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