Vasomotor Symptoms
Conditions
Keywords
Menopause, Hot Flush, Hot Flash, Desvenlafaxine succinate Sustained Release
Brief summary
The purpose of the study is to evaluate the efficacy and safety of Desvenlafaxine Succinate (DVS) Sustained Release (SR), in comparison to placebo for the treatment of Vasomotor Symptoms (VMS) in menopausal women.
Interventions
DRUGdesvenlafaxine succinate (DVS) SR
Titration with 50 mg tablets once daily for 7 days, then 100mg tablets once daily from day 8 to day 365, then taper with 50 mg tablets once daily for 7 days, followed by 25 mg tablets once daily for 7 days.
DRUGPlacebo
Titration with 50 mg placebo tablets once daily for 7 days, then 100mg placebo tablets once daily from day 8 to day 365, then taper with 50 mg placebo tablets once daily for 7 days, followed by 25 mg placebo tablets once daily for 7 days.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy, postmenopausal women who seek treatment for hot flushes * Body Mass Index (BMI) less than or equal to 34 kg/m\^2
Exclusion criteria
* Hypersensitivity to Venlafaxine * Myocardial infarction an/or unstable angina within 6 months of screening * History of seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Baseline up to Month 12 | Adjudicated ischemic cardiovascular events were a composite of: a) Coronary Heart Disease (CHD)-related death; b) New Myocardial Infarction (MI) (non-procedure-related MI); c) Documented new onset of unstable angina requiring hospitalization; d) Unscheduled coronary revascularization procedures (percutaneous coronary intervention) or bypass grafting. |
| Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12 | Baseline and Week 12 | Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes. |
| Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12 | Baseline and Week 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. |
| Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4 | Baseline and Week 4 | Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes. |
| Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4 | Baseline and Week 4 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | Baseline, Month 6 and Month 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. Adjusted mean was calculated by using change from baseline as response variable, treatment as factor, and baseline as covariate using the observed cases. |
| Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Baseline, Month 6 and Month 12 | Severity: mild (heat sensation without sweating); moderate (heat sensation with sweating; able to continue activity); severe (heat sensation with sweating; causing cessation of activity). Average daily severity of hot flushes= (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). Days with no hot flushes: severity score=0. As it was derived from count data, there was no maximum; minimum score=0; higher values= worse outcomes. Adjusted mean: calculated using change from baseline=response variable, treatment=factor and baseline=covariate using observed cases. |
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline and Week 12 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms. |
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Baseline and Month 6 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms. |
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Baseline and Month 12 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms. |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | Week 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | Month 6 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | Week 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | Month 6 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | Month 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | Week 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | Month 6 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | Month 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | Week 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | Month 6 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | Month 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | Month 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). |
| Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes | Baseline and Week 12 | A mean decrease from baseline of at least 5.35 moderate to severe hot flushes at week 12 in the participants was considered clinically meaningful. |
| Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Baseline, Week 4 and Week 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. |
| Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Baseline, Week 4 and Week 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. |
| Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes | Week 12 | Time to response was defined as the time-to-first 50% reduction in the average daily number of moderate to severe hot flushes over 3 consecutive days. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Baseline up to Month 12 | Adjudicated cerebrovascular events were identified using Standardized MedDRA Query (SMQ), for central nervous system haemorrhages and cerebrovascular conditions. Primary assessments included: 1) definite stroke, 2) probable stroke, 3) probable transient ischemic attack (TIA), and 4) no stroke or TIA. |
| Number of Participants With Hepatic Events | Baseline up to Month 12 | Hepatic events were defined as incidence of increased Liver Function Test (AST \[aspartate aminotransferase\] or ALT \[alanine aminotransferase\]) levels greater than 5 times the ULN (upper limit of normal). |
| Number of Participants With Ischemic Heart Disease | Baseline up to Month 12 | Potential ischaemic cardiac events were identified using the Standardized MedDRA Query (SMQ) Ischemic Heart Disease. |
| Number of Participants With Adjudicated Cerebrovascular Events - Probable TIA | Baseline up to Month 12 | Adjudicated cerebrovascular events were identified using Standardized MedDRA Query (SMQ), for central nervous system haemorrhages and cerebrovascular conditions. Primary assessments included: 1) definite stroke, 2) probable stroke, 3) probable transient ischemic attack (TIA), and 4) no stroke or TIA. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 3784 participants were screened, of which 1598 participants were screen failures and 2186 participants were randomly assigned to treatment.
Participants by arm
| Arm | Count |
|---|---|
| DVS SR 100 mg Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal. | 1,066 |
| Placebo Matching placebo tablets daily until Day 365 or early withdrawal. | 1,052 |
| Total | 2,118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 195 | 102 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 61 | 104 |
| Overall Study | Lost to Follow-up | 57 | 44 |
| Overall Study | Other | 5 | 2 |
| Overall Study | Protocol Violation | 13 | 16 |
| Overall Study | Randomized, not treated | 35 | 33 |
| Overall Study | Withdrawal by Subject | 66 | 64 |
Baseline characteristics
| Characteristic | Placebo | Total | DVS SR 100 mg |
|---|---|---|---|
| Age Continuous | 53.59 Years STANDARD_DEVIATION 4.91 | 53.77 Years STANDARD_DEVIATION 4.9 | 53.95 Years STANDARD_DEVIATION 4.9 |
| Daily number of moderate and severe hot flushes | 11.91 Hot Flushes STANDARD_DEVIATION 5.71 | 11.79 Hot Flushes STANDARD_DEVIATION 5.66 | 11.67 Hot Flushes STANDARD_DEVIATION 5.62 |
| Daily severity score of hot flushes | 2.39 Units on a scale STANDARD_DEVIATION 0.35 | 2.37 Units on a scale STANDARD_DEVIATION 0.34 | 2.36 Units on a scale STANDARD_DEVIATION 0.34 |
| Sex: Female, Male Female | 1052 Participants | 2118 Participants | 1066 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 941 / 1,066 | 872 / 1,052 |
| serious Total, serious adverse events | 43 / 1,066 | 36 / 1,052 |
Outcome results
Primary
Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12
The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity.
Time frame: Baseline and Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using last observation carried forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12 | -7.31 Hot Flushes | Standard Error 0.35 |
| Placebo | Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12 | -4.52 Hot Flushes | Standard Error 0.35 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided).p-value: <0.00195% CI: [-3.77, -1.82]ANCOVA
Primary
Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4
The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity.
Time frame: Baseline and Week 4
Population: Modified Intent-to-Treat(MITT) population: Participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks. Last observation carried forward (LOCF) method was used. 1 participant in each group did not have data till Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4 | -6.52 Hot Flushes | Standard Error 0.33 |
| Placebo | Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4 | -3.64 Hot Flushes | Standard Error 0.33 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided).p-value: <0.00195% CI: [-3.8, -1.98]ANCOVA
Primary
Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12
Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes.
Time frame: Baseline and Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using last observation carried forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12 | -0.59 Units on a Scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12 | -0.28 Units on a Scale | Standard Error 0.05 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided).p-value: <0.00195% CI: [-0.44, -0.18]ANCOVA
Primary
Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4
Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes.
Time frame: Baseline and Week 4
Population: MITT population: All participants randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using LOCF method. 1 participant in each group did not have data till Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4 | -0.47 Units on a Scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4 | -0.19 Units on a Scale | Standard Error 0.04 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided).p-value: <0.00195% CI: [-0.4, -0.16]ANCOVA
Primary
Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events
Adjudicated ischemic cardiovascular events were a composite of: a) Coronary Heart Disease (CHD)-related death; b) New Myocardial Infarction (MI) (non-procedure-related MI); c) Documented new onset of unstable angina requiring hospitalization; d) Unscheduled coronary revascularization procedures (percutaneous coronary intervention) or bypass grafting.
Time frame: Baseline up to Month 12
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | CHD related death | 0 Participants |
| DVS SR 100 mg | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | New Onset of Unstable Angina | 0 Participants |
| DVS SR 100 mg | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | New MI | 0 Participants |
| DVS SR 100 mg | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Unscheduled Coronary Revascularization Procedures | 0 Participants |
| DVS SR 100 mg | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Any ischemic CV event | 0 Participants |
| Placebo | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Unscheduled Coronary Revascularization Procedures | 0 Participants |
| Placebo | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Any ischemic CV event | 1 Participants |
| Placebo | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | CHD related death | 0 Participants |
| Placebo | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | New MI | 1 Participants |
| Placebo | Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | New Onset of Unstable Angina | 0 Participants |
Comparison: Excess risk of DVS SR 100 mg over placebo per 1000 woman-years of exposure, defined as the difference in the exposure adjusted rates between the treatment groups, was obtained.90% CI: [-2.86, 0.72]
Secondary
Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12
Severity: mild (heat sensation without sweating); moderate (heat sensation with sweating; able to continue activity); severe (heat sensation with sweating; causing cessation of activity). Average daily severity of hot flushes= (1\*Number of mild+2\*Number of moderate+3\*Number of severe)/(Total number of hot flushes). Days with no hot flushes: severity score=0. As it was derived from count data, there was no maximum; minimum score=0; higher values= worse outcomes. Adjusted mean: calculated using change from baseline=response variable, treatment=factor and baseline=covariate using observed cases.
Time frame: Baseline, Month 6 and Month 12
Population: MITT participants of the efficacy sub-study population who had non-missing average daily number of moderate and severe hot flushes. The assessment was done using observed values. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Month 6 (n= 125, 124) | -0.87 Units on a Scale | Standard Error 0.07 |
| DVS SR 100 mg | Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Month 12 (n= 112, 102) | -0.78 Units on a Scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Month 6 (n= 125, 124) | -0.56 Units on a Scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Month 12 (n= 112, 102) | -0.45 Units on a Scale | Standard Error 0.08 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided). (At month 6)p-value: 0.00295% CI: [-0.51, -0.12]ANCOVA
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided). (At month 12)p-value: 0.00395% CI: [-0.54, -0.11]ANCOVA
Secondary
Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12
The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. Adjusted mean was calculated by using change from baseline as response variable, treatment as factor, and baseline as covariate using the observed cases.
Time frame: Baseline, Month 6 and Month 12
Population: MITT participants of the efficacy sub-study population who had non-missing average daily number of moderate and severe hot flushes. The assessment was done using observed values. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | Month 6 (n= 125, 124) | -8.65 Hot Flushes | Standard Error 0.37 |
| DVS SR 100 mg | Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | Month 12 (n= 112, 102) | -7.98 Hot Flushes | Standard Error 0.46 |
| Placebo | Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | Month 6 (n= 125, 124) | -6.61 Hot Flushes | Standard Error 0.37 |
| Placebo | Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | Month 12 (n= 112, 102) | -5.17 Hot Flushes | Standard Error 0.48 |
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided). (At month 6)p-value: <0.00195% CI: [-3.07, -1]ANCOVA
Comparison: An analysis of covariance with treatment as factor and baseline value as a covariate was used to compare DVS SR 100 mg with matching placebo. The comparison was performed at significance level of p=0.05 (two sided). (At month 12)p-value: <0.00195% CI: [-4.12, -1.51]ANCOVA
Secondary
Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12
GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms.
Time frame: Baseline and Month 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Depression Scale | -2.66 Units on a Scale | Standard Error 0.08 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Psychological Scale | -5.88 Units on a Scale | Standard Error 0.16 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Anxiety Scale | -3.25 Units on a Scale | Standard Error 0.09 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Somatic Scale | -1.63 Units on a Scale | Standard Error 0.09 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Sexual Dysfunction Scale | -0.51 Units on a Scale | Standard Error 0.03 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Vasomotor Scale | -2.64 Units on a Scale | Standard Error 0.06 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Total Score | -10.60 Units on a Scale | Standard Error 0.26 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Vasomotor Scale | -2.19 Units on a Scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Total Score | -8.89 Units on a Scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Anxiety Scale | -2.69 Units on a Scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Depression Scale | -2.04 Units on a Scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Sexual Dysfunction Scale | -0.43 Units on a Scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Psychological Scale | -4.70 Units on a Scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | Somatic Scale | -1.61 Units on a Scale | Standard Error 0.08 |
Comparison: For Month 12: Change from baseline of the GCS Total score was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-2.42, -1]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Anxiety scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.81, -0.3]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Depression scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.83, -0.4]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Sexual Dysfunction scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.08295% CI: [-0.17, 0.01]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Psychological scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-1.61, -0.75]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Somatic scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.86595% CI: [-0.25, 0.21]Mixed Models Analysis
Comparison: For Month 12: Change from baseline of the GCS Vasomotor scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6 and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.61, -0.29]Mixed Models Analysis
Secondary
Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6
GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms.
Time frame: Baseline and Month 6
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Anxiety Scale | -3.06 Units on a Scale | Standard Error 0.09 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Sexual Dysfunction Scale | -0.46 Units on a Scale | Standard Error 0.03 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Total Score | -9.84 Units on a Scale | Standard Error 0.25 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Depression Scale | -2.35 Units on a Scale | Standard Error 0.08 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Psychological Scale | -5.39 Units on a Scale | Standard Error 0.15 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Somatic Scale | -1.49 Units on a Scale | Standard Error 0.08 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Vasomotor Scale | -2.55 Units on a Scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Vasomotor Scale | -2.14 Units on a Scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Depression Scale | -1.77 Units on a Scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Sexual Dysfunction Scale | -0.41 Units on a Scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Psychological Scale | -4.15 Units on a Scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Somatic Scale | -1.31 Units on a Scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Total Score | -7.97 Units on a Scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | Anxiety Scale | -2.41 Units on a Scale | Standard Error 0.09 |
Comparison: For Month 6: Change from baseline of the GCS Total score was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-2.57, -1.18]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Anxiety scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.9, -0.41]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Depression scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.8, -0.37]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Sexual Dysfunction scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.28295% CI: [-0.13, 0.04]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Psychological scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-1.66, -0.82]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Somatic scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.1495% CI: [-0.41, 0.06]Mixed Models Analysis
Comparison: For Month 6: Change from baseline of the GCS Vasomotor scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.56, -0.26]Mixed Models Analysis
Secondary
Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12
GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms \[range 0-33\], anxiety \[range 0-18\], depression \[range 0-15\], somatic symptoms \[range 0-21\], vasomotor symptoms \[range 0-6\], and sexual dysfunction \[range 0-3\]). A decrease in the total climacteric score indicated an improvement in symptoms.
Time frame: Baseline and Week 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy Greene Climacteric Scale (GCS) assessment or at least 1 on therapy Patient Global Impression (PGI) assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Somatic Scale | 4.54 Units on a Scale | Standard Error 0.11 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Total Score | 22.48 Units on a Scale | Standard Error 0.28 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Anxiety Scale | 6.43 Units on a Scale | Standard Error 0.1 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Depression Scale | 4.92 Units on a Scale | Standard Error 0.1 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Sexual Dysfunction Scale | 1.60 Units on a Scale | Standard Error 0.03 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Psychological Scale | 11.35 Units on a Scale | Standard Error 0.18 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Vasomotor Scale | 4.99 Units on a Scale | Standard Error 0.04 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Total Score | -9.18 Units on a Scale | Standard Error 0.25 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Anxiety Scale | -2.81 Units on a Scale | Standard Error 0.09 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Depression Scale | -2.23 Units on a Scale | Standard Error 0.08 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Sexual Dysfunction Scale | -0.41 Units on a Scale | Standard Error 0.03 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Psychological Scale | -5.04 Units on a Scale | Standard Error 0.15 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Somatic Scale | -1.24 Units on a Scale | Standard Error 0.09 |
| DVS SR 100 mg | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Vasomotor Scale | -2.50 Units on a Scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Sexual Dysfunction Scale | -0.36 Units on a Scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Total Score | -6.84 Units on a Scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Total Score | 22.04 Units on a Scale | Standard Error 0.28 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Somatic Scale | -1.02 Units on a Scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Anxiety Scale | 6.36 Units on a Scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Anxiety Scale | -2.06 Units on a Scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Depression Scale | 4.84 Units on a Scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Psychological Scale | -3.62 Units on a Scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Sexual Dysfunction Scale | 1.65 Units on a Scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Depression Scale | -1.55 Units on a Scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Psychological Scale | 11.19 Units on a Scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Somatic Scale | 4.21 Units on a Scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Week 12: Vasomotor Scale | -1.85 Units on a Scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | Baseline: Vasomotor Scale | 4.99 Units on a Scale | Standard Error 0.04 |
Comparison: For Week 12: Change from baseline of the GCS Total score was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-3.05, -1.64]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Anxiety scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.99, -0.51]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Depression scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.89, -0.45]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Sexual Dysfunction scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.16295% CI: [-0.13, 0.02]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Psychological scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 was outcome variable, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-1.84, -1]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Somatic scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: 0.06695% CI: [-0.46, 0.01]Mixed Models Analysis
Comparison: For Week 12: Change from baseline of the GCS Vasomotor scale subscore was analyzed using a Mixed-effects model repeated measures (MMRM), for which changes from baseline at week 12, month 6, and month 12 were outcome variables, with treatment, week, and interaction between treatment and week as fixed effects with participant as a random effect, and with the baseline score as covariate.p-value: <0.00195% CI: [-0.79, -0.5]Mixed Models Analysis
Secondary
Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes
Time to response was defined as the time-to-first 50% reduction in the average daily number of moderate to severe hot flushes over 3 consecutive days.
Time frame: Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DVS SR 100 mg | Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes | 13.0 Days |
| Placebo | Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes | 48.0 Days |
Comparison: A log-rank test was used to compare the treatment groups.p-value: <0.001Log Rank
Secondary
Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes
A mean decrease from baseline of at least 5.35 moderate to severe hot flushes at week 12 in the participants was considered clinically meaningful.
Time frame: Baseline and Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using last observation carried forward (LOCF) method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DVS SR 100 mg | Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes | 117 Participants |
| Placebo | Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes | 75 Participants |
Comparison: The proportion of participants achieving a response as defined by minimal clinically important difference (MCID) at week 12 was compared between DVS and placebo treatment groups with a Cochran-Mantel-Haenszel test.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes
The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity.
Time frame: Baseline, Week 4 and Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using last observation carried forward (LOCF) method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 4 | 58.47 Percentage of participants |
| DVS SR 100 mg | Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 12 | 67.93 Percentage of participants |
| Placebo | Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 4 | 28.89 Percentage of participants |
| Placebo | Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 12 | 44.20 Percentage of participants |
Comparison: The proportion of participants achieving at least 50% hot flush reduction from baseline at 4-week was compared between DVS and placebo treatment groups with a logistic regression model with treatment as factor and baseline value as a covariate.p-value: <0.00195% CI: [2.24, 5.36]Regression, Logistic
Comparison: The proportion of participants achieving at least 50% hot flush reduction from baseline at 12-week was compared between DVS and placebo treatment groups with a logistic regression model with treatment as factor and baseline value as a covariate.p-value: <0.00195% CI: [1.75, 4.1]Regression, Logistic
Secondary
Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes
The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity.
Time frame: Baseline, Week 4 and Week 12
Population: MITT population included all participants who were randomized into efficacy substudy, had at least 1 dose of study drug, had vasomotor symptoms recorded on at least 1 day of baseline period and at least 1 day of on-therapy period during initial 12 weeks of therapy. Assessment was done using last observation carried forward (LOCF) method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 4 | 32.79 Percentage of participants |
| DVS SR 100 mg | Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 12 | 41.30 Percentage of participants |
| Placebo | Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 4 | 10.00 Percentage of participants |
| Placebo | Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | Week 12 | 18.23 Percentage of participants |
Comparison: The proportion of participants achieving at least 75% hot flush reduction from baseline at 4-week was compared between DVS and placebo treatment groups with a logistic regression model with treatment as factor and baseline value as a covariate.p-value: <0.00195% CI: [2.47, 7.81]Regression, Logistic
Comparison: The proportion of participants achieving at least 75% hot flush reduction from baseline at 12-week was compared between DVS and placebo treatment groups with a logistic regression model with treatment as factor and baseline value as a covariate.p-value: <0.00195% CI: [1.96, 5.09]Regression, Logistic
Secondary
Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Month 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 2= Much Improved | 29.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 5= Minimally Worse | 2.4 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 3= Minimally Improved | 21.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 6= Much Worse | 2.7 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 1= Very Much Improved | 31.0 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 7= Very Much Worse | 0.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 4= No Change | 12.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 7= Very Much Worse | 0.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 2= Much Improved | 24.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 3= Minimally Improved | 21.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 4= No Change | 26.8 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 5= Minimally Worse | 4.4 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 6= Much Worse | 2.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | 1= Very Much Improved | 19.9 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Month 12
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 3= Minimally Improved | 21.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 5= Minimally Worse | 1.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 2= Much Improved | 24.4 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 6= Much Worse | 4.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 4= No Change | 10.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 7= Very Much Worse | 1.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 1= Very Much Improved | 37.2 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 7= Very Much Worse | 0.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 1= Very Much Improved | 13.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 2= Much Improved | 18.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 3= Minimally Improved | 25.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 4= No Change | 36.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 5= Minimally Worse | 5.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | 6= Much Worse | 1.7 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Month 6
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 2= Much Improved | 32.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 5= Minimally Worse | 3.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 4= No Change | 11.6 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 6= Much Worse | 2.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 3= Minimally Improved | 20.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 7= Very Much Worse | 1.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 1= Very Much Improved | 28.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 7= Very Much Worse | 0.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 1= Very Much Improved | 17.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 3= Minimally Improved | 20.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 2= Much Improved | 27.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 4= No Change | 26.2 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 5= Minimally Worse | 5.2 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | 6= Much Worse | 2.6 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Week 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 6= Much Worse | 2.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 4= No Change | 11.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 2= Much Improved | 32.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 5= Minimally Worse | 4.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 1= Very Much Improved | 25.8 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 7= Very Much Worse | 0.8 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 3= Minimally Improved | 23.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 7= Very Much Worse | 0.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 1= Very Much Improved | 13.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 2= Much Improved | 25.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 3= Minimally Improved | 25.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 4= No Change | 29.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 6= Much Worse | 1.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | 5= Minimally Worse | 4.5 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Month 6
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 3= Minimally Improved | 15.7 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 4= No Change | 11.0 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 5= Minimally Worse | 2.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 6= Much Worse | 2.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 2= Much Improved | 32.6 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 7= Very Much Worse | 0.6 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 1= Very Much Improved | 34.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 7= Very Much Worse | 0.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 5= Minimally Worse | 4.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 1= Very Much Improved | 14.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 2= Much Improved | 25.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 4= No Change | 29.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 6= Much Worse | 2.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | 3= Minimally Improved | 23.4 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12
PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Week 12
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 3= Minimally Improved | 17.4 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 5= Minimally Worse | 2.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 2= Much Improved | 35.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 6= Much Worse | 3.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 4= No Change | 12.8 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 7= Very Much Worse | 1.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 1= Very Much Improved | 26.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 7= Very Much Worse | 0.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 1= Very Much Improved | 7.4 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 2= Much Improved | 22.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 3= Minimally Improved | 29.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 4= No Change | 34.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 5= Minimally Worse | 4.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | 6= Much Worse | 1.7 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Month 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 2= Minimal | 32.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 4= Moderate | 21.6 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 3= Mild | 25.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 5= Severe | 10.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 1= None | 10.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 5= Severe | 14.4 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 1= None | 7.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 2= Minimal | 27.8 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 3= Mild | 21.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | 4= Moderate | 29.7 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Month 6
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 2= Minimal | 32.2 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 4= Moderate | 22.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 3= Mild | 27.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 5= Severe | 9.0 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 1= None | 8.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 5= Severe | 14.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 1= None | 5.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 2= Minimal | 25.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 3= Mild | 23.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | 4= Moderate | 31.1 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Week 12
Population: Main study efficacy population included all participants who were randomized; had at least 1 dose of study medication; and had a baseline and at least 1 on therapy GCS assessment or at least 1 on therapy PGI assessment. Assessment was done using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 2= Minimal | 27.8 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 4= Moderate | 24.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 3= Mild | 28.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 5= Severe | 9.6 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 1= None | 8.8 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 5= Severe | 16.2 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 1= None | 5.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 2= Minimal | 18.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 3= Mild | 26.5 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | 4= Moderate | 33.8 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Month 12
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 5= Severe | 17.4 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 1= None | 9.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 2= Minimal | 28.5 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 3= Mild | 26.7 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 4= Moderate | 18.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 4= Moderate | 39.4 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 3= Mild | 12.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 1= None | 4.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 5= Severe | 26.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | 2= Minimal | 17.1 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Month 6
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 2= Minimal | 29.7 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 4= Moderate | 16.9 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 3= Mild | 27.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 5= Severe | 14.0 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 1= None | 12.2 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 5= Severe | 26.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 1= None | 2.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 2= Minimal | 18.3 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 3= Mild | 17.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | 4= Moderate | 34.3 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12
PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe).
Time frame: Week 12
Population: MITT population: All participants randomized into efficacy substudy; at least 1 dose of study drug, vasomotor symptoms recorded on at least 1 day of baseline period and 1 day of on-therapy period during initial 12 weeks of therapy. LOCF method was used. Participants analyzed included those who were evaluated for this particular scale.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 2= Minimal | 20.3 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 4= Moderate | 24.4 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 3= Mild | 29.1 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 5= Severe | 18.0 Percentage of Participants |
| DVS SR 100 mg | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 1= None | 8.1 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 5= Severe | 28.0 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 1= None | 1.7 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 2= Minimal | 10.9 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 3= Mild | 16.6 Percentage of Participants |
| Placebo | Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | 4= Moderate | 42.9 Percentage of Participants |
Comparison: A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.p-value: <0.001Cochran-Mantel-Haenszel
Other Pre-specified
Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke
Adjudicated cerebrovascular events were identified using Standardized MedDRA Query (SMQ), for central nervous system haemorrhages and cerebrovascular conditions. Primary assessments included: 1) definite stroke, 2) probable stroke, 3) probable transient ischemic attack (TIA), and 4) no stroke or TIA.
Time frame: Baseline up to Month 12
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR 100 mg | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Any Stroke (Definite or Probable) | 1 Participants |
| DVS SR 100 mg | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Definite Stroke | 0 Participants |
| DVS SR 100 mg | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Probable Stroke | 1 Participants |
| Placebo | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Any Stroke (Definite or Probable) | 0 Participants |
| Placebo | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Definite Stroke | 0 Participants |
| Placebo | Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke | Probable Stroke | 0 Participants |
Comparison: Excess risk over placebo of DVS SR 100 mg per 1000 woman-years of exposure, defined as the difference in the exposure adjusted rates between the treatment groups, was obtained.90% CI: [-0.68, 2.9]
Other Pre-specified
Number of Participants With Adjudicated Cerebrovascular Events - Probable TIA
Adjudicated cerebrovascular events were identified using Standardized MedDRA Query (SMQ), for central nervous system haemorrhages and cerebrovascular conditions. Primary assessments included: 1) definite stroke, 2) probable stroke, 3) probable transient ischemic attack (TIA), and 4) no stroke or TIA.
Time frame: Baseline up to Month 12
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DVS SR 100 mg | Number of Participants With Adjudicated Cerebrovascular Events - Probable TIA | 1 Participants |
| Placebo | Number of Participants With Adjudicated Cerebrovascular Events - Probable TIA | 0 Participants |
Other Pre-specified
Number of Participants With Hepatic Events
Hepatic events were defined as incidence of increased Liver Function Test (AST \[aspartate aminotransferase\] or ALT \[alanine aminotransferase\]) levels greater than 5 times the ULN (upper limit of normal).
Time frame: Baseline up to Month 12
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DVS SR 100 mg | Number of Participants With Hepatic Events | 2 Participants |
| Placebo | Number of Participants With Hepatic Events | 2 Participants |
Comparison: Excess risk over placebo of DVS SR 100 mg per 1000 woman-years of exposure, defined as the difference in the exposure adjusted rates between the treatment groups, was obtained.90% CI: [-3.51, 3.67]
Other Pre-specified
Number of Participants With Ischemic Heart Disease
Potential ischaemic cardiac events were identified using the Standardized MedDRA Query (SMQ) Ischemic Heart Disease.
Time frame: Baseline up to Month 12
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DVS SR 100 mg | Number of Participants With Ischemic Heart Disease | 4 Participants |
| Placebo | Number of Participants With Ischemic Heart Disease | 2 Participants |
Comparison: Excess risk over placebo of DVS SR 100 mg per 1000 woman-years of exposure, defined as the difference in the exposure adjusted rates between the treatment groups, was obtained.90% CI: [-2.08, 6.71]