Low-dose Hormone Therapy for Relief of Vasomotor Symptoms

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the lowest effective dose of the study drug for the relief of moderate to severe vasomotor symptoms in postmenopausal women for 12 weeks.

Detailed Description
-----------------
This study has previously been posted by Berlex, Inc. Berlex, Inc. has been renamed to Bayer HealthCare Pharmaceuticals, Inc. Bayer HealthCare Pharmaceuticals, Inc. is the sponsor of the trial.

Official Title
-----------------
A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Determine the Lowest Effective Dose of Combinations of Oral Drospirenone and 17 Beta-Estradiol for the Relief of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women Over a Treatment Period of 12 Weeks

Conditions
-----------------
Vasomotor Symptoms, Hot Flashes

Intervention / Treatment
-----------------
* Drug: 0.5mg DRSP / 0.5mg E2 (BAY86-4891)
* Drug: 0.25mg DRSP / 0.5mg E2 (BAY86-4891)
* Drug: Estradiol (E2 0.3mg)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Postmenopausal women >40 years of age experiencing a minimum of 7 to 8 moderate to severe hot flushes per day or 50 to 60 moderate to severe hot flushes per week Exclusion Criteria: The usual exclusion criteria for hormone therapy apply Intake of medications other than hormones affecting hot flushes

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5mg DRSP / 0.5mg E2 (BAY86-4891)<br>One tablet [0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle). | Drug: 0.5mg DRSP / 0.5mg E2 (BAY86-4891)<br>* One tablet [0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle).<br>|
| Experimental: 0.25mg DRSP / 0.5mg E2 (BAY86-4891)<br>One tablet [0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle). | Drug: 0.25mg DRSP / 0.5mg E2 (BAY86-4891)<br>* One tablet [0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle).<br>|
| Experimental: Estradiol (E2 0.3mg)<br>One tablet [17β-estradiol (E2 0.3mg)] per day taken orally for 3 cycles (28 days per cycle). | Drug: Estradiol (E2 0.3mg)<br>* One tablet [17β-estradiol (E2 0.3mg)] per day taken orally for 3 cycles (28 days per cycle).<br>|
| Placebo Comparator: Placebo<br>Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle). | Drug: Placebo<br>* Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 12 number of moderate to severe hot flushes minus baseline number. | Baseline until 12 weeks of treatment | 
| Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 4 number of moderate to severe hot flushes minus baseline number. | Baseline until 4 weeks of treatment | 
| Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 12 severity of moderate to severe hot flushes minus baseline severity. | Baseline until 12 weeks of treatment | 
| Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 4 severity of moderate to severe hot flushes minus baseline severity. | Baseline until 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Vaginal pH | Vaginal pH determined following speculum examination using vaginal pH paper and recorded on case report form (CRF). Absolute change calculated as week 12 pH minus baseline pH. | Baseline until 12 weeks of treatment | 
| Change From Baseline to Week 12 in Vaginal Maturation Value | Calculated as (percentage of superficial cells) + 0.5 * (percentage of intermediate cells). Absolute change calculated as week 12 value minus baseline value. | Baseline until 12 weeks of treatment | 
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | Subjects self-assessed symptom severity | After 12 weeks of treatment | 
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | Subjects self-assessed symptom severity | After 12 weeks of treatment | 
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | Subjects self-assessed symptom severity | After 12 weeks of treatment | 
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | Subjects self-assessed symptom severity | After 12 weeks of treatment | 
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | Subjects self-assessed symptom severity | After 12 weeks of treatment | 
| Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | Subjects self-assessed presence or absence of symptom | After 12 weeks of treatment | 
| Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | Subjects self-assessed presence or absence of symptom | After 12 weeks of treatment | 
| Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | Subjects self-assessed presence or absence of symptom; and if present recorded average number of times per night: 1; 2 to 4; more than 4. | After 12 weeks of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vasomotor symptom relief, Postmenopausal women, Severe to Moderate Vasomotor symptoms