A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis

NCT02195986 | Completed Phase 3 Results

• 1 other identifier: EVCR-11196
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this study is to determine the therapeutic equivalence of Mylan's estradiol vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7 day treatment.

Conditions

Atrophic Vaginitis

Keywords

vaginal dryness; vaginal and/or vulvar irritation/itching; dysuria; vaginal pain and bleeding associated with sexual activity; vaginal atrophy

Outcome Measures

Primary Outcomes (2)

• Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence

  Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream or Estrace® that were identified as responders at the end of the treatment period on Study Day 8. A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.

  Study Day 8

• Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo

  Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream, Estrace®, or Placebo that were identified as responders at the end of the treatment period on Study Day 8. A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.

  Study Day 8

Secondary Outcomes (2)

• Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence

  Day 8

• Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Comparison to Placebo

  Day 8

Study Arms (3)

Estradiol Vaginal Cream

EXPERIMENTAL

Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.

Drug: Estradiol Vaginal Cream, 0.01%

Estrace® 0.01% cream

ACTIVE COMPARATOR

Estrace® 0.01% vaginal cream, administered once daily for 7 days.

Drug: Estrace® 0.01% cream

Placebo Vaginal Cream

PLACEBO COMPARATOR

Placebo Vaginal Cream, administered once daily for 7 days.

Drug: Placebo Vaginal Cream

Interventions

Estradiol Vaginal Cream, 0.01% DRUG

Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)

Estradiol Vaginal Cream

Estrace® 0.01% cream DRUG

Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)

Estrace® 0.01% cream

Placebo Vaginal Cream DRUG

Placebo Vaginal Cream ( 1 x 2 g for 7 days)

Placebo Vaginal Cream

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of providing informed consent.
• Age: 40-70 years old.
• Sex: Female
• Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/ml or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Weight: At least 48 kg with all subjects having a Body Mass Index less than or equal to 38 kg/m2 but greater than or equal to 19 kg/m2.
• Baseline evaluation requirements:
• ≤5% superficial cells on vaginal smear cytology
• Vaginal pH \> 5.0
• At least one patient self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy (VVA) from the following list that is identified by the subject:
• Vaginal dryness
• Vaginal and/or vulvar irritation/itching
• Dysuria
• Vaginal pain associated with sexual activity
• Vaginal bleeding associated with sexual activity (absence vs. presence)
• All subjects should be judged to be eligible for participation in this study by the principal or sub-investigator physician during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:

You may not qualify if:

• Serum Chemistry
• Hematology
• Coagulogram
• Urinalysis
• normal or non-clinically significant 12- Lead ECG.
• negative urine cotinine test.
• For women with an intact uterus, an endometrial thickness \< 5 mm as determined by vaginal ultrasonography.
• If warranted, other tests or examinations may be performed at the discretion of the Principal Investigator or responsible physician.
• Ability to use applicator properly.
• Institutionalized subjects will not be used.
• Any contraindication to estrogen therapy.
• Social Habits:
• Use of any tobacco-containing products within 1 year of the start of the study.
• Regular intake of more than 7 units of alcohol per week.
• Beginning any new regimens of vitamins or herbal products within 7 days prior to the initial dose of the study medication.

Sponsors & Collaborators

• Mylan Pharmaceuticals Inc: lead

Study Sites (21)

ARA-Arizona Research Associates

Tucson, Arizona, 85712, United States

Location

Axis Clinical Trials

Los Angeles, California, 90036, United States

Location

Northern CA Research

Sacramento, California, 95821, United States

Location

MCCR

San Diego, California, 92108, United States

Location

Women's Health Care Research Corp.

San Diego, California, 92123, United States

Location

MCB Clinical Research Centers

Colorado Springs, Colorado, 80910, United States

Location

Downtown Women's Health Care

Denver, Colorado, 80209, United States

Location

Horizons Clinical Research Center, LLC

Denver, Colorado, 80220, United States

Location

Sunrise Medical Research

Coral Springs, Florida, 33065, United States

Location

Health Awareness, Inc.

Jupiter, Florida, 33458, United States

Location

Meridien Research

Lakeland, Florida, 33805, United States

Location

OB-GYN Associates of Mid Florida

Leesburg, Florida, 34748, United States

Location

SouthCoast Research Center

Miami, Florida, 33136, United States

Location

Veritas Research, Corp.

Miami Lakes, Florida, 33014, United States

Location

Physician Care Clinical Research LLC

Sarasota, Florida, 34239, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

Sunrise Medical Research

Tamarac, Florida, 33351, United States

Location

Comprehensive Clinical Trials, LLC

West Palm Beach, Florida, 33409, United States

Location

Georgia Center for Women

Atlanta, Georgia, 30312, United States

Location

Lawrence OB/GYN Clinical Research, LLC

Lawrenceville, New Jersey, 08690, United States

Location

Women's Health Research Center/The Center for Women's Health & Wellness, LLC

Plainsboro, New Jersey, 08536, United States

Location

MeSH Terms

Conditions

Atrophic Vaginitis; Pruritus; Dysuria

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lower Urinary Tract Symptoms; Urological Manifestations

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

Results Point of Contact

• Title: Abhijit Barve, Head of Global Clinical Research
• Organization: Mylan Inc.

abhijit.barve@mylan.com

Study Officials

• Matt Hummel, Ph.D.

  Mylan Pharmaceuticals Inc

  STUDY CHAIR

• Ronald Ackerman, M.D.

  Comprehensive Clinical Trials, LLC

  PRINCIPAL INVESTIGATOR

• James Andersen, M.D.

  Meridien Research

  PRINCIPAL INVESTIGATOR

• Keith Aqua, M.D.

  Visions Clinical Research

  PRINCIPAL INVESTIGATOR

• Theodore Cooper, M.D.

  Horizons Clinical Research Center, LLC

  PRINCIPAL INVESTIGATOR

• Scott Eder, M.D.

  Women's Health Research Center/The Center for Women's Health & Wellness, LLC

  PRINCIPAL INVESTIGATOR

• William Koltun, M.D.

  Medical Center for Clinical Research

  PRINCIPAL INVESTIGATOR

• Gigi Lefebvre, M.D.

  Meridien Research

  PRINCIPAL INVESTIGATOR

• Leonard Ranasinghe, M.D.

  Northern CA Research

  PRINCIPAL INVESTIGATOR

• Rovena Reagan, M.D.

  Women's Health Care Research Corp.

  PRINCIPAL INVESTIGATOR

• Ronald Surowitz, D.O.

  Health Awareness, Inc.

  PRINCIPAL INVESTIGATOR

• Steven Sussman, M.D.

  Lawrence OB/GYN Clinical Research, LLC

  PRINCIPAL INVESTIGATOR

• G. Michael Swor, M.D.

  Physician Care Clinical Research LLC

  PRINCIPAL INVESTIGATOR

• Olga Tudela, M.D.

  Veritas Research., Corp.

  PRINCIPAL INVESTIGATOR

• Arthur Waldbaum, M.D.

  Downtown Women's Health Care

  PRINCIPAL INVESTIGATOR

• Maria C Fernandez, M.D.

  South Coast Research Center, Inc.

  PRINCIPAL INVESTIGATOR

• Gary Carson, M.D

  Northern CA Research

  PRINCIPAL INVESTIGATOR

• Lydie Hazan, M.D.

  Axis Clinical Trials

  PRINCIPAL INVESTIGATOR

• Alfred Moffett, M.D.

  OB-GYN Associates of Mid Florida

  PRINCIPAL INVESTIGATOR

• Tracey Lemon, M.D.

  Georgia Center for Women

  PRINCIPAL INVESTIGATOR

• Steven Foley, M.D.

  MCB Clinical Research Centers, LLC

  PRINCIPAL INVESTIGATOR

• Jason Haffizulla, M.D.

  Sunrise Medical Research, Inc.

  PRINCIPAL INVESTIGATOR

• Robert Hunter, M.D.

  ARA-Arizona Research Associates

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 21, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 9, 2022
• Results First Posted: September 6, 2017

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)