Low-dose Hormone Therapy for Relief of Vasomotor Symptoms

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

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.

Study Overview

• Status: Completed
• 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

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.

• Study Type: Interventional
• Enrollment (Actual): 735
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Chandler, Arizona, United States, 85225
    • Phoenix, Arizona, United States, 85031
    • Tucson, Arizona, United States, 85712
    • Tucson, Arizona, United States, 85741
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Paramount, California, United States, 90723
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92108
    • San Diego, California, United States, 92123
    • San Diego, California, United States, 92121
    • Valley Village, California, United States, 91607
    • Vista, California, United States, 92083
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
    • Denver, Colorado, United States, 80218
  • Connecticut
    • New Britain, Connecticut, United States, 06050
  • Florida
    • Boynton Beach, Florida, United States, 33437
    • Clearwater, Florida, United States, 33761
    • Daytona Beach, Florida, United States, 32114
    • Fort Myers, Florida, United States, 33916
    • Jacksonville, Florida, United States, 32216
    • Lake Worth, Florida, United States, 33461
    • Leesburg, Florida, United States, 34748
    • Miami, Florida, United States, 33186
    • Miami, Florida, United States, 33169
    • New Port Richey, Florida, United States, 34655
    • Tampa, Florida, United States, 33607
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Atlanta, Georgia, United States, 30342
    • Atlanta, Georgia, United States, 30328
    • Decatur, Georgia, United States, 30034
  • Idaho
    • Boise, Idaho, United States, 83702
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Arlington Heights, Illinois, United States, 60004
    • Champaign, Illinois, United States, 61820
    • La Grange Park, Illinois, United States, 60526
  • Indiana
    • Newburgh, Indiana, United States, 47630
  • Kentucky
    • Lexington, Kentucky, United States, 40536
  • Louisiana
    • Amite, Louisiana, United States, 70422
    • Marrero, Louisiana, United States, 70072
  • Michigan
    • Paw Paw, Michigan, United States, 49079
  • Minnesota
    • Chaska, Minnesota, United States, 55318
  • Missouri
    • Springfield, Missouri, United States, 65802
  • Montana
    • Billings, Montana, United States, 59101
    • Billings, Montana, United States, 59102
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States, 89104
    • Reno, Nevada, United States, 89502
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
    • New Brunswick, New Jersey, United States, 08901
    • Princeton, New Jersey, United States, 08540
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
    • Winston-Salem, North Carolina, United States, 27103
  • North Dakota
    • Fargo, North Dakota, United States, 58105
  • Ohio
    • Cleveland, Ohio, United States, 44122
    • Columbus, Ohio, United States, 43213
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
    • Tulsa, Oklahoma, United States, 74105
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16502
    • Philadelphia, Pennsylvania, United States, 19114
    • Pittsburgh, Pennsylvania, United States, 15206
    • Wexford, Pennsylvania, United States, 15090
  • South Carolina
    • Columbia, South Carolina, United States, 29201
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
    • Chattanooga, Tennessee, United States, 37403
    • Memphis, Tennessee, United States, 38120
  • Texas
    • Dallas, Texas, United States, 75234
    • Houston, Texas, United States, 77030
    • Houston, Texas, United States, 77004
  • Vermont
    • Burlington, Vermont, United States, 05401
  • Virginia
    • Norfolk, Virginia, United States, 23507
    • Richmond, Virginia, United States, 23294
  • Washington
    • Renton, Washington, United States, 98055
    • Seattle, Washington, United States, 98105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

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: 0.5mg DRSP / 0.5mg E2 (BAY86-4891); 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); One tablet [0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle).
Experimental: 0.25mg DRSP / 0.5mg E2 (BAY86-4891); 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); One tablet [0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)] per day taken orally for 3 cycles (28 days per cycle).
Experimental: Estradiol (E2 0.3mg); One tablet [17β-estradiol (E2 0.3mg)] per day taken orally for 3 cycles (28 days per cycle).	Drug: Estradiol (E2 0.3mg); One tablet [17β-estradiol (E2 0.3mg)] per day taken orally for 3 cycles (28 days per cycle).
Placebo Comparator: Placebo; Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).	Drug: Placebo; Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean 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 (Mean 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 (Mean 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 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 (Mean 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 moderate to severe hot flushes minus baseline severity.	Baseline until 4 weeks of treatment

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Sutter G, Schmelter T, Gude K, Schaefers M, Gerlinger C, Archer DF. Population pharmacokinetic/pharmacodynamic evaluation of low-dose drospirenone with 17beta-estradiol in postmenopausal women with moderate to severe vasomotor symptoms. Menopause. 2014 Mar;21(3):236-42. doi: 10.1097/GME.0b013e31829c12e8.
• Archer DF, Schmelter T, Schaefers M, Gerlinger C, Gude K. A randomized, double-blind, placebo-controlled study of the lowest effective dose of drospirenone with 17beta-estradiol for moderate to severe vasomotor symptoms in postmenopausal women. Menopause. 2014 Mar;21(3):227-35. doi: 10.1097/GME.0b013e31829c1431.
• K. Gude; T. Schmelter; M. Schaefers; C. Gerlinger. Efficacy of low dose Angeliq (0.5 mg E2 and 0.25 or 0.5 mg DRSP) compared to Angeliq (1 mg E2 and 1, 2 or 3 mg DRSP) in postmenopausal women with moderate to severe hot flushes. Menopause, Vol. 19, No. 12, 2012 * 2012, P-36, p 1388
• Gerlinger C, Gude K, Hiemeyer F, Schmelter T, Schafers M. An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women. Menopause. 2012 Jul;19(7):799-803. doi: 10.1097/gme.0b013e31823de8ba.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: March 9, 2007
• First Submitted That Met QC Criteria: March 9, 2007
• First Posted (Estimate): March 12, 2007

Study Record Updates

• Last Update Posted (Estimate): May 6, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Postmenopausal women; Vasomotor symptom relief; Severe to Moderate Vasomotor symptoms
• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Estradiol; Drospirenone
• Other Study ID Numbers: 91493; 310184 (Other Identifier: Company internal)