A Clinical Study to Evaluate Ospemifene in the Treatment of Vulvar and Vaginal Atrophy in Postmenopausal Women

Efficacy and Safety of Ospemifene in the Treatment of Vulvar and Vaginal Atrophy (VVA) in Postmenopausal Women: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing Oral Ospemifene 30 and 60 Mg Daily Doses With Placebo

The purpose of this study is to determine whether ospemifene is more effective than placebo in the treatment of vulvar and vaginal atrophy (VVA) in postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Atrophy; Vaginal Diseases
• Intervention / Treatment: Drug: Ospemifene 30 mg; Drug: Nonhormonal vaginal lubricant; Drug: Ospemifene 60 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 826
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Naturally or surgically postmenopausal
• Moderate or severe symptoms of vaginal atrophy (ie, vaginal dryness, irritation or itching, difficult or painful urination, pain or bleeding with intercourse)
• Vaginal pH greater than 5.0
• 5% or fewer superficial cells in maturation index of vaginal smear

Exclusion Criteria:

• Evidence of endometrial hyperplasia, endometrial cancer, or other abnormal endometrial pathology
• Abnormal Pap smear
• Uterine bleeding of unknown origin or uterine polyps
• Current vaginal infection requiring medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ospemifene 30 mg/day and nonhormonal vaginal lubricant; Subjects will receive a single dose (1 tablet) of ospemifene 30 mg each morning with food for 12 weeks. The vaginal lubricant (K-Y® Brand Jelly) should be applied as needed and its use should be recorded in the medication diary. The first dose of the study drug will be administered at the clinic at Visit 2.	Drug: Ospemifene 30 mg; 1 tablet (dose 30 mg/day) taken each morning with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (Week 12).; Drug: Nonhormonal vaginal lubricant; Subjects should apply the vaginal lubricant as needed and record the usage in the medication diary.; Other Names: K-Y® Brand Jelly
Experimental: Ospemifene 60 mg/day and nonhormonal vaginal lubricant; Subjects will receive a single dose (1 tablet) of ospemifene 60 mg each morning with food for 12 weeks. The vaginal lubricant (K-Y® Brand Jelly) should be applied as needed and its use should be recorded in the medication diary. The first dose of the study drug will be administered at the clinic at Visit 2.	Drug: Nonhormonal vaginal lubricant; Subjects should apply the vaginal lubricant as needed and record the usage in the medication diary.; Other Names: K-Y® Brand Jelly; Drug: Ospemifene 60 mg; 1 tablet (dose 60 mg/day) taken each morning with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (Week 12).
Placebo Comparator: Placebo tablets and nonhormonal vaginal lubricant; Subjects will receive a single dose (1 tablet) of placebo each morning with food for 12 weeks. The vaginal lubricant (K-Y® Brand Jelly) should be applied as needed and its use should be recorded in the medication diary. The first dose of the study drug will be administered at the clinic at Visit 2.	Drug: Nonhormonal vaginal lubricant; Subjects should apply the vaginal lubricant as needed and record the usage in the medication diary.; Other Names: K-Y® Brand Jelly; Drug: Placebo; 1 tablet taken each morning with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (Week 12).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Most Bothersome Vulvar and Vaginal Atrophy (VVA) Symptom (MBS) of Vaginal Dryness	This outcome measure was analyzed using Cochran-Mantel-Haenszel (CMH) row mean scores test controlling for study center and uterine status. VVA Symptom Score: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe	Baseline (Randomization) to Week 12
Mean Change From Baseline in the MBS of Vaginal Pain Associated With Sexual Activity	This outcome measure was analyzed using CMH row mean scores test controlling for study center and uterine status. VVA Symptom Score: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe	Baseline (Randomization) to Week 12
Mean Change From Baseline in Vaginal pH		Baseline (Screening) to Week 12
Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear		Baseline (Screening) to Week 12
Mean Change From Baseline in the Percentage of Superficial Cells in Maturation Index of Vaginal Smear		Baseline (Screening) to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Visual Evaluation of the Vagina	Exam Rating Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe	Baseline (Screening) to Week 12
Change From Baseline in Severity of VVA Symptoms	This outcome measure was analyzed using CMH row mean scores test controlling for study center and uterine status. VVA Symptom Score: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe	Baseline (Randomization) to Week 12
Change From Baseline in Estradiol Levels		Baseline (Screening) to Week 12
Change From Baseline in Follicle Stimulating Hormone Levels		Baseline (Screening) to Week 12
Change From Baseline in Luteinizing Hormone Levels		Baseline (Screening) to Week 12
Change From Baseline in Sex Hormone Binding Globulin Levels		Baseline (Screening) to Week 12
Change From Baseline in Testosterone (Free) Levels		Baseline (Screening) to Week 12
Change From Baseline in Testosterone (Total) Levels		Baseline (Screening) to Week 12
Change From Baseline in Urinary Symptoms		Baseline (Randomization) to Week 12

Collaborators and Investigators

• Sponsor: Shionogi
• Collaborators: Hormos Medical; QuatRx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 12, 2006

Study Record Updates

• Last Update Posted (Estimate): June 28, 2013
• Last Update Submitted That Met QC Criteria: May 21, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Menopausal symptoms; Urogenital atrophy; Vulvar and vaginal atrophy in postmenopausal women; Vaginal atrophy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Vaginal Diseases; Atrophy; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: 15-50310