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

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

The purpose of the study is to determine if WC3011 is safe and effective in treating the symptom of painful intercourse secondary to vulvovaginal atrophy as measured by participant self-assessment when compared to vehicle.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Warner Chilcott Investigational Study Site
    • Mobile, Alabama, United States, 36608
      • Warner Chilcott Investigational Study Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Warner Chilcott Investigational Study Site
    • 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
    • Tucson, Arizona, United States, 85710
      • Warner Chilcott Investigational Study Site
  • California
    • Sacramento, California, United States, 95821
      • Warner Chilcott Investigational Study Site
    • 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
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • 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, 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, 30342
      • 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
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • 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
  • Minnesota
    • Chaska, Minnesota, United States, 55318
      • Warner Chilcott Investigational Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Warner Chilcott Investigational Study Site
    • Las Vegas, Nevada, United States, 89128
      • 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
    • Raleigh, North Carolina, United States, 27607
      • Warner Chilcott Investigational Study Site
    • Winston-Salem, North Carolina, United States, 27103
      • Warner Chilcott Investigational Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Warner Chilcott Investigational Study Site
    • 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
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Warner Chilcott Investigational Study Site
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Warner Chilcott Investigational Study Site
    • Greer, South Carolina, United States, 29650
      • Warner Chilcott Investigational Study Site
  • Texas
    • Austin, Texas, United States, 78759
      • Warner Chilcott Investigational Study Site
    • 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
    • South Jordan, Utah, United States, 84095
      • Warner Chilcott Investigational Study Site
  • Virginia
    • Norfolk, Virginia, United States, 23507-1627
      • 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:

• Sexually active with self-identified dyspareunia (pain with sexual activity), at least moderate to severe and most bothersome symptom of vulvovaginal atrophy (VVA)
• Postmenopausal and meets 1 of the following: 12 months spontaneous amenorrhea, 6 months spontaneous amenorrhea with FSH (follicle stimulating hormone) >40 mIU/mL,6 weeks postsurgical bilateral oophorectomy with confirmation by FSH >40 mIU/mL, surgical report or ultrasound, 6 weeks postsurgical hysterectomy with ovary failure confirmed by FSH >40 mIU/mL
• Age ≥40 years; ≥35 with bilateral oophorectomy
• Vaginal pH >5.0
• Less than or equal to 5% superficial cells on vaginal wall cytologic smear
• Normal clinical breast exam or negative mammogram if ≥ 40 years of age
• Negative urine pregnancy test (non-hysterectomized and <12 months amenorrhea)

Exclusion Criteria:

• Enrollment in Sponsor's Study PR-04409 or PR-05812
• Participation in clinical trial or use of investigational drug within 30 days prior to screening
• Known hypersensitivity to estrogen and/or progestin therapy
• Known or suspected premalignant or malignant disease or history steroid-dependent malignancy
• Manifestation or treatment for significant cardiovascular disease (congestive heart failure, stroke or ischemic attack, myocardial infarction, coronary artery bypass, percutaneous angioplasty or >50% angiographic narrowing of coronary artery
• Thrombophlebitis or thromboembolic disorder or history of
• Insulin-dependent diabetes mellitus
• Increased frequency or severity of headaches while on hormone or estrogen therapy
• Currently taking St. John's Wort
• Drug/alcohol addiction within past 2 years
• Treatment with anticoagulants (heparin or warfarin)
• Smoking ≥15 cigarettes/day

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
Active Comparator: Vehicle (3 Times/Week); Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	Drug: Vehicle; Daily for 14 days followed by 3 times per week for 10 weeks
Experimental: WC3011 Estradiol Vaginal Cream (3 Times/Week); WC3011 Estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.	Drug: WC3011 Estradiol Vaginal Cream; Daily for 14 days followed by 3 times per week for 10 weeks; Other Names: WC3011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment	Participant's self-assessment of the symptom of VVA (dyspareunia) was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher score indicates 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 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 post-baseline assessment for the given efficacy endpoint.	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 the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12	Participant's self-assessment of the symptom of VVA (dyspareunia) was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher score indicates the most bothersome symptoms. A negative change from Baseline indicates improvement.	Baseline to Weeks 2, 4, 8 and 12
Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment	Self-Assessment of the symptoms of VVA, other than dyspareunia and vaginal bleeding associated with sexual activity, (vaginal and/or vulvar irritation/itching, dysuria and vaginal dryness) 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 (Up to Week 12)
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit	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 post-baseline assessment for the given efficacy endpoint.	Baseline (Day 0), Weeks 2, 4, 8, 12 and final assessment (Up to Week 12)
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 (Up to Week 12)
Change From Baseline in Vaginal pH to Week 12	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.	Baseline to Week 12
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 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 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): April 12, 2013
• Primary Completion (Actual): November 20, 2013
• Study Completion (Actual): November 20, 2013

Study Registration Dates

• First Submitted: April 25, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimate): May 3, 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: Postmenopausal; Dyspareunia; Vulvovaginal Atrophy
• Additional Relevant MeSH Terms: Mental Disorders; Pathological Conditions, Anatomical; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Atrophy; Dyspareunia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: PR-08112