progestin implants and estrogen alone injectable drug therapy - (at least 3 months (90 days))
* Estrogen pellet therapy or progestin injectable drug therapy - (at least 6 months (180 days))
* Subject who had engaged in sexual intercourse within 48 hours (2 days) of Visit 1.
* Screening mammogram or clinical breast examination results indicating any suspicion of breast malignancy.
* History of undiagnosed vaginal bleeding.
* Known bleeding disorder.
* History of significant risk factors for endometrial cancer (i.e., tamoxifen use, prior pelvic radiation therapy, and endometrial hyperplasia).
* For women with an intact uterus, screening vaginal ultrasonography showing endometrial thickness of ≥ 4 mm.
* Known, suspected, or history of breast cancer or cervical cancer.
* Known or suspected estrogen-dependent neoplasia.
* History of uncontrolled hypertension.
* Active deep vein thrombosis, pulmonary embolism, or history of these conditions.
* Active arterial thromboembolic disease (e.g., stroke or myocardial infarction) or a history of these conditions.
* Known liver dysfunction or disease.
* Known anaphylactic reaction or angioedema to estradiol vaginal tablets.
* Known protein C, protein S, antithrombin deficient, or other known thrombophilic disorders. - Active vaginal herpes simplex infection or any known concurrent vaginal infections.
* Abnormal Pap smear within the previous 12 months of Visit 1 or obtained during Visit 1. Any evidence of malignancy or premalignant changes or atypical squamous cell of undetermined significance (ASCUS) Pap smear with positive high risk human papillomavirus (HPV).
* Any clinically significant condition or situation (including laboratory values) other than the condition being studied that, in the opinion of the investigator, would have interfered with the study evaluations or optimal participation in the study.
* Use of any investigational drugs or device within 30 days of signing the ICF.
* Current participation in any other clinical study involving an investigational drug or device.
* Consumed excessive amounts of alcohol, abused drugs, or had any condition that would have compromised compliance with this protocol.
* Previous participation in this study.
* Subjects who, in the opinion of the Investigator, would have been non-compliant with the requirements of the study protocol.
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amneal Pharmaceuticals, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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W. Todd Kays, PhD

Role: STUDY_CHAIR

Amneal Pharmaceuticals, LLC

Locations

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Medical Affiliated Research center, Inc.

Huntsville, Alabama, United States

Site Status

Montogmery Women's Health Associates

Montgomery, Alabama, United States

Site Status

Medical Center for Clinical Research

San Diego, California, United States

Site Status

Women's Health Care Research Corp.

San Diego, California, United States

Site Status

Downtown Women's Health care

Denver, Colorado, United States

Site Status

Horizons Clinical Research Center

Denver, Colorado, United States

Site Status

James A. Simon, MD PC/ Women's Health and Research Consultants

Washington D.C., District of Columbia, United States

Site Status

Visions Clinical Reserach

Boynton Beach, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Altus Research

Lake Worth, Florida, United States

Site Status

New Age Medical Reserach Group

Miami, Florida, United States

Site Status

Comprehensive Clinical Trials, LLC

West Palm Beach, Florida, United States

Site Status

Atlanta North Gynecology

Roswell, Georgia, United States

Site Status

Mount Vernon Clinical Research, LLC

Sandy Springs, Georgia, United States

Site Status

Cypress Medical Research Center. LLC

Wichita, Kansas, United States

Site Status

Meridian Health Care

Neptune City, New Jersey, United States

Site Status

Center for Women's Health and Wellness, LLC/ Women's Health Research Center

Plainsboro, New Jersey, United States

Site Status

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, United States

Site Status

Lyndhurst Clinical Research

Raleigh, North Carolina, United States

Site Status

Wake Research Associates

Raleigh, North Carolina, United States

Site Status

Hawthorne Medical Research, Inc.

Winstom-Salem, North Carolina, United States

Site Status

Lyndhurst Clinical Research

Winston-Salem, North Carolina, United States

Site Status

Columbus Center for Women;s Health Reserach

Columbus, Ohio, United States

Site Status

Clinical Research of Philadelphia, LLC

Philadelphia, Pennsylvania, United States

Site Status

Seatlle Womne's Health,Reserach, Gynecology

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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AM-ESD-001

Identifier Type: -

Identifier Source: org_study_id

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