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

NCT01779947 | Completed Phase 3

• 1 other identifier: AM-ESD-001
• Study Type: interventional
• Target: 519
• Locations: 1 country
• Sites: 25

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.

Conditions

Atrophic Vaginitis Due to Menopause

Outcome Measures

Primary Outcomes (1)

• Responders

  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

  Day 15 (1 day after the administration of the 14th dose of study treatment)

Secondary Outcomes (1)

• Treatment Success

  Day 15

Study Arms (3)

Estradiol Vaginal Insert 10 mcg

EXPERIMENTAL

Estradiol Vaginal Insert 10 mcg - Test Product

Drug: Estradiol Vaginal Tablets 10 mcg

Vagifem Tablets 10 mcg

ACTIVE COMPARATOR

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

Drug: Estradiol Vaginal Tablets 10 mcg

Placebo

PLACEBO COMPARATOR

Placebo for the test product Estradiol Vaginal Tablets 10 mcg

Drug: placebo

Interventions

Estradiol Vaginal Tablets 10 mcg DRUG

Also known as: Vagifem®

Estradiol Vaginal Insert 10 mcg; Vagifem Tablets 10 mcg

placebo DRUG

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Amneal Pharmaceuticals, LLC: lead

Study Sites (25)

Medical Affiliated Research center, Inc.

Huntsville, Alabama, 35801, United States

Location

Montogmery Women's Health Associates

Montgomery, Alabama, 36117, United States

Location

Medical Center for Clinical Research

San Diego, California, 92108, United States

Location

Women's Health Care Research Corp.

San Diego, California, 92123, United States

Location

Downtown Women's Health care

Denver, Colorado, 80218, United States

Location

Horizons Clinical Research Center

Denver, Colorado, 80220, United States

Location

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

Washington D.C., District of Columbia, 20036, United States

Location

Visions Clinical Reserach

Boynton Beach, Florida, 33472, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Altus Research

Lake Worth, Florida, 33461, United States

Location

New Age Medical Reserach Group

Miami, Florida, 33186, United States

Location

Comprehensive Clinical Trials, LLC

West Palm Beach, Florida, 33409, United States

Location

Atlanta North Gynecology

Roswell, Georgia, 30075, United States

Location

Mount Vernon Clinical Research, LLC

Sandy Springs, Georgia, 30328, United States

Location

Cypress Medical Research Center. LLC

Wichita, Kansas, 67226, United States

Location

Meridian Health Care

Neptune City, New Jersey, 07753, United States

Location

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

Plainsboro, New Jersey, 08536, United States

Location

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, 12601, United States

Location

Lyndhurst Clinical Research

Raleigh, North Carolina, 27607, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Hawthorne Medical Research, Inc.

Winstom-Salem, North Carolina, 27103, United States

Location

Lyndhurst Clinical Research

Winston-Salem, North Carolina, 27103, United States

Location

Columbus Center for Women;s Health Reserach

Columbus, Ohio, 43213, United States

Location

Clinical Research of Philadelphia, LLC

Philadelphia, Pennsylvania, 19114, United States

Location

Seatlle Womne's Health,Reserach, Gynecology

Seattle, Washington, 98105, United States

Location

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• W. Todd Kays, PhD

  Amneal Pharmaceuticals, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2013
• First Posted: January 30, 2013
• Study Start: March 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 26, 2014

Record last verified: 2014-06

Locations

US (25)