Hot Flashes, Vasomotor Symptoms
Conditions
Keywords
Vasomotor symptom relief, Postmenopausal women, Severe to Moderate Vasomotor symptoms
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.
Interventions
DRUG0.5mg 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).
One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).
DRUGEstradiol (E2 0.3mg)
One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).
DRUGPlacebo
Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | Baseline until 4 weeks of treatment | 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. |
| Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | Baseline until 4 weeks of treatment | 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. |
| Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | Baseline until 12 weeks of treatment | 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. |
| Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | Baseline until 12 weeks of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | After 12 weeks of treatment | Subjects self-assessed symptom severity |
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | After 12 weeks of treatment | Subjects self-assessed symptom severity |
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | After 12 weeks of treatment | Subjects self-assessed symptom severity |
| Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | After 12 weeks of treatment | Subjects self-assessed presence or absence of symptom |
| Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | After 12 weeks of treatment | Subjects self-assessed presence or absence of symptom |
| Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | After 12 weeks of treatment | 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. |
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | After 12 weeks of treatment | Subjects self-assessed symptom severity |
| Change From Baseline to Week 12 in Vaginal pH | Baseline until 12 weeks of treatment | 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. |
| Change From Baseline to Week 12 in Vaginal Maturation Value | Baseline until 12 weeks of treatment | Calculated as (percentage of superficial cells) + 0.5 \* (percentage of intermediate cells). Absolute change calculated as week 12 value minus baseline value. |
| Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | After 12 weeks of treatment | Subjects self-assessed symptom severity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | Baseline until 12 weeks of treatment | 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. |
| Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | Baseline until 4 weeks of treatment | 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. |
| Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | Baseline until 12 weeks of treatment | 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. |
| Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | Baseline until 4 weeks of treatment | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 79 centers in the United States from 26 Mar 2007 (date of first participant's first visit) to 03 Nov 2008 (date of last participant's last visit)
Pre-assignment details
2457 Screened; 1722 Screen Failures; 735 randomized; 726 treated (Safety Analysis Set, SAF); 710 Full Analysis Set (FAS, randomized subjects with Baseline vasomotor symptom (VMS) data, took ≥1 study dose plus ≥1 VMS data day postdose); 569 Per Protocol Set (PPS, all subjects in FAS with ≥75% study drug compliance and no major protocol violations).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 178 |
| 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). | 177 |
| Estradiol (E2 0.3mg) One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle). | 179 |
| Placebo Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle). | 176 |
| Total | 710 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 | 6 | 4 |
| Overall Study | Hormone fear | 0 | 0 | 0 | 1 |
| Overall Study | In-/Exclusion criterion violated | 2 | 1 | 2 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 1 |
| Overall Study | Lost interest in study participation | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 5 | 2 | 6 |
| Overall Study | Move | 0 | 1 | 0 | 0 |
| Overall Study | Non-compliant with study drug | 1 | 0 | 5 | 0 |
| Overall Study | Non-compliant with visit schedule | 1 | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 2 | 1 | 3 |
| Overall Study | Randomization in Error | 2 | 0 | 1 | 1 |
| Overall Study | Site termination | 2 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 9 | 10 |
Baseline characteristics
| Characteristic | 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Estradiol (E2 0.3mg) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 5.61 | 53.5 years STANDARD_DEVIATION 5.77 | 53.3 years STANDARD_DEVIATION 6.05 | 53.4 years STANDARD_DEVIATION 6.46 | 53.5 years STANDARD_DEVIATION 5.97 |
| Body Mass Index (BMI) | 29.070 kg/sqm STANDARD_DEVIATION 6.0636 | 28.190 kg/sqm STANDARD_DEVIATION 5.6965 | 29.080 kg/sqm STANDARD_DEVIATION 5.741 | 27.882 kg/sqm STANDARD_DEVIATION 5.7859 | 28.543 kg/sqm STANDARD_DEVIATION 5.837 |
| Number of participants with hysterectomy/oophorectomy hysterectomized | 98 Participants | 91 Participants | 98 Participants | 99 Participants | 386 Participants |
| Number of participants with hysterectomy/oophorectomy oophorectomized | 61 Participants | 61 Participants | 63 Participants | 59 Participants | 244 Participants |
| Sex: Female, Male Female | 178 Participants | 177 Participants | 179 Participants | 176 Participants | 710 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Years since last menstruation at baseline | 9.913 years STANDARD_DEVIATION 8.6719 | 8.784 years STANDARD_DEVIATION 7.9947 | 9.214 years STANDARD_DEVIATION 8.1892 | 9.509 years STANDARD_DEVIATION 8.9693 | 9.355 years STANDARD_DEVIATION 8.456 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 80 / 181 | 75 / 183 | 68 / 182 | 64 / 180 |
| serious Total, serious adverse events | 0 / 181 | 1 / 183 | 3 / 182 | 1 / 180 |
Outcome results
Primary
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (Intention to Treat (ITT)) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -54.515 Hot Flushes per week |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -54.125 Hot Flushes per week |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -44.389 Hot Flushes per week |
| Placebo | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -30.020 Hot Flushes per week |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: 0.0005Wilcoxon/van Elteren
Primary
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -1.9294 Scores on a scale |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -1.000 Scores on a scale |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -0.2638 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -0.0698 Scores on a scale |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: 0.0096Wilcoxon/van Elteren
Primary
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.
Time frame: Baseline until 4 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -46.868 Hot Flushes per week |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -37.596 Hot Flushes per week |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -31.621 Hot Flushes per week |
| Placebo | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value) | -15.109 Hot Flushes per week |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/ van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the number of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Primary
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.
Time frame: Baseline until 4 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -0.2905 Scorese on a scale |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -0.1821 Scorese on a scale |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | -0.0651 Scorese on a scale |
| Placebo | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value) | 0.0000 Scorese on a scale |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 4 in the mean daily severity of hot flushes is identical in both arms, alternative: there is a shift in the distribution.p-value: 0.0005Wilcoxon/van Elteren
Secondary
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Vaginal Maturation Value | 10.07 Percentages of cells | Standard Deviation 28.638 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Vaginal Maturation Value | 11.71 Percentages of cells | Standard Deviation 29.185 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Vaginal Maturation Value | 7.69 Percentages of cells | Standard Deviation 25.627 |
| Placebo | Change From Baseline to Week 12 in Vaginal Maturation Value | -2.41 Percentages of cells | Standard Deviation 20.923 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal maturation value is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal maturation value is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal maturation value is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Secondary
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Vaginal pH | -0.63 (pH) | Standard Deviation 0.874 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Vaginal pH | -0.63 (pH) | Standard Deviation 0.935 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Vaginal pH | -0.66 (pH) | Standard Deviation 0.967 |
| Placebo | Change From Baseline to Week 12 in Vaginal pH | -0.06 (pH) | Standard Deviation 0.698 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal pH is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal pH is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Comparison: Comparison between E2 (0.3 mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The distribution of the change from baseline to week 12 in vaginal pH is identical in both arms, alternative: there is a shift in the distribution.p-value: <0.0001Wilcoxon/van Elteren
Secondary
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria'
Subjects self-assessed symptom severity
Time frame: After 12 weeks of treatment
Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | none | 166 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | mild | 6 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | moderate | 0 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | severe | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | severe | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | moderate | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | mild | 2 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | none | 169 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | moderate | 1 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | severe | 1 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | mild | 1 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | none | 167 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | severe | 0 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | none | 153 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | mild | 9 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' | moderate | 0 participants |
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.4397Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.0132Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.325Cochran-Mantel-Haenszel
Secondary
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching'
Subjects self-assessed symptom severity
Time frame: After 12 weeks of treatment
Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | none | 152 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | mild | 20 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | moderate | 0 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | severe | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | mild | 24 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | moderate | 3 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | severe | 4 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | none | 140 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | moderate | 5 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | mild | 21 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | severe | 0 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | none | 146 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | severe | 3 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | mild | 22 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | none | 128 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' | moderate | 11 participants |
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.0027Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.4463Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.0303Cochran-Mantel-Haenszel
Secondary
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity'
Subjects self-assessed symptom severity
Time frame: After 12 weeks of treatment
Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | none | 164 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | mild | 2 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | moderate | 0 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | severe | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | mild | 2 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | moderate | 1 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | severe | 0 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | none | 162 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | moderate | 0 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | mild | 3 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | severe | 0 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | none | 159 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | severe | 0 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | mild | 2 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | none | 151 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' | moderate | 0 participants |
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.8966Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.7512Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.8751Cochran-Mantel-Haenszel
Secondary
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness'
Subjects self-assessed symptom severity
Time frame: After 12 weeks of treatment
Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | none | 83 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | mild | 59 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | moderate | 24 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | severe | 6 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | mild | 52 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | moderate | 38 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | severe | 11 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | none | 70 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | moderate | 29 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | mild | 62 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | severe | 10 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | none | 71 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | severe | 12 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | mild | 47 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | none | 70 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' | moderate | 35 participants |
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.0314Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.878Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.5908Cochran-Mantel-Haenszel
Secondary
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity'
Subjects self-assessed symptom severity
Time frame: After 12 weeks of treatment
Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | none | 128 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | mild | 21 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | moderate | 13 participants |
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | severe | 4 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | mild | 22 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | moderate | 7 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | severe | 4 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | none | 132 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | moderate | 11 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | mild | 21 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | severe | 3 participants |
| Estradiol (E2 0.3mg) | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | none | 127 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | severe | 4 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | mild | 19 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | none | 118 participants |
| Placebo | Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' | moderate | 11 participants |
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.9555Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.1743Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebo on complete 2\*4 tablep-value: 0.4395Cochran-Mantel-Haenszel
Secondary
Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination'
Subjects self-assessed presence or absence of symptom
Time frame: After 12 weeks of treatment
Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | 45 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | 56 participants |
| Estradiol (E2 0.3mg) | Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | 62 participants |
| Placebo | Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination' | 57 participants |
Comparison: Comparison of active treatment arm with placebop-value: 0.1067Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.6011Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.4408Cochran-Mantel-Haenszel
Secondary
Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing'
Subjects self-assessed presence or absence of symptom
Time frame: After 12 weeks of treatment
Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | 70 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | 53 participants |
| Estradiol (E2 0.3mg) | Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | 53 participants |
| Placebo | Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing' | 48 participants |
Comparison: Comparison of active treatment arm with placebop-value: 0.0144Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.5589Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.55Cochran-Mantel-Haenszel
Secondary
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.
Time frame: After 12 weeks of treatment
Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | 99 participants |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | 114 participants |
| Estradiol (E2 0.3mg) | Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | 114 participants |
| Placebo | Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night' | 111 participants |
Comparison: Comparison of active treatment arm with placebop-value: 0.2179Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.7749Cochran-Mantel-Haenszel
Comparison: Comparison of active treatment arm with placebop-value: 0.8307Cochran-Mantel-Haenszel
Other Pre-specified
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -60.331 Hot Flushes per week | Standard Deviation 37.5217 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -55.317 Hot Flushes per week | Standard Deviation 30.2311 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -41.783 Hot Flushes per week | Standard Deviation 32.6122 |
| Placebo | Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -31.916 Hot Flushes per week | Standard Deviation 44.4507 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-33.2, -22]ANCOVA
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-27.8, -16.6]ANCOVA
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baselinep-value: 0.000795% CI: [-15.4, -4.2]ANCOVA
Other Pre-specified
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.
Time frame: Baseline until 12 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -1.4473 Scores on a scale | Standard Deviation 1.11616 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -1.2141 Scores on a scale | Standard Deviation 1.08299 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.7822 Scores on a scale | Standard Deviation 1.03497 |
| Placebo | Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.3873 Scores on a scale | Standard Deviation 0.7695 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-1.28, -0.859]ANCOVA
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-1.013, -0.593]ANCOVA
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 12 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: 0.000795% CI: [-0.57, -0.152]ANCOVA
Other Pre-specified
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.
Time frame: Baseline until 4 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -48.810 Hot Flushes per week | Standard Deviation 35.7876 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -38.989 Hot Flushes per week | Standard Deviation 27.7812 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -32.633 Hot Flushes per week | Standard Deviation 28.1349 |
| Placebo | Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value) | -24.195 Hot Flushes per week | Standard Deviation 54.748 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-29.9, 17.8]ANCOVA
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-20.2, -8.1]ANCOVA
Comparison: Comparison between E2 (0.3mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: 0.005495% CI: [-14.6, -2.5]ANCOVA
Other Pre-specified
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.
Time frame: Baseline until 4 weeks of treatment
Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.8347 scores on a scale | Standard Deviation 1.02226 |
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.5859 scores on a scale | Standard Deviation 0.89106 |
| Estradiol (E2 0.3mg) | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.4033 scores on a scale | Standard Deviation 0.73774 |
| Placebo | Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value) | -0.1926 scores on a scale | Standard Deviation 0.63585 |
Comparison: Comparison between DRSP/E2 (0.5mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-0.813, -0.458]ANCOVA
Comparison: Comparison between DRSP/E2 (0.25mg/0.5mg) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: <0.000195% CI: [-0.56, -0.205]ANCOVA
Comparison: Comparison between E2 (0.3) and Placebo with respect to a shift in the distribution of the end point. Null hypothesis: The mean change from baseline to week 4 is identical in both arms, alternative: there is a difference in the mean change from baseline.p-value: 0.023395% CI: [-0.381, -0.028]ANCOVA