Evaluate Long-Term Safety and Efficacy WC3011 (Estradiol Vaginal Cream)

A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in the Treatment of Symptoms of Vulvovaginal Atrophy in Postmenopausal Women

This is an open-label extension study evaluating the long-term safety and efficacy of WC3011 in non-hysterectomized, healthy, postmenopausal women with vulvovaginal atrophy.

Study Overview

• Status: Completed
• Conditions: Vulvovaginal Atrophy
• Intervention / Treatment: Drug: WC3011 Estradiol Vaginal Cream

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center, Inc.
    • Mobile, Alabama, United States, 36608
      • Warner Chilcott Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Women's Health Research
    • Phoenix, Arizona, United States, 85032
      • Precision Trials, LLC
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research-Scottsdale
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research-Tucson
    • Tucson, Arizona, United States, 85710
      • Radiant Research-Tucson
  • California
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • San Diego, California, United States, 92103
      • Genesis Center for Clinical Research
    • San Diego, California, United States, 92123
      • Women's Healthcare Inc.
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Visions Clinical Research
    • Clearwater, Florida, United States, 33759
      • Women's Medical Research Group, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Miami, Florida, United States, 33186
      • New Age Medical Research Corp
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Palm Beach Gardens, Florida, United States, 33410
      • OB-GYN Specialists of the Palm Beaches
    • Pinellas Park, Florida, United States, 33781
      • Radiant Research-St. Petersburg
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials, Llc
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Radiant Research-Atlanta
    • Savannah, Georgia, United States, 31406
      • Fellows Research Alliance, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60654
      • Radiant Research-Chicago
    • Springfield, Illinois, United States, 62703
      • Springfield Clinical, LLP
  • Indiana
    • Granger, Indiana, United States, 46530
      • The South Bend Clinic, LLP
  • Kansas
    • Overland Park, Kansas, United States, 66202
      • Radiant Research - Overland Park
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Bluegrass Clinical Research, Inc.
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • York Clinical Consulting
    • New Orleans, Louisiana, United States, 70115
      • Women Under Study
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Beyer Research
  • Minnesota
    • Chaska, Minnesota, United States, 55318
      • Ridgeview Research
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Affiliated Clinical Research
    • Las Vegas, Nevada, United States, 89128
      • Office of R. Garn Mabey, M.D.
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OB-GYN Associates, P.C.
    • Moorestown, New Jersey, United States, 08057
      • Phoenix OB-GYN Assoc., LLC
    • Plainsboro, New Jersey, United States, 08536
      • Women's Health Research Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Hawthorne Medical Research, Inc.
    • New Bern, North Carolina, United States, 28562
      • Eastern Carolina Women's Center
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Hawthorne Medical Research, Inc.
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
    • Columbus, Ohio, United States, 43213
      • The Columbus Center for Women's Health Research
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Clinical Trials of America, Inc.
    • Medford, Oregon, United States, 97504
      • Advanced Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Philadelphia Clinical Research, LLC
    • Pittsburgh, Pennsylvania, United States, 15206
      • Clinical Trials Research Services, LLC
    • Wexford, Pennsylvania, United States, 15090
      • Susan L. Floyd, MD, PC
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Fellows Research Alliance, Inc.
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
    • Dallas, Texas, United States, 75230
      • Practice Research Organization, Inc.
    • Dallas, Texas, United States, 75231
      • Radiant Research-Dallas
    • Houston, Texas, United States, 77030
      • Advances in Health, Inc
    • San Antonio, Texas, United States, 78229
      • Radiant Research-San Antonio
    • Webster, Texas, United States, 77598
      • Center for Reproductive Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research-Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research - Foothill Family Clinic South
    • Sandy, Utah, United States, 84070
      • Physicians' Research Options LLC
  • Virginia
    • Norfolk, Virginia, United States, 23507-1627
      • Eastern Virginia Medical School
    • Richmond, Virginia, United States, 23233
      • Virginia Women's Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology
    • Spokane, Washington, United States, 99207
      • North Spokane Women's Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Completed Study PR-04409.3 (NCT01400776)

Exclusion Criteria:

Developed any of the following during Study-PR04409.3 or has begun taking hormone therapy other than WC3011:

• Hypersensitivity to estrogen and/or progestin therapy
• Known or suspected premalignant or malignant disease (except successfully treated skin cancers)
• Manifestation of or treatment for significant cardiovascular disease, stroke or ischemic attack
• Insulin-dependent diabetes mellitus
• Smoking ≥ 15 cigarettes daily
• Uncontrolled hypertension - systolic blood pressure (BP) ≥ 160 mmHG or diastolic ≥ 95 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WC3011 Estradiol Vaginal Cream; WC3011 estradiol vaginal cream 3 times a week for up to 40 weeks.	Drug: WC3011 Estradiol Vaginal Cream; WC3011 estradiol vaginal cream, 3 times a week for 40 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Endometrial Biopsy Results at Final Visit	The endometrial biopsy results was categorized as: normal results categorized as atrophic/inactive or proliferative, unsatisfactory with endometrial thickness ≤4 mm and missing biopsy with endometrial thickness ≤4 mm; abnormal results categorized as polyp, hyperplasia, and carcinoma; unknown result categorized as unsatisfactory with endometrial thickness >4 mm, missing biopsy with endometrial thickness >4 mm, unsatisfactory without transvaginal ultrasonography (TVU) result and missing biopsy without TVU result. The duration of estradiol exposure was combination of studies PR-04409.3 and PR-04509.	Final Visit (Day closest to Day 281)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Participants Self-Assessment of the Symptoms of Vulvovaginal Atrophy (VVA) at Each Post-baseline Timepoints	Self-Assessment of the symptoms of VVA was evaluated for vaginal dryness, vaginal Itching, dysuria, and dyspareunia by a questionnaire. Questionnaire consisted of 5 questions scaled from 0 to 3 level of intensity, where 0-none indicated symptom not present; 1-mild indicated symptom is present but may be intermittent; does not interfere with your activities or lifestyle; 2-moderate indicated symptom is present, aware of the symptom but activities and lifestyle are only occasionally affected; 3-severe indicated usually aware and bothered by the symptom and have modified your activities and/or lifestyle due to the symptom. Higher score indicated most bothersome symptoms. A negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study.	Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Weeks 4, 8, 16, 24, 32, 40 and Final Visit (Day closest to Day 281)
Change From Baseline in Vaginal Cytology: Percentage of Superficial Vaginal Cells	Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of superficial cells. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study.	Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281)
Change From Baseline in Vaginal Cytology: Percentage of Parabasal Vaginal Cells	Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of parabasal cells. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study.	Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281)
Change From Baseline in Vaginal pH	Vaginal pH was obtained at final visit of the study. The pH was a numeric value from 0 to 14 expressing the acidity or alkalinity of the vaginal fluids where 7 was neutral, lower values were more acidic (values of 0-6) and higher values more alkaline (values of 8-14). A negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study.	Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281)
Change From Baseline as Per Investigator's Assessment of Each of the Signs of VVA	Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to the signs of VVA: atrophy, pallor, vaginal dryness, friability, and petechiae scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3= severe. The negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study.	Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281)
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)	An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. TEAE are defined as those AEs with onset date on or after the first dose date of study drug in Study PR-04509, or adverse events that worsen after the first dose date of study drug in Study PR-04509.	Up to Week 40

Collaborators and Investigators

• Sponsor: Warner Chilcott

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2011
• Primary Completion (Actual): December 3, 2012
• Study Completion (Actual): December 3, 2012

Study Registration Dates

• First Submitted: October 17, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Postmenopausal Women; Vaginal Dryness; Postmenopausal Vulvovaginal Atrophy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: PR-04509

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No