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Trial record 33 of 89 for:    DESVENLAFAXINE

Study Evaluating The Safety And Efficacy Of Desvenlafaxine Succinate For Vasomotor Symptoms In Menopausal Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00683800
Recruitment Status : Completed
First Posted : May 23, 2008
Results First Posted : August 17, 2011
Last Update Posted : August 17, 2011
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Vasomotor Symptoms
Interventions Drug: desvenlafaxine succinate (DVS) SR
Drug: Placebo
Enrollment 2186
Recruitment Details  
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.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal. Matching placebo tablets daily until Day 365 or early withdrawal.
Period Title: Overall Study
Started 1101 1085
Treated 1066 1052
Completed 669 719
Not Completed 432 366
Reason Not Completed
Adverse Event             195             102
Death             0             1
Lost to Follow-up             57             44
Other             5             2
Protocol Violation             13             16
Withdrawal by Subject             66             64
Lack of Efficacy             61             104
Randomized, not treated             35             33
Arm/Group Title DVS SR 100 mg Placebo Total
Hide Arm/Group Description Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal. Matching placebo tablets daily until Day 365 or early withdrawal. Total of all reporting groups
Overall Number of Baseline Participants 1066 1052 2118
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1066 participants 1052 participants 2118 participants
53.95  (4.90) 53.59  (4.91) 53.77  (4.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1066 participants 1052 participants 2118 participants
Female
1066
 100.0%
1052
 100.0%
2118
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Daily number of moderate and severe hot flushes   [1] 
Mean (Standard Deviation)
Unit of measure:  Hot Flushes
Number Analyzed 1066 participants 1052 participants 2118 participants
11.67  (5.62) 11.91  (5.71) 11.79  (5.66)
[1]
Measure Description: Average daily number of moderate and severe hot flushes was calculated as the sum of number of moderate and severe hot flushes on each day divided by number of days with data. Moderate: sensation of heat with sweating; able to continue activity; and severe: sensation of heat with sweating; causing cessation of activity. Participants analysed were 184 and 181 for DVS SR 100 mg group and placebo group, respectively.
Daily severity score of hot flushes   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 1066 participants 1052 participants 2118 participants
2.36  (0.34) 2.39  (0.35) 2.37  (0.34)
[1]
Measure Description: Severity: 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). 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 days with no hot flushes, severity score was set as 0. As this was derived from count data, there was no maximum; minimum score was 0; the higher values showed worse outcomes. n=184 (DVS SR 100 mg group); n=181 (placebo group).
1.Primary Outcome
Title Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 183 180
Mean (Standard Error)
Unit of Measure: Hot Flushes
-6.52  (0.33) -3.64  (0.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -2.89
Confidence Interval (2-Sided) 95%
-3.80 to -1.98
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Mean (Standard Error)
Unit of Measure: Hot Flushes
-7.31  (0.35) -4.52  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -2.79
Confidence Interval (2-Sided) 95%
-3.77 to -1.82
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 183 180
Mean (Standard Error)
Unit of Measure: Units on a Scale
-0.47  (0.04) -0.19  (0.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.40 to -0.16
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Mean (Standard Error)
Unit of Measure: Units on a Scale
-0.59  (0.05) -0.28  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.44 to -0.18
Estimation Comments [Not Specified]
5.Primary Outcome
Title Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study medication.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 1066 1052
Measure Type: Number
Unit of Measure: Participants
Any ischemic CV event 0 1
CHD related death 0 0
New MI 0 1
New Onset of Unstable Angina 0 0
Unscheduled Coronary Revascularization Procedures 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Wald Formula
Estimated Value -1.07
Confidence Interval (2-Sided) 90%
-2.86 to 0.72
Estimation Comments The 90% CI for excess risk was obtained using the Wald Formula.
6.Secondary Outcome
Title Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: Participants
117 75
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: Percentage of participants
Week 4 58.47 28.89
Week 12 67.93 44.20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.47
Confidence Interval (2-Sided) 95%
2.24 to 5.36
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.67
Confidence Interval (2-Sided) 95%
1.75 to 4.10
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: Percentage of participants
Week 4 32.79 10.00
Week 12 41.30 18.23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.39
Confidence Interval (2-Sided) 95%
2.47 to 7.81
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.16
Confidence Interval (2-Sided) 95%
1.96 to 5.09
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Median (95% Confidence Interval)
Unit of Measure: Days
13.0
(10.0 to 18.0)
48.0
(32.0 to 64.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A log-rank test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Mean (Standard Error)
Unit of Measure: Hot Flushes
Month 6 (n= 125, 124) -8.65  (0.37) -6.61  (0.37)
Month 12 (n= 112, 102) -7.98  (0.46) -5.17  (0.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -2.04
Confidence Interval (2-Sided) 95%
-3.07 to -1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -2.81
Confidence Interval (2-Sided) 95%
-4.12 to -1.51
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 184 181
Mean (Standard Error)
Unit of Measure: Units on a Scale
Month 6 (n= 125, 124) -0.87  (0.07) -0.56  (0.07)
Month 12 (n= 112, 102) -0.78  (0.07) -0.45  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.51 to -0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.54 to -0.11
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 964 986
Mean (Standard Error)
Unit of Measure: Units on a Scale
Baseline: Total Score 22.48  (0.28) 22.04  (0.28)
Baseline: Anxiety Scale 6.43  (0.10) 6.36  (0.10)
Baseline: Depression Scale 4.92  (0.10) 4.84  (0.09)
Baseline: Sexual Dysfunction Scale 1.60  (0.03) 1.65  (0.03)
Baseline: Psychological Scale 11.35  (0.18) 11.19  (0.18)
Baseline: Somatic Scale 4.54  (0.11) 4.21  (0.11)
Baseline: Vasomotor Scale 4.99  (0.04) 4.99  (0.04)
Week 12: Total Score -9.18  (0.25) -6.84  (0.25)
Week 12: Anxiety Scale -2.81  (0.09) -2.06  (0.09)
Week 12: Depression Scale -2.23  (0.08) -1.55  (0.08)
Week 12: Sexual Dysfunction Scale -0.41  (0.03) -0.36  (0.03)
Week 12: Psychological Scale -5.04  (0.15) -3.62  (0.15)
Week 12: Somatic Scale -1.24  (0.09) -1.02  (0.09)
Week 12: Vasomotor Scale -2.50  (0.05) -1.85  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-3.05 to -1.64
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.75
Confidence Interval (2-Sided) 95%
-0.99 to -0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-0.89 to -0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-1.84 to -1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.46 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-0.79 to -0.50
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 796 836
Mean (Standard Error)
Unit of Measure: Units on a Scale
Total Score -9.84  (0.25) -7.97  (0.25)
Anxiety Scale -3.06  (0.09) -2.41  (0.09)
Depression Scale -2.35  (0.08) -1.77  (0.08)
Sexual Dysfunction Scale -0.46  (0.03) -0.41  (0.03)
Psychological Scale -5.39  (0.15) -4.15  (0.15)
Somatic Scale -1.49  (0.08) -1.31  (0.08)
Vasomotor Scale -2.55  (0.06) -2.14  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -1.87
Confidence Interval (2-Sided) 95%
-2.57 to -1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-0.90 to -0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.80 to -0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.282
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.13 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-1.66 to -0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.41 to 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.56 to -0.26
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 673 718
Mean (Standard Error)
Unit of Measure: Units on a Scale
Total Score -10.60  (0.26) -8.89  (0.25)
Anxiety Scale -3.25  (0.09) -2.69  (0.09)
Depression Scale -2.66  (0.08) -2.04  (0.08)
Sexual Dysfunction Scale -0.51  (0.03) -0.43  (0.03)
Psychological Scale -5.88  (0.16) -4.70  (0.15)
Somatic Scale -1.63  (0.09) -1.61  (0.08)
Vasomotor Scale -2.64  (0.06) -2.19  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -1.71
Confidence Interval (2-Sided) 95%
-2.42 to -1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.81 to -0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-0.83 to -0.40
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.17 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-1.61 to -0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.865
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.25 to 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.61 to -0.29
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 961 982
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 8.8 5.0
2= Minimal 27.8 18.5
3= Mild 28.9 26.5
4= Moderate 24.9 33.8
5= Severe 9.6 16.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 963 986
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 8.5 5.7
2= Minimal 32.2 25.5
3= Mild 27.3 23.1
4= Moderate 22.9 31.1
5= Severe 9.0 14.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 963 986
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 10.1 7.1
2= Minimal 32.2 27.8
3= Mild 25.9 21.0
4= Moderate 21.6 29.7
5= Severe 10.3 14.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 8.1 1.7
2= Minimal 20.3 10.9
3= Mild 29.1 16.6
4= Moderate 24.4 42.9
5= Severe 18.0 28.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
19.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 12.2 2.9
2= Minimal 29.7 18.3
3= Mild 27.3 17.7
4= Moderate 16.9 34.3
5= Severe 14.0 26.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
20.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= None 9.3 4.0
2= Minimal 28.5 17.1
3= Mild 26.7 12.6
4= Moderate 18.0 39.4
5= Severe 17.4 26.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 962 983
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 25.8 13.1
2= Much Improved 32.3 25.5
3= Minimally Improved 23.3 25.1
4= No Change 11.5 29.3
5= Minimally Worse 4.1 4.5
6= Much Worse 2.2 1.7
7= Very Much Worse 0.8 0.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
22.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 963 986
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 28.9 17.1
2= Much Improved 32.3 27.7
3= Minimally Improved 20.5 20.6
4= No Change 11.6 26.2
5= Minimally Worse 3.5 5.2
6= Much Worse 2.1 2.6
7= Very Much Worse 1.1 0.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
23.Secondary Outcome
Title Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 963 986
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 31.0 19.9
2= Much Improved 29.2 24.5
3= Minimally Improved 21.1 21.5
4= No Change 12.7 26.8
5= Minimally Worse 2.4 4.4
6= Much Worse 2.7 2.0
7= Very Much Worse 0.9 0.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
24.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 26.7 7.4
2= Much Improved 35.5 22.3
3= Minimally Improved 17.4 29.7
4= No Change 12.8 34.3
5= Minimally Worse 2.9 4.6
6= Much Worse 3.5 1.7
7= Very Much Worse 1.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
25.Secondary Outcome
Title Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 34.9 14.9
2= Much Improved 32.6 25.7
3= Minimally Improved 15.7 23.4
4= No Change 11.0 29.7
5= Minimally Worse 2.3 4.0
6= Much Worse 2.9 2.3
7= Very Much Worse 0.6 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
26.Secondary Outcome
Title Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 172 175
Measure Type: Number
Unit of Measure: Percentage of Participants
1= Very Much Improved 37.2 13.7
2= Much Improved 24.4 18.3
3= Minimally Improved 21.5 25.1
4= No Change 10.5 36.0
5= Minimally Worse 1.2 5.1
6= Much Worse 4.1 1.7
7= Very Much Worse 1.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments A Cochran-Mantel-Haenszel row mean score test was used to compare the treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
27.Other Pre-specified Outcome
Title Number of Participants With Adjudicated Cerebrovascular Events - Any Stroke
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study medication.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 1066 1052
Measure Type: Number
Unit of Measure: Participants
Any Stroke (Definite or Probable) 1 0
Definite Stroke 0 0
Probable Stroke 1 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Wald Formula
Estimated Value 1.11
Confidence Interval (2-Sided) 90%
-0.68 to 2.9
Estimation Comments The 90% CI for excess risk is obtained using the Wald Formula.
28.Other Pre-specified Outcome
Title Number of Participants With Adjudicated Cerebrovascular Events - Probable TIA
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study medication.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 1066 1052
Measure Type: Number
Unit of Measure: Participants
1 0
29.Other Pre-specified Outcome
Title Number of Participants With Ischemic Heart Disease
Hide Description Potential ischaemic cardiac events were identified using the Standardized MedDRA Query (SMQ) "Ischemic Heart Disease".
Time Frame Baseline up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study medication.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 1066 1052
Measure Type: Number
Unit of Measure: Participants
4 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Wald Formula
Estimated Value 2.31
Confidence Interval (2-Sided) 90%
-2.08 to 6.71
Estimation Comments The 90% CI for excess risk is obtained using the Wald Formula.
30.Other Pre-specified Outcome
Title Number of Participants With Hepatic Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study medication.
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description:
Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal.
Matching placebo tablets daily until Day 365 or early withdrawal.
Overall Number of Participants Analyzed 1066 1052
Measure Type: Number
Unit of Measure: Participants
2 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 100 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Wald Formula
Estimated Value 0.08
Confidence Interval (2-Sided) 90%
-3.51 to 3.67
Estimation Comments The 90% CI for excess risk is obtained using the Wald Formula.
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title DVS SR 100 mg Placebo
Hide Arm/Group Description Desvenlafaxine Succinate Sustained Release (DVS SR) 100 milligram (mg) tablets daily until Day 365 or early withdrawal. Matching placebo tablets daily until Day 365 or early withdrawal.
All-Cause Mortality
DVS SR 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DVS SR 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   43/1066 (4.03%)   36/1052 (3.42%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Angina pectoris * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Atrial fibrillation * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Coronary artery occlusion * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Palpitations * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Congenital, familial and genetic disorders     
Cerebrovascular arteriovenous malformation * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Ear and labyrinth disorders     
Vertigo * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Eye disorders     
Glaucoma * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Narrow anterior chamber angle * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Retinal haemorrhage * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Colitis ischaemic * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Diverticular perforation * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Gastrooesophageal reflux disease * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Ileus * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Ileus paralytic * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Stomatitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Swollen tongue * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/1066 (0.09%)  0/1052 (0.00%) 
General disorders     
Chest pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Drug therapeutic incompatibility * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Fatigue * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Non-cardiac chest pain * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Hepatobiliary disorders     
Biliary dyskinesia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Cholecystitis * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Infections and infestations     
Cellulitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Diverticulitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Enterocolitis viral * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Escherichia sepsis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Herpes zoster * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Laryngitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Pneumonia * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Pyelonephritis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Subcutaneous abscess * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Injury, poisoning and procedural complications     
Drug toxicity * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Hand fracture * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Injury * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Intentional overdose * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Limb injury * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Patella fracture * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Radius fracture * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Traumatic intracranial haemorrhage * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Ulna fracture * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Investigations     
Blood creatine phosphokinase MB increased * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Blood pressure increased * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Cardiac stress test abnormal * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Electrocardiogram T wave abnormal * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Electrocardiogram T wave inversion * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Electrocardiogram abnormal * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Metabolism and nutrition disorders     
Hypokalaemia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Bunion * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Flank pain * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Foot deformity * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Intervertebral disc protrusion * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Knee deformity * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Musculoskeletal chest pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Osteoarthritis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pain in extremity * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Breast cancer * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Carcinoid tumour pulmonary * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Dermatofibrosarcoma * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Lung adenocarcinoma * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Malignant melanoma in situ * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Multiple myeloma * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Non-small cell lung cancer stage III * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Ovarian cancer recurrent * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pancreatic carcinoma metastatic * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Squamous cell carcinoma of skin * 1  4/1066 (0.38%)  1/1052 (0.10%) 
Thyroid cancer * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Transitional cell carcinoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Uterine leiomyoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Nervous system disorders     
Ageusia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Carotid artery occlusion * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Cerebral haematoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Cervical myelopathy * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Convulsion * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Dysarthria * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Hypoaesthesia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Migraine * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Paraesthesia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Presyncope * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Transient ischaemic attack * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Psychiatric disorders     
Major depression * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Mental status changes * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Renal failure acute * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Reproductive system and breast disorders     
Endometrial hyperplasia * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Asthma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Chronic obstructive pulmonary disease * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Non-cardiogenic pulmonary oedema * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pulmonary embolism * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pruritus * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Rash * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vascular disorders     
Hypertension * 1  1/1066 (0.09%)  0/1052 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DVS SR 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   941/1066 (88.27%)   872/1052 (82.89%) 
Blood and lymphatic system disorders     
Anaemia * 1  7/1066 (0.66%)  5/1052 (0.48%) 
Leukopenia * 1  3/1066 (0.28%)  4/1052 (0.38%) 
Lymph node pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Lymphadenitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Lymphadenopathy * 1  4/1066 (0.38%)  7/1052 (0.67%) 
Neutropenia * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Pancytopenia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pernicious anaemia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Splenic granuloma * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Thrombocytopenia * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Cardiac disorders     
Aortic valve incompetence * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Arrhythmia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Atrial fibrillation * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Atrioventricular block first degree * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Bundle branch block left * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Cardiac flutter * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Conduction disorder * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Palpitations * 1  35/1066 (3.28%)  33/1052 (3.14%) 
Pulmonary valve incompetence * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Right atrial dilatation * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Sinus tachycardia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Supraventricular extrasystoles * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Tachycardia * 1  7/1066 (0.66%)  7/1052 (0.67%) 
Ventricular extrasystoles * 1  4/1066 (0.38%)  0/1052 (0.00%) 
Congenital, familial and genetic disorders     
Keratosis follicular * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Mixed hyperlipidaemia * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Ear and labyrinth disorders     
Cerumen impaction * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Conductive deafness * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Deafness * 1  3/1066 (0.28%)  1/1052 (0.10%) 
Ear canal stenosis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Ear congestion * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Ear discomfort * 1  2/1066 (0.19%)  4/1052 (0.38%) 
Ear disorder * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Ear haemorrhage * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Ear pain * 1  16/1066 (1.50%)  8/1052 (0.76%) 
Ear pruritus * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Eustachian tube dysfunction * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Meniere's disease * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Middle ear effusion * 1  3/1066 (0.28%)  2/1052 (0.19%) 
Motion sickness * 1  4/1066 (0.38%)  5/1052 (0.48%) 
Otosclerosis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Tinnitus * 1  36/1066 (3.38%)  4/1052 (0.38%) 
Tympanic membrane disorder * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vertigo * 1  43/1066 (4.03%)  8/1052 (0.76%) 
Vertigo positional * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Endocrine disorders     
Goitre * 1  3/1066 (0.28%)  5/1052 (0.48%) 
Hyperthyroidism * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Hypothyroidism * 1  3/1066 (0.28%)  11/1052 (1.05%) 
Eye disorders     
Altered visual depth perception * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Angle closure glaucoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Asthenopia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Astigmatism * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Blepharitis * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Blepharospasm * 1  3/1066 (0.28%)  4/1052 (0.38%) 
Cataract * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Conjunctival haemorrhage * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Conjunctivitis * 1  6/1066 (0.56%)  2/1052 (0.19%) 
Dry eye * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Episcleritis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Eye irritation * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Eye pain * 1  6/1066 (0.56%)  1/1052 (0.10%) 
Eye pruritus * 1  2/1066 (0.19%)  8/1052 (0.76%) 
Eye swelling * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Eyelid cyst * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Eyelid oedema * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Eyelid ptosis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Glaucoma * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Iritis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Keratoconjunctivitis sicca * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Lacrimation increased * 1  3/1066 (0.28%)  3/1052 (0.29%) 
Macular degeneration * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Macular oedema * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Mydriasis * 1  6/1066 (0.56%)  1/1052 (0.10%) 
Myopia * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Narrow anterior chamber angle * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Night blindness * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Ocular hyperaemia * 1  4/1066 (0.38%)  0/1052 (0.00%) 
Photophobia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Photopsia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pinguecula * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Presbyopia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Pupil fixed * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Retinal aneurysm * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Retinopathy hypertensive * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Scleral hyperaemia * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Ulcerative keratitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Vision blurred * 1  25/1066 (2.35%)  10/1052 (0.95%) 
Visual acuity reduced * 1  3/1066 (0.28%)  1/1052 (0.10%) 
Visual impairment * 1  4/1066 (0.38%)  0/1052 (0.00%) 
Vitreous degeneration * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vitreous detachment * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Vitreous floaters * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  22/1066 (2.06%)  20/1052 (1.90%) 
Abdominal distension * 1  16/1066 (1.50%)  8/1052 (0.76%) 
Abdominal mass * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Abdominal pain * 1  23/1066 (2.16%)  24/1052 (2.28%) 
Abdominal pain lower * 1  2/1066 (0.19%)  7/1052 (0.67%) 
Abdominal pain upper * 1  39/1066 (3.66%)  41/1052 (3.90%) 
Abdominal tenderness * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Abnormal faeces * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Anal fissure * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Aphthous stomatitis * 1  4/1066 (0.38%)  0/1052 (0.00%) 
Bowel movement irregularity * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Change of bowel habit * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Cheilitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Coeliac disease * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Colitis * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Colitis microscopic * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Colonic polyp * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Constipation * 1  118/1066 (11.07%)  40/1052 (3.80%) 
Crohn's disease * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Dental caries * 1  8/1066 (0.75%)  4/1052 (0.38%) 
Diarrhoea * 1  79/1066 (7.41%)  56/1052 (5.32%) 
Diarrhoea haemorrhagic * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Diverticulum * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Dry mouth * 1  88/1066 (8.26%)  15/1052 (1.43%) 
Duodenal ulcer * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Dyspepsia * 1  63/1066 (5.91%)  50/1052 (4.75%) 
Dysphagia * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Enterocolitis haemorrhagic * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Eructation * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Faeces discoloured * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Faeces hard * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Flatulence * 1  20/1066 (1.88%)  5/1052 (0.48%) 
Food poisoning * 1  3/1066 (0.28%)  2/1052 (0.19%) 
Frequent bowel movements * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Gastritis * 1  4/1066 (0.38%)  2/1052 (0.19%) 
Gastrointestinal haemorrhage * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Gastrointestinal pain * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Gastrooesophageal reflux disease * 1  20/1066 (1.88%)  18/1052 (1.71%) 
Gingival erosion * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Gingival pain * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Gingival swelling * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Gingival ulceration * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Glossodynia * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Haematochezia * 1  3/1066 (0.28%)  1/1052 (0.10%) 
Haemorrhoidal haemorrhage * 1  0/1066 (0.00%)  3/1052 (0.29%) 
Haemorrhoids * 1  6/1066 (0.56%)  8/1052 (0.76%) 
Hiatus hernia * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Hyperchlorhydria * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Hypoaesthesia oral * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Infrequent bowel movements * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Irritable bowel syndrome * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Lip blister * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Lip swelling * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Lower gastrointestinal haemorrhage * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Mouth ulceration * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Nausea * 1  279/1066 (26.17%)  89/1052 (8.46%) 
Odynophagia * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Oesophageal pain * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Oesophageal ulcer * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Oesophagitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Oral disorder * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Oral pain * 1  7/1066 (0.66%)  0/1052 (0.00%) 
Oral pruritus * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Paraesthesia oral * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Peptic ulcer * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Periodontal disease * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Periodontitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Polyp colorectal * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Proctalgia * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Proctitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Rectal haemorrhage * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Retching * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Salivary gland enlargement * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Salivary gland pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Salivary hypersecretion * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Sensitivity of teeth * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Stomatitis * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Swollen tongue * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Tongue dry * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Tooth discolouration * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Tooth impacted * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Tooth loss * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Toothache * 1  37/1066 (3.47%)  30/1052 (2.85%) 
Vomiting * 1  50/1066 (4.69%)  26/1052 (2.47%) 
General disorders     
Asthenia * 1  27/1066 (2.53%)  11/1052 (1.05%) 
Axillary pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Chest discomfort * 1  9/1066 (0.84%)  11/1052 (1.05%) 
Chest pain * 1  4/1066 (0.38%)  6/1052 (0.57%) 
Chills * 1  28/1066 (2.63%)  8/1052 (0.76%) 
Cyst * 1  3/1066 (0.28%)  2/1052 (0.19%) 
Device breakage * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Device malfunction * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Drug intolerance * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Drug withdrawal syndrome * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Energy increased * 1  3/1066 (0.28%)  1/1052 (0.10%) 
Facial pain * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Fatigue * 1  109/1066 (10.23%)  35/1052 (3.33%) 
Feeling abnormal * 1  6/1066 (0.56%)  3/1052 (0.29%) 
Feeling cold * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Feeling drunk * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Feeling hot * 1  1/1066 (0.09%)  3/1052 (0.29%) 
Feeling jittery * 1  18/1066 (1.69%)  1/1052 (0.10%) 
Feeling of body temperature change * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Generalised oedema * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Hangover * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Hunger * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Impaired healing * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Implant site reaction * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Inflammation * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Influenza like illness * 1  13/1066 (1.22%)  14/1052 (1.33%) 
Injection site haematoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Injection site pain * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Irritability * 1  32/1066 (3.00%)  19/1052 (1.81%) 
Local swelling * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Malaise * 1  8/1066 (0.75%)  4/1052 (0.38%) 
Mass * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Medical device pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Nodule * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Non-cardiac chest pain * 1  8/1066 (0.75%)  9/1052 (0.86%) 
Oedema * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Oedema peripheral * 1  12/1066 (1.13%)  14/1052 (1.33%) 
Pain * 1  41/1066 (3.85%)  40/1052 (3.80%) 
Pyrexia * 1  21/1066 (1.97%)  21/1052 (2.00%) 
Rebound effect * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Sluggishness * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Temperature intolerance * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Therapeutic response unexpected * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Thirst * 1  3/1066 (0.28%)  5/1052 (0.48%) 
Ulcer * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Unevaluable event * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vaccination site induration * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Vessel puncture site haematoma * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vessel puncture site pain * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Vestibulitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Hepatobiliary disorders     
Cholecystitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Gallbladder pain * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Hepatic cirrhosis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Hepatic cyst * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Immune system disorders     
Allergy to animal * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Allergy to arthropod sting * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Allergy to chemicals * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Allergy to plants * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Allergy to vaccine * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Contrast media allergy * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Drug hypersensitivity * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Food allergy * 1  0/1066 (0.00%)  2/1052 (0.19%) 
House dust allergy * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Hypersensitivity * 1  7/1066 (0.66%)  5/1052 (0.48%) 
Sarcoidosis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Seasonal allergy * 1  17/1066 (1.59%)  22/1052 (2.09%) 
Infections and infestations     
Abdominal abscess * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Abscess * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Abscess intestinal * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Abscess limb * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Acute sinusitis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Anal abscess * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Anal fungal infection * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Asymptomatic bacteriuria * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Bacterial infection * 1  3/1066 (0.28%)  0/1052 (0.00%) 
Breast abscess * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Breast cellulitis * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Breast infection * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Bronchitis * 1  34/1066 (3.19%)  35/1052 (3.33%) 
Bronchitis viral * 1  2/1066 (0.19%)  0/1052 (0.00%) 
Bronchopneumonia * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Cellulitis * 1  2/1066 (0.19%)  2/1052 (0.19%) 
Cervicitis * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Conjunctivitis bacterial * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Conjunctivitis infective * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Cystitis * 1  14/1066 (1.31%)  15/1052 (1.43%) 
Diverticulitis * 1  2/1066 (0.19%)  6/1052 (0.57%) 
Ear infection * 1  12/1066 (1.13%)  17/1052 (1.62%) 
Ear infection viral * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Eye abscess * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Eye infection * 1  9/1066 (0.84%)  4/1052 (0.38%) 
Eye infection viral * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Folliculitis * 1  5/1066 (0.47%)  1/1052 (0.10%) 
Fungal infection * 1  2/1066 (0.19%)  7/1052 (0.67%) 
Fungal skin infection * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Furuncle * 1  2/1066 (0.19%)  3/1052 (0.29%) 
Gastroenteritis * 1  9/1066 (0.84%)  6/1052 (0.57%) 
Gastroenteritis viral * 1  24/1066 (2.25%)  15/1052 (1.43%) 
Gastrointestinal infection * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Gastrointestinal viral infection * 1  6/1066 (0.56%)  1/1052 (0.10%) 
Genital herpes * 1  1/1066 (0.09%)  2/1052 (0.19%) 
Gingival infection * 1  4/1066 (0.38%)  2/1052 (0.19%) 
H1N1 influenza * 1  0/1066 (0.00%)  2/1052 (0.19%) 
Helicobacter infection * 1  3/1066 (0.28%)  3/1052 (0.29%) 
Herpes ophthalmic * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Herpes simplex * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Herpes zoster * 1  5/1066 (0.47%)  9/1052 (0.86%) 
Hordeolum * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Incision site infection * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Infected bites * 1  2/1066 (0.19%)  1/1052 (0.10%) 
Infected cyst * 1  1/1066 (0.09%)  1/1052 (0.10%) 
Infected sebaceous cyst * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Infectious mononucleosis * 1  0/1066 (0.00%)  1/1052 (0.10%) 
Influenza * 1  60/1066 (5.63%)  61/1052 (5.80%) 
Keratitis herpetic * 1  1/1066 (0.09%)  0/1052 (0.00%) 
Kidney infection * 1  3/1066 (0.28%)  1/1052 (0.10%) 
Labyrinthitis * 1  3/1066 (0.28%)  2/1052 (0.19%) 
Laryngitis * 1  3/1066 (0.28%)  5/1052 (0.48%)