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

Information source: Amneal Pharmaceuticals, LLC
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Atrophic Vaginitis Due to Menopause

Intervention: Estradiol Vaginal Tablets 10 mcg (Drug); placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Amneal Pharmaceuticals, LLC

Official(s) and/or principal investigator(s):
W. Todd Kays, PhD, Study Chair, Affiliation: Amneal Pharmaceuticals, LLC


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.

Clinical Details

Official title: An Investigator-Blind, Randomized, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, USP 10 mcg and Vagifem (Estradiol Vaginal Tablets) 10 mcg and Compare Both Active Treatments to a Placebo Control in Female Subjects With Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy Associated With Menopause

Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Responders

Secondary outcome: Treatment Success


Minimum age: 30 Years. Maximum age: 75 Years. Gender(s): Female.


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


- 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


- 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


- 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


- 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.

Locations and Contacts

Medical Affiliated Research center, Inc., Huntsville, Alabama 35801, United States

Montogmery Women's Health Associates, Montgomery, Alabama 36117, United States

Medical Center for Clinical Research, San Diego, California 92108, United States

Women's Health Care Research Corp., San Diego, California 92123, United States

Downtown Women's Health care, Denver, Colorado 80218, United States

Horizons Clinical Research Center, Denver, Colorado 80220, United States

James A. Simon, MD PC/ Women's Health and Research Consultants, Washington, District of Columbia 20036, United States

Visions Clinical Reserach, Boynton Beach, Florida 33472, United States

Jacksonville Center for Clinical Research, Jacksonville, Florida 32216, United States

Altus Research, Lake Worth, Florida 33461, United States

New Age Medical Reserach Group, Miami, Florida 33186, United States

Comprehensive Clinical Trials, LLC, West Palm Beach, Florida 33409, United States

Atlanta North Gynecology, Roswell, Georgia 30075, United States

Mount Vernon Clinical Research, LLC, Sandy Springs, Georgia 30328, United States

Cypress Medical Research Center. LLC, Wichita, Kansas 67226, United States

Meridian Health Care, Neptune, New Jersey 07753, United States

Center for Women's Health and Wellness, LLC/ Women's Health Research Center, Plainsboro, New Jersey 08536, United States

Premier Medical Group of the Hudson Valley, Poughkeepsie, New York 12601, United States

Lyndhurst Clinical Research, Raleigh, North Carolina 27607, United States

Wake Research Associates, Raleigh, North Carolina 27612, United States

Hawthorne Medical Research, Inc., Winstom-Salem, North Carolina 27103, United States

Lyndhurst Clinical Research, Winston-Salem, North Carolina 27103, United States

Columbus Center for Women;s Health Reserach, Columbus, Ohio 43213, United States

Clinical Research of Philadelphia, LLC, Philadelphia, Pennsylvania 19114, United States

Seatlle Womne's Health,Reserach, Gynecology, Seattle, Washington 98105, United States

Additional Information

Starting date: March 2012
Last updated: June 25, 2014

Page last updated: August 23, 2015

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