A Safety and Efficacy Study of Estradiol Vaginal Capsule in Postmenopausal Women With Vulvovaginal Atrophy

A Phase 2, Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate Safety and Efficacy of Three Doses of Estradiol Vaginal Capsule in Postmenopausal Women With Vulvovaginal Atrophy

This study will access the safety and efficacy of three doses of estradiol vaginal capsules in postmenopausal women with vulvovaginal atrophy.

Study Overview

• Status: Completed
• Conditions: Menopause; Vulvovaginal Atrophy; Dyspareunia
• Intervention / Treatment: Drug: Estradiol Vaginal Capsule (EVC); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research-Tucson
  • California
    • San Diego, California, United States, 92103
      • Genesis Center for Clinical Research
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
  • Florida
    • Clearwater, Florida, United States, 33759
      • Women's Medical Research Group, LLC
    • Pinellas Park, Florida, United States, 33781
      • Radiant Research, Inc.
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials, Llc
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Fellows Research Alliance, Inc
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Beyer Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Office of R. Garn Mabey, M.D.
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Carolina Women's Research and Wellness Center
    • 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
      • Women's Health Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Of Philadelphia, Llc
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Fellows Research Alliance, Inc
  • Texas
    • Dallas, Texas, United States, 75231
      • Radiant Research, Inc.
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
  • Virginia
    • 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:

• Clinical diagnosis of vulvovaginal atrophy due to post menopause
• Age ≥ 40 years or if bilateral oophorectomy ≥ 35 years
• Moderate to severe vaginal dryness
• Normal breast exam; if > 40 years
• Vaginal pH > 5.0
• < 5% superficial cells on vaginal wall cytology smear

Exclusion Criteria:

• Known hypersensitivity to estrogen and/or progestin therapy
• Known or suspected premalignant or malignant disease
• Undiagnosed abnormal genital bleeding
• A history of or treatment for significant cardiovascular disease, congestive heart failure, or stroke
• Active or known protein C, protein S, or antithrombin deficient, or other known thrombophilic disorders or thromboembolic events
• Increased frequency/severity headaches with estrogen therapy
• Smokes ≥ 15 cigarettes/day

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estradiol Vaginal Capsule 0.003 mg; Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks	Drug: Estradiol Vaginal Capsule (EVC); Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks
Experimental: Estradiol Vaginal Capsule 0.01 mg; Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks	Drug: Estradiol Vaginal Capsule (EVC); Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks
Experimental: Estradiol Vaginal Capsule 0.02 mg; Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks	Drug: Estradiol Vaginal Capsule (EVC); Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks
Placebo Comparator: Placebo; Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks	Drug: Placebo; Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the percentage of vaginal superficial cells	Baseline (Week 0) to Final Visit (Week 6)
Change in the percentage of vaginal parabasal cells	Baseline (Week 0) to Final Visit (Week 6)
Change in vaginal pH	Baseline (Week 0) to Final Visit (Week 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the investigator assessment of VVA measured by scoring the vaginal health in 5 categories using a 4-point scale	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of vaginal dryness reported as the most bothersome symptom	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of dyspareunia reported as the most bothersome symptom	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of dysuria	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of vaginal and/or vulvar irritation/itching	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of vaginal dryness in patients where vaginal dryness was not reported as the most bothersome symptom	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Change in subject's self-assessment of dyspareunia in patients where dyspareunia was not reported as the most bothersome symptom	Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3.	Baseline (Week 0) to Final Visit (Week 6)
Self-assessment by sexually active participants as to the presence or absence of vaginal bleeding	Total number of participants who were sexually active assessed if vaginal bleeding was present or absent.	Baseline (Week 0) to Final Visit (Week 6)

Collaborators and Investigators

• Sponsor: Warner Chilcott
• Investigators: Study Director: Vilma Sniukiene, MD, Allergan

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2016
• Primary Completion (Actual): November 14, 2016
• Study Completion (Actual): November 14, 2016

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 28, 2016
• First Posted (Estimate): February 2, 2016

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 21, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• 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: EVC-MD-01

Drug and device information, study documents

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