Multicenter Study to Evaluate Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in Postmenopausal Women

A Randomized, Multicenter, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of WC3011 in Postmenopausal Women

The primary objective of this study is to compare the efficacy of WC3011 with placebo vaginal gel in postmenopausal women for the relief of vaginal dryness caused by vaginal atrophy as measured by self-assessment, vaginal pH and vaginal smear.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 576
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Warner Chilcott Investigational Study Site
    • Mobile, Alabama, United States, 36608
      • Warner Chilcott Investigational Study Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Warner Chilcott Investigational Study Site
    • Scottsdale, Arizona, United States, 85251
      • Warner Chilcott Investigational Study Site
    • Tucson, Arizona, United States, 85712
      • Warner Chilcott Investigational Study Site
  • California
    • San Diego, California, United States, 92103
      • Warner Chilcott Investigational Study Site
    • San Diego, California, United States, 92108
      • Warner Chilcott Investigational Study Site
    • San Diego, California, United States, 92123
      • Warner Chilcott Investigational Study Site
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Warner Chilcott Investigational Study Site
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Warner Chilcott Investigational Study Site
    • Clearwater, Florida, United States, 33759
      • Warner Chilcott Investigational Study Site
    • Jacksonville, Florida, United States, 32216
      • Warner Chilcott Investigational Study Site
    • Miami, Florida, United States, 33143
      • Warner Chilcott Investigational Study Site
    • Miami, Florida, United States, 33186
      • Warner Chilcott Investigational Study Site
    • Ormond Beach, Florida, United States, 32174
      • Warner Chilcott Investigational Study Site
    • Palm Beach Gardens, Florida, United States, 33410
      • Warner Chilcott Investigational Study Site
    • Pinellas Park, Florida, United States, 33781
      • Warner Chilcott Investigational Study Site
    • West Palm Beach, Florida, United States, 33409
      • Warner Chilcott Investigational Study Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Warner Chilcott Investigational Study Site
    • Roswell, Georgia, United States, 30075
      • Warner Chilcott Investigational Study Site
    • Savannah, Georgia, United States, 31406
      • Warner Chilcott Investigational Study Site
  • Indiana
    • Granger, Indiana, United States, 46530
      • Warner Chilcott Investigational Study Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Warner Chilcott Investigational Study Site
    • New Orleans, Louisiana, United States, 70115
      • Warner Chilcott Investigational Study Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Warner Chilcott Investigational Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Warner Chilcott Investigational Study Site
    • Las Vegas, Nevada, United States, 89113
      • Warner Chilcott Investigational Study Site
  • New Jersey
    • Moorestown, New Jersey, United States, 08057
      • Warner Chilcott Investigational Study Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Warner Chilcott Investigational Study Site
    • New Bern, North Carolina, United States, 28562
      • Warner Chilcott Investigational Study Site
    • Winston-Salem, North Carolina, United States, 27103
      • Warner Chilcott Investigational Study Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Warner Chilcott Investigational Study Site
    • Columbus, Ohio, United States, 43213
      • Warner Chilcott Investigational Study Site
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Warner Chilcott Investigational Study Site
    • Philadelphia, Pennsylvania, United States, 19114
      • Warner Chilcott Investigational Study Site
    • Pittsburgh, Pennsylvania, United States, 15206
      • Warner Chilcott Investigational Study Site
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Warner Chilcott Investigational Study Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Warner Chilcott Investigational Study Site
    • Dallas, Texas, United States, 75231
      • Warner Chilcott Investigational Study Site
    • Dallas, Texas, United States, 75234
      • Warner Chilcott Investigational Study Site
    • Houston, Texas, United States, 77030
      • Warner Chilcott Investigational Study Site
    • San Antonio, Texas, United States, 78229
      • Warner Chilcott Investigational Study Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Warner Chilcott Investigational Study Site
    • Salt Lake City, Utah, United States, 84121
      • Warner Chilcott Investigational Study Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Warner Chilcott Investigational Study Site
    • Richmond, Virginia, United States, 23233
      • Warner Chilcott Investigational Study Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Warner Chilcott Investigational Study Site
    • Spokane, Washington, United States, 99207
      • Warner Chilcott Investigational Study Site

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:

• Signed informed consent
• Moderate to severe vaginal dryness
• Postmenopausal meeting one of the following: 12 months spontaneous amenorrhea, 6 months spontaneous amenorrhea with serum Follicle-stimulating hormone (FSH) > 40 milli-International Unit (mIU)/mL, 6 weeks postsurgical bilateral oophorectomy confirmed by surgical report, ultrasound or serum FSH > 40 mIU/mL, 6 weeks postsurgical hysterectomy with ovary failure confirmed by serum FSH > 40 mIU/mL
• Age ≥ 40 years or if bilateral oophorectomy ≥ 35 years
• Vaginal pH >5.0
• Less than or equal 5% superficial cells on vaginal wall cytologic smear
• Normal breast exam; if > 40 years, documentation of negative mammogram

Exclusion Criteria:

• Randomization in PR-04409, participation in clinical trial or use of investigational drug within 30 days prior to screening
• Smokes ≥ 15 cigarettes/day
• Known or suspected premalignant or malignant disease
• Cardiovascular disease, insulin-dependent diabetes mellitus, congestive heart failure, stroke or ischemic attack, thrombophlebitis or thromboembolic disorder
• Increased frequency/severity headaches with estrogen therapy
• Drug addiction/alcohol abuse within last 2 years
• Currently taking St. John's Wort or anticoagulant
• Uncontrolled hypertension or thyroid disorder, clinically significant depression or untreated urinary tract infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vehicle (2 Times/Week); Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	Drug: Vehicle; Vehicle Cream applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks
Placebo Comparator: WC3011 Estradiol Vaginal Cream (2 Times/Week); WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	Drug: WC3011 Estradiol Vaginal Cream; WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment	Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) to final assessment (Up to Week 12)
Change From Baseline in Vaginal pH to Final Assessment	Vaginal pH was obtained at baseline and 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. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) to final assessment (Up to Week 12)
Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment	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. A positive change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) to final assessment (Up to Week 12)
Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment	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. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) to final assessment (Up to Week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12	Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement.	Baseline (Day 0) to Weeks 2, 4, 8, and 12
Change From Baseline in Participants Self-Assessment of the Symptoms of VVA	Self-Assessment of the symptoms of VVA (vaginal and/or vulvar irritation/ Itching, dysuria, and dyspareunia) were evaluated by a questionnaire. Each symptom was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final Assessment is defined as the last available post-baseline assessment for the given efficacy endpoint.	Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity	Vaginal bleeding associated with sexual activity was assessed by participants as either "present" or "absent". Number of participants with assessment "present" are reported. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment
Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment	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 each graded on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores are worse. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.	Baseline (Day 0) to Week 12 and Final Assessment
Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12	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. A positive change from Baseline indicates improvement.	Baseline (Day 0) to Week 12
Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12	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. A negative change from Baseline indicates improvement.	Baseline (Day 0) to Week 12

Collaborators and Investigators

• Sponsor: Warner Chilcott
• Investigators: Study Director: Anna Chan, PharmD, Warner Chilcott

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2013
• Primary Completion (Actual): November 19, 2013
• Study Completion (Actual): November 19, 2013

Study Registration Dates

• First Submitted: March 13, 2013
• First Submitted That Met QC Criteria: March 18, 2013
• First Posted (Estimate): March 21, 2013

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: estrogen; vaginal dryness; vaginal 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-05812

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No