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Trial record 31 of 2094 for:    ESTRADIOL

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01779947
Recruitment Status : Completed
First Posted : January 30, 2013
Last Update Posted : June 26, 2014
Information provided by (Responsible Party):
Amneal Pharmaceuticals, LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Atrophic Vaginitis Due to Menopause Drug: Estradiol Vaginal Tablets 10 mcg Drug: placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 519 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : March 2012
Actual Primary Completion Date : September 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Arm Intervention/treatment
Experimental: Estradiol Vaginal Insert 10 mcg
Estradiol Vaginal Insert 10 mcg - Test Product
Drug: Estradiol Vaginal Tablets 10 mcg
Other Name: Vagifem®

Active Comparator: Vagifem Tablets 10 mcg
Vagifem® (Estradiol Vaginal Tablets) 10 mcg - Reference Listed Drug
Drug: Estradiol Vaginal Tablets 10 mcg
Other Name: Vagifem®

Placebo Comparator: Placebo
Placebo for the test product Estradiol Vaginal Tablets 10 mcg
Drug: placebo

Primary Outcome Measures :
  1. Responders [ Time Frame: Day 15 (1 day after the administration of the 14th dose of study treatment) ]
    A responder was defined as a subject with at least a 25% reduction from baseline in the sum of % basal/parabasal and % intermediate cells on vaginal cytology AND vaginal pH < 5.0 with a change from baseline vaginal pH of at least 0.5, where baseline values were collected at Visit 1

Secondary Outcome Measures :
  1. Treatment Success [ Time Frame: Day 15 ]
    Treatment success was defined as a subject who achieved a score of 0 (none) or 1 (mild) at Visit 3 for the Most Bothersome Symptom (MBS) if her MBS was vaginal dryness, vaginal or vulvar irritation or itching, dysuria or vaginal pain associated with sexual activity, or a result of absence (0) at Visit 3 if her MBS was vaginal bleeding with sexual activity.

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01779947

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Sponsors and Collaborators
Amneal Pharmaceuticals, LLC
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Study Chair: W. Todd Kays, PhD Amneal Pharmaceuticals, LLC

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Responsible Party: Amneal Pharmaceuticals, LLC Identifier: NCT01779947     History of Changes
Other Study ID Numbers: AM-ESD-001
First Posted: January 30, 2013    Key Record Dates
Last Update Posted: June 26, 2014
Last Verified: June 2014
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Polyestradiol phosphate
Atrophic Vaginitis
Vaginal Diseases
Genital Diseases, Female
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female