Study Evaluating Desvenlafaxine Succinate Sustained Release In Adults With Major Depressive Disorder
Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00863798
Collaborator
Pfizer (Industry)
682
24
3
11
28.4
2.6
Study Details
Study Description
Brief Summary
The primary purpose of this study is to compare the antidepressant efficacy and safety of two doses of desvenlafaxine succinate sustained release (10 and 50 mg/day) in adults with Major Depressive Disorder. The study will also assess changes in sexual function and general and functional quality of life outcomes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
682 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Evaluate The Efficacy And Safety Of 2 Fixed Doses (10 And 50 mg/Day) Of DVS SR Tablets In Adult Outpatients With Major Depressive Disorder
Study Start Date
:
Apr 1, 2009
Actual Primary Completion Date
:
Mar 1, 2010
Actual Study Completion Date
:
Mar 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Desvenlafaxine succinate sustained release 10 mg
|
Drug: Desvenlafaxine Succinate Sustained-Release 10mg
10 mg tablet, once daily dosing for 8 weeks
|
| Experimental: Desvenlafaxine succinate sustained release 50 mg
|
Drug: Desvenlafaxine Succinate Sustained-Release 50 mg
50 mg tablet, once daily dosing for 8 weeks
|
| Placebo Comparator: Placebo
|
Drug: placebo
Matching placebo tablets (10 or 50mg). Daily dosing for 10 +/- 4 days during a placebo lead-in period, and then 8 weeks during the double-blind period.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in HAM-D17 Total Score at Final On-therapy (FOT) Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET)]
HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
Secondary Outcome Measures
- Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
- Change From Baseline in Mean CGI-S Score at FOT Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET )]
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
- Change From Baseline in MADRS Total Score at FOT Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET)]
MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
- Change From Baseline in HAM-D6 Total Score at FOT Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET )]
HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. 0=none/absent and 22=most severe.The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 and all others are scored 0-4.
- Number of Participants With a Response on the HAM-D17 at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
A HAM-D17 responder was defined as a participant with a 50% or greater decrease from baseline in HAM-D17 score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
- Number of Participants in Remission Based on the HAM-D17 at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
Remission was defined as a HAM-D17 score of less than or equal to 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
- Number of Participants With a Response on the MADRS Score at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
A MADRS responder was defined as a participant with a 50% or greater decrease from baseline in MADRS score. It measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
- Number of Participants With a Response on the CGI-I Score at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
CGI-I responder was defined as a participant with a score of 1 (very much improved) or 2 (much improved) on the CGI-I. CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Other Outcome Measures
- Population Pharmacokinetics for Desvenlafaxine Plasma Concentrations [Week 2, 4 and 8 (or ET)]
Relationship of demographic variables (age, gender, food, race, creatinine, aspartate aminotransaminase, alanine transaminase, bilirubin and concomitant medications) were examined by fitting measured DVS plasma concentrations to a 1 compartment model with first order absorption. Demographic variables were examined for clearance (CL/F), volume of distribution (V/F), Steady Area under Curve (AUC) using nonlinear mixed effects modeling. Final parameter estimates for demographic factors effecting CL/F, V/F and AUC were determined.
- Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET)]
SDS: a self-administered tools that measures functional impairment in 3 domains: Work/School, Social Life, and Family Life/Home Responsibilities. The participant rates the extent to which each of these domains is impaired by his/her symptoms using a 10 point visual analog scale: (0=not at all impaired, 10=extremely impaired) for a total maximum score of 30.
- Change From Baseline in WHO-5 Total Score at FOT Evaluation (Week 8 or ET) [Baseline and Week 8 (or ET)]
WHO-5 evaluates positive psychological well-being. WHO-5 consists of 5 questions and each is rated on a 6-point scale. The total score ranges from 0 to 25 (0= worst possible quality of life; 25=best possible quality of life).
- Percentage of Participants With Sexual Dysfunction at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
ASEX scale includes 5 questions that evaluate sexual function exclusively during the week prior to completion in the following areas: libido, excitability and ability to reach orgasm. Sexual dysfunction=an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. Participants who have had no sexual activity during the prior week were instructed to not complete questions 3 through 5.
- Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) [Week 8 (or ET)]
C-SSRS mapped into C-CASA(1-7) to assess whether participant:completed suicide(1),suicide attempt(2)(response of "Yes" on "Actual Attempt"),preparatory acts toward imminent suicidal behavior (3)("Yes" on "Preparatory Acts or Behavior"),suicidal ideation (4)("Yes" on "Wish to be dead","Non-Specific Active Suicidal Thoughts","Active Suicidal Ideation with methods without Intent to Act or Some Intent to Act,without Specific Plan or with Specific Plan and Intent),any suicidal behavior or ideation,self-injurious behaviour(7)("Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior").
- Discontinuation-Emergent Signs and Symptoms (DESS) [Week 8 to 10 (or ET)]
DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of new symptoms and old (but worse) symptoms that appeared during tapering of the test article. A higher score indicates more symptoms.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adult, outpatient with primary diagnosis of Major Depressive Disorder (depressive symptoms for at least 30 days prior to screening).
-
Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) total score of >= 20.
-
Clinical Global Impressions Scale-Severity (CGI-S) score of >= 4.
Exclusion Criteria:
-
Clinical instability (25% or greater increase/decrease in HAM-D 17 total score from screening to baseline).
-
Significant risk of suicide as assessed by clinician judgment, HAM-D 17 and Columbia Suicide-Severity Rating Scale scores Other eligibility criteria also apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35216 |
| 2 | Pfizer Investigational Site | Encino | California | United States | 91316 |
| 3 | Pfizer Investigational Site | Newport Beach | California | United States | 92660 |
| 4 | Pfizer Investigational Site | Redlands | California | United States | 92374 |
| 5 | Pfizer Investigational Site | Upland | California | United States | 91786 |
| 6 | Pfizer Investigational Site | Aurora | Colorado | United States | 80045 |
| 7 | Pfizer Investigational Site | Denver | Colorado | United States | 80204 |
| 8 | Pfizer Investigational Site | Cromwell | Connecticut | United States | 06416 |
| 9 | Pfizer Investigational Site | Maitland | Florida | United States | 32751 |
| 10 | Pfizer Investigational Site | North Miami | Florida | United States | 33161 |
| 11 | Pfizer Investigational Site | South Miami | Florida | United States | 33143 |
| 12 | Pfizer Investigational Site | Indianapolis | Indiana | United States | 46260 |
| 13 | Pfizer Investigational Site | St. Louis | Missouri | United States | 63139 |
| 14 | Pfizer Investigational Site | New York | New York | United States | 10128 |
| 15 | Pfizer Investigational Site | Staten Island | New York | United States | 10312 |
| 16 | Pfizer Investigational Site | Toledo | Ohio | United States | 43623 |
| 17 | Pfizer Investigational Site | Eugene | Oregon | United States | 97401 |
| 18 | Pfizer Investigational Site | Portland | Oregon | United States | 97210 |
| 19 | Pfizer Investigational Site | Salem | Oregon | United States | 97301 |
| 20 | Pfizer Investigational Site | Media | Pennsylvania | United States | 19063 |
| 21 | Pfizer Investigational Site | Herndon | Virginia | United States | 20170 |
| 22 | Pfizer Investigational Site | Midlothian | Virginia | United States | 23112 |
| 23 | Pfizer Investigational Site | Middleton | Wisconsin | United States | 53562 |
| 24 | Pfizer Investigational Site | Waukesha | Wisconsin | United States | 53188 |
Sponsors and Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00863798
Other Study ID Numbers:
- 3151A1-3362
- B2061005
- 3151A1-3362-US
First Posted:
Mar 18, 2009
Last Update Posted:
May 6, 2011
Last Verified:
Apr 1, 2011
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 898 potential participants were screened for this study. 804 participants were enrolled and received single-blind placebo during the screening period prior to randomization. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Period Title: Overall Study | |||
| STARTED | 227 | 228 | 227 |
| Treated | 223 | 226 | 224 |
| COMPLETED | 195 | 198 | 202 |
| NOT COMPLETED | 32 | 30 | 25 |
Baseline Characteristics
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. | Total of all reporting groups |
| Overall Participants | 223 | 226 | 224 | 673 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
41.75
(12.85)
|
41.01
(13.75)
|
42.47
(13.47)
|
41.74
(13.36)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
139
62.3%
|
135
59.7%
|
135
60.3%
|
409
60.8%
|
| Male |
84
37.7%
|
91
40.3%
|
89
39.7%
|
264
39.2%
|
| Hamilton Psychiatric Scale for Depression-17 item HAM-D17) total score (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
23.23
(2.63)
|
22.83
(2.26)
|
23.12
(2.62)
|
23.06
(2.51)
|
| Clinical Global Impressions Scale-Severity of Illness (CGI-S) Score (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
4.14
(0.35)
|
4.14
(0.34)
|
4.16
(0.39)
|
4.14
(0.36)
|
| Montgomery-Asberg Depression Rating Scale (MADRS) total score (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
28.33
(4.71)
|
27.59
(4.49)
|
28.44
(4.83)
|
28.12
(4.69)
|
| HAM-D6 total score (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
12.72
(1.51)
|
12.77
(1.41)
|
12.63
(1.49)
|
12.71
(1.47)
|
| Sheehan Disability Scale (SDS) Total Score (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
16.88
(8.25)
|
16.42
(8.37)
|
17.06
(7.73)
|
16.78
(8.12)
|
| World Health Organization 5-Item Well-Being Index (WHO-5) (Units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units on a scale] |
7.39
(4.80)
|
7.47
(4.86)
|
7.06
(4.26)
|
7.31
(4.65)
|
| Participants with Sexual dysfunction (Percentage of Participants) [Number] | ||||
| Number [Percentage of Participants] |
58.8
26.4%
|
61.3
27.1%
|
65.8
29.4%
|
185.9
27.6%
|
| Participants with Columbia Suicide-Severity Rating Scale (C-SSRS) total score (Number) [Number] | ||||
| Completed Suicide |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Suicide Attempt |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Preparatory acts toward imminent suicidal behavior |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Suicidal ideation |
37
16.6%
|
31
13.7%
|
29
12.9%
|
97
14.4%
|
Outcome Measures
| Title | Change From Baseline in HAM-D17 Total Score at Final On-therapy (FOT) Evaluation (Week 8 or ET) |
|---|---|
| Description | HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50. |
| Time Frame | Baseline and Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) Population:all randomly assigned participants with baseline primary efficacy evaluation, had taken at least 1 dose of double-blind drug and 1 primary efficacy evaluation after first dose of double-blind drug. If participant had missing value at any visit, last observation carried forward (LOCF) method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Mean (Standard Error) [Units on a scale] |
-8.42
(0.45)
|
-9.28
(0.45)
|
-8.92
(0.45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | An analysis of covariance (ANCOVA) model with treatment and as a factor and the baseline HAM-D17 total score as a covariate was used to compare DVS SR 10 mg to placebo. The comparison was performed at the 0.05 level overall. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.175 |
| Comments | A Hochberg step-up procedure was used to control for the multiplicity associated with multiple active dose arms. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.86 | |
| Confidence Interval |
(2-Sided) 95% -0.38 to 2.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | An analysis of covariance (ANCOVA) model with treatment and as a factor and the baseline HAM-D17 total score as a covariate was used to compare DVS SR 10 mg to placebo. The comparison was performed at the 0.05 level overall. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.421 |
| Comments | A Hochberg step-up procedure was used to control for the multiplicity associated with multiple active dose arms. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.51 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to 1.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| 1=Very much improved |
49
22%
|
50
22.1%
|
55
24.6%
|
| 2=Much improved |
54
24.2%
|
75
33.2%
|
53
23.7%
|
| 3=Minimally improved |
51
22.9%
|
51
22.6%
|
64
28.6%
|
| 4=No change |
61
27.4%
|
46
20.4%
|
49
21.9%
|
| 5=Minimally worse |
5
2.2%
|
4
1.8%
|
3
1.3%
|
| 6=Much worse |
3
1.3%
|
0
0%
|
0
0%
|
| 7=Very much worse |
0
0%
|
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Each DVS SR dose was separately compared to placebo. To control the study-wise type I error rate across the primary and the key secondary endpoints, as well as across the 2 active dose arms, testing of the key secondary hypothesis occurred only when both active doses were superior to placebo on the primary endpoint. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.076 |
| Comments | In this case, multiplicity arising from testing key secondary hypotheses in both doses was controlled by a Hochberg step-up procedure. p-Value obtained for the alternative hypothesis of 'Row mean scores differences'. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Each DVS SR dose was separately compared to placebo. To control the study-wise type I error rate across the primary and the key secondary endpoints, as well as across the 2 active dose arms, testing of the key secondary hypothesis occurred only when both active doses were superior to placebo on the primary endpoint. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.204 |
| Comments | In this case, multiplicity arising from testing key secondary hypotheses in both doses was controlled by a Hochberg step-up procedure. p-Value obtained for the alternative hypothesis of 'Row mean scores differences'. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change From Baseline in Mean CGI-S Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. |
| Time Frame | Baseline and Week 8 (or ET ) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Mean (Standard Error) [Units on a scale] |
-1.08
(0.07)
|
-1.23
(0.07)
|
-1.11
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.130 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.04 to 0.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.757 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.16 to 0.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MADRS Total Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Time Frame | Baseline and Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 222 | 224 | 222 |
| Mean (Standard Error) [Units on a scale] |
-9.87
(0.63)
|
-11.28
(0.63)
|
-10.76
(0.63)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.114 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 1.41 | |
| Confidence Interval |
(2-Sided) 95% -0.34 to 3.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.316 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% -0.85 to 2.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in HAM-D6 Total Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. 0=none/absent and 22=most severe.The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 and all others are scored 0-4. |
| Time Frame | Baseline and Week 8 (or ET ) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Mean (Standard Error) [Units on a scale] |
-4.75
(0.27)
|
-5.49
(0.27)
|
-5.19
(0.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.054 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 1.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.253 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 1.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With a Response on the HAM-D17 at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | A HAM-D17 responder was defined as a participant with a 50% or greater decrease from baseline in HAM-D17 score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50. |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Number [Participants] |
85
38.1%
|
100
44.2%
|
91
40.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment as a factor and baseline HAM-D17 score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2415 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.254 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 1.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment as a factor and baseline HAM-D17 score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6169 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.102 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants in Remission Based on the HAM-D17 at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | Remission was defined as a HAM-D17 score of less than or equal to 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50. |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Number [Participants] |
42
18.8%
|
52
23%
|
39
17.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment as a factor and baseline HAM-D17 score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3667 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.236 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment as a factor and baseline HAM-D17 score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6509 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.894 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 1.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With a Response on the MADRS Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | A MADRS responder was defined as a participant with a 50% or greater decrease from baseline in MADRS score. It measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 222 | 224 | 222 |
| Number [Participants] |
84
37.7%
|
95
42%
|
90
40.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis would be conducted with a logistic regression model with treatment as a factor and baseline MADRS score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3893 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.182 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 1.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis would be conducted with a logistic regression model with treatment as a factor and baseline MADRS score as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5510 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.123 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 1.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With a Response on the CGI-I Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | CGI-I responder was defined as a participant with a score of 1 (very much improved) or 2 (much improved) on the CGI-I. CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Number [Participants] |
103
46.2%
|
125
55.3%
|
108
48.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis would be conducted with a logistic regression model with treatment as a factor. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0536 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.442 | |
| Confidence Interval |
(2-Sided) 95% 0.99 to 2.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis would be conducted with a logistic regression model with treatment as a factor. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6679 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.085 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Population Pharmacokinetics for Desvenlafaxine Plasma Concentrations |
|---|---|
| Description | Relationship of demographic variables (age, gender, food, race, creatinine, aspartate aminotransaminase, alanine transaminase, bilirubin and concomitant medications) were examined by fitting measured DVS plasma concentrations to a 1 compartment model with first order absorption. Demographic variables were examined for clearance (CL/F), volume of distribution (V/F), Steady Area under Curve (AUC) using nonlinear mixed effects modeling. Final parameter estimates for demographic factors effecting CL/F, V/F and AUC were determined. |
| Time Frame | Week 2, 4 and 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population; data was insufficient examine the effect of demographic variables on the PK of desvenlafaxine. Parameter values were calculated for variables altering CL/F, AUC and V/F. Population parameters from nonlinear mixed effects modeling were not summarized as descriptive statistics. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | SDS: a self-administered tools that measures functional impairment in 3 domains: Work/School, Social Life, and Family Life/Home Responsibilities. The participant rates the extent to which each of these domains is impaired by his/her symptoms using a 10 point visual analog scale: (0=not at all impaired, 10=extremely impaired) for a total maximum score of 30. |
| Time Frame | Baseline and Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation,had taken at least 1 dose of double-blind study drug,had at least 1 primary efficacy evaluation after first dose of double-blind drug.'n' is participants who received drug and were evaluated for measure at timepoint for each group respectively. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Total Score (n=220,223,219) |
-2.63
(0.48)
|
-4.09
(0.48)
|
-3.78
(0.49)
|
| Work/Studies Component(n=220,223,219) |
-0.61
(0.17)
|
-1.10
(0.17)
|
-1.14
(0.17)
|
| Social Life and Leisure Activities(n=222,224,221) |
-1.08
(0.18)
|
-1.58
(0.17)
|
-1.36
(0.18)
|
| Family Life/Home Responsibilities (n=222,224,221) |
-0.98
(0.17)
|
-1.43
(0.17)
|
-1.20
(0.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "total score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.46 | |
| Confidence Interval |
(2-Sided) 95% 0.12 to 2.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "total score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.096 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.15 | |
| Confidence Interval |
(2-Sided) 95% -0.20 to 2.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "work/studies component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.043 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "work/studies component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.06 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "social life and leisure activities component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.045 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% 0.01 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "social life and leisure activities component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.277 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.27 | |
| Confidence Interval |
(2-Sided) 95% -0.22 to 0.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "family life/home responsibilities component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.056 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 0.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate for "family life/home responsibilities component score". | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.355 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.22 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to 0.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in WHO-5 Total Score at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | WHO-5 evaluates positive psychological well-being. WHO-5 consists of 5 questions and each is rated on a 6-point scale. The total score ranges from 0 to 25 (0= worst possible quality of life; 25=best possible quality of life). |
| Time Frame | Baseline and Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 222 | 224 | 221 |
| Mean (Standard Error) [Units on a scale] |
2.96
(0.36)
|
4.51
(0.35)
|
3.73
(0.36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.54 | |
| Confidence Interval |
(2-Sided) 95% -2.53 to -0.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using ANCOVA on the change from baseline with treatment as a factor and corresponding baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.129 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.77 | |
| Confidence Interval |
(2-Sided) 95% -1.75 to 0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Sexual Dysfunction at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | ASEX scale includes 5 questions that evaluate sexual function exclusively during the week prior to completion in the following areas: libido, excitability and ability to reach orgasm. Sexual dysfunction=an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. Participants who have had no sexual activity during the prior week were instructed to not complete questions 3 through 5. |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants randomly assigned to treatment who had taken at least 1 dose of double-blind study drug. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 221 | 222 | 220 |
| Number [Percentage of Participants] |
52.0
23.3%
|
48.6
21.5%
|
59.5
26.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment and gender as factors and baseline sexual dysfunction status as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3097 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.800 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 1.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | Analysis was conducted using a logistic regression model with treatment and gender as factors and baseline sexual dysfunction status as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2794 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.272 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 1.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) |
|---|---|
| Description | C-SSRS mapped into C-CASA(1-7) to assess whether participant:completed suicide(1),suicide attempt(2)(response of "Yes" on "Actual Attempt"),preparatory acts toward imminent suicidal behavior (3)("Yes" on "Preparatory Acts or Behavior"),suicidal ideation (4)("Yes" on "Wish to be dead","Non-Specific Active Suicidal Thoughts","Active Suicidal Ideation with methods without Intent to Act or Some Intent to Act,without Specific Plan or with Specific Plan and Intent),any suicidal behavior or ideation,self-injurious behaviour(7)("Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior"). |
| Time Frame | Week 8 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants randomly assigned to treatment who had taken at least 1 dose of double-blind study drug. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Suicide attempt |
0
0%
|
1
0.4%
|
0
0%
|
| Preparatory acts toward imminent suicidal behavior |
0
0%
|
0
0%
|
1
0.4%
|
| Suicidal ideation |
56
25.1%
|
43
19%
|
45
20.1%
|
| Any suicidal behavior and/or ideation |
56
25.1%
|
43
19%
|
45
20.1%
|
| Self-injurious behavior, no suicidal intent |
1
0.4%
|
0
0%
|
0
0%
|
| Title | Discontinuation-Emergent Signs and Symptoms (DESS) |
|---|---|
| Description | DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of new symptoms and old (but worse) symptoms that appeared during tapering of the test article. A higher score indicates more symptoms. |
| Time Frame | Week 8 to 10 (or ET) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis included completers for exposure (those whose exposure duration was at least 53 days) among safety population. 'n' is participants who received drug and were evaluated for measure at timepoint for each group respectively. |
| Arm/Group Title | Placebo | DVS SR 10 mg | DVS SR 50 mg |
|---|---|---|---|
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. |
| Measure Participants | 223 | 226 | 224 |
| Week 8 (or ET) (n=190,194,191) |
0.72
(1.81)
|
0.80
(1.78)
|
0.83
(2.05)
|
| Week 9 ( or ET + 1 week) (n=178,185,186) |
1.26
(2.78)
|
1.08
(2.31)
|
1.98
(3.29)
|
| Week 10 (or ET + 2 weeks (n=170,182,182) |
0.90
(2.30)
|
0.91
(2.24)
|
1.07
(2.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 8. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.805 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 9. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.805 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 10 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 10. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.978 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 8. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.805 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 9. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.154 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DVS SR 50 mg |
|---|---|---|
| Comments | To address the multiplicity effect inherent in these comparisons, adjusted p-values based on the false discovery rate was used at Week 10. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.805 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| 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 | Placebo | DVS SR 10 mg | DVS SR 50 mg | |||
| Arm/Group Description | Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET). | Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET. | DVS SR 50 mg daily until Day 56 (Week 8) or ET. | |||
All Cause Mortality |
||||||
| Placebo | DVS SR 10 mg | DVS SR 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo | DVS SR 10 mg | DVS SR 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/223 (1.3%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| General disorders | ||||||
| Non-cardiac chest pain | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Infections and infestations | ||||||
| Appendicitis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Scrotal abscess | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Renal and urinary disorders | ||||||
| Urinary retention | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Epididymitis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pulmonary embolism | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | DVS SR 10 mg | DVS SR 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 166/223 (74.4%) | 168/226 (74.3%) | 170/224 (75.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Leukocytosis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Lymphadenopathy | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Polycythaemia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Cardiac disorders | ||||||
| Atrioventricular block first degree | 2/223 (0.9%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Bradycardia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Cardiac hypertrophy | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Palpitations | 1/223 (0.4%) | 5/226 (2.2%) | 1/224 (0.4%) | |||
| Supraventricular extrasystoles | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Tachycardia | 2/223 (0.9%) | 1/226 (0.4%) | 4/224 (1.8%) | |||
| Ventricular extrasystoles | 2/223 (0.9%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Ear and labyrinth disorders | ||||||
| Ear discomfort | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Ear pain | 1/223 (0.4%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Hyperacusis | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Tinnitus | 1/223 (0.4%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Vertigo | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Eye disorders | ||||||
| Blepharospasm | 2/223 (0.9%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Conjunctivitis | 0/223 (0%) | 0/226 (0%) | 3/224 (1.3%) | |||
| Diabetic retinopathy | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Dry eye | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Excessive eye blinking | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Eye pain | 2/223 (0.9%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Eye pruritus | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Miosis | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Photophobia | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Photopsia | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Vision blurred | 3/223 (1.3%) | 3/226 (1.3%) | 4/224 (1.8%) | |||
| Visual impairment | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 2/223 (0.9%) | 2/226 (0.9%) | 2/224 (0.9%) | |||
| Abdominal distension | 4/223 (1.8%) | 4/226 (1.8%) | 4/224 (1.8%) | |||
| Abdominal pain | 2/223 (0.9%) | 5/226 (2.2%) | 4/224 (1.8%) | |||
| Abdominal pain upper | 6/223 (2.7%) | 3/226 (1.3%) | 3/224 (1.3%) | |||
| Chapped lips | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Constipation | 7/223 (3.1%) | 8/226 (3.5%) | 15/224 (6.7%) | |||
| Dental caries | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Diarrhoea | 17/223 (7.6%) | 20/226 (8.8%) | 19/224 (8.5%) | |||
| Diverticulum | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Dry mouth | 13/223 (5.8%) | 20/226 (8.8%) | 25/224 (11.2%) | |||
| Dyspepsia | 7/223 (3.1%) | 6/226 (2.7%) | 9/224 (4%) | |||
| Eructation | 0/223 (0%) | 3/226 (1.3%) | 0/224 (0%) | |||
| Faecaloma | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Faeces discoloured | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Faeces pale | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Flatulence | 7/223 (3.1%) | 5/226 (2.2%) | 2/224 (0.9%) | |||
| Food poisoning | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Frequent bowel movements | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Gastritis | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Gastrooesophageal reflux disease | 1/223 (0.4%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Haematochezia | 0/223 (0%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Nausea | 21/223 (9.4%) | 26/226 (11.5%) | 42/224 (18.8%) | |||
| Pancreatic cyst | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Salivary hypersecretion | 2/223 (0.9%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Toothache | 2/223 (0.9%) | 0/226 (0%) | 5/224 (2.2%) | |||
| Umbilical hernia | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Vomiting | 5/223 (2.2%) | 9/226 (4%) | 6/224 (2.7%) | |||
| Vomiting in pregnancy | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| General disorders | ||||||
| Asthenia | 2/223 (0.9%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Chest discomfort | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Chest pain | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Chills | 2/223 (0.9%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Fatigue | 8/223 (3.6%) | 10/226 (4.4%) | 16/224 (7.1%) | |||
| Feeling abnormal | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Feeling jittery | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Inflammation | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Influenza like illness | 1/223 (0.4%) | 2/226 (0.9%) | 4/224 (1.8%) | |||
| Injection site pruritus | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Irritability | 12/223 (5.4%) | 8/226 (3.5%) | 8/224 (3.6%) | |||
| Non-cardiac chest pain | 0/223 (0%) | 1/226 (0.4%) | 3/224 (1.3%) | |||
| Oedema peripheral | 1/223 (0.4%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Pain | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Pyrexia | 0/223 (0%) | 0/226 (0%) | 4/224 (1.8%) | |||
| Temperature intolerance | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Thirst | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Immune system disorders | ||||||
| Seasonal allergy | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Infections and infestations | ||||||
| Acarodermatitis | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Acute sinusitis | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Bronchitis | 3/223 (1.3%) | 2/226 (0.9%) | 3/224 (1.3%) | |||
| Bronchitis viral | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Cellulitis | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Ear infection | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Folliculitis | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Gastroenteritis | 1/223 (0.4%) | 4/226 (1.8%) | 2/224 (0.9%) | |||
| Gastroenteritis viral | 1/223 (0.4%) | 4/226 (1.8%) | 1/224 (0.4%) | |||
| Gingival infection | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| H1N1 influenza | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Infected bites | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Infected cyst | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Influenza | 7/223 (3.1%) | 8/226 (3.5%) | 5/224 (2.2%) | |||
| Meningitis viral | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Nasopharyngitis | 6/223 (2.7%) | 5/226 (2.2%) | 7/224 (3.1%) | |||
| Otitis media | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Pharyngitis | 3/223 (1.3%) | 3/226 (1.3%) | 1/224 (0.4%) | |||
| Pharyngitis streptococcal | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Pneumonia | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Pyelonephritis | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Respiratory tract infection viral | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Rhinitis | 2/223 (0.9%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Sinusitis | 2/223 (0.9%) | 3/226 (1.3%) | 2/224 (0.9%) | |||
| Tonsillitis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Tooth abscess | 2/223 (0.9%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Tooth infection | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Upper respiratory tract infection | 17/223 (7.6%) | 21/226 (9.3%) | 16/224 (7.1%) | |||
| Urinary tract infection | 4/223 (1.8%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Vaginitis bacterial | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Viral infection | 4/223 (1.8%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Viral upper respiratory tract infection | 0/223 (0%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Vulvovaginal candidiasis | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Vulvovaginal mycotic infection | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Ankle fracture | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Arthropod sting | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Back injury | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Contusion | 2/223 (0.9%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Epicondylitis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Excoriation | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Fall | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Intentional overdose | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Joint injury | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Joint sprain | 2/223 (0.9%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Ligament rupture | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Limb injury | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Meniscus lesion | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Muscle strain | 2/223 (0.9%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Procedural pain | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Road traffic accident | 0/223 (0%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Skin laceration | 2/223 (0.9%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Tooth fracture | 0/223 (0%) | 0/226 (0%) | 3/224 (1.3%) | |||
| Upper limb fracture | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/223 (0.4%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Aspartate aminotransferase increased | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood alkaline phosphatase increased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood bilirubin increased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood calcium increased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood glucose increased | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood human chorionic gonadotropin | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Blood pressure decreased | 0/223 (0%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Blood pressure diastolic decreased | 1/223 (0.4%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Blood pressure diastolic increased | 1/223 (0.4%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Blood pressure increased | 0/223 (0%) | 1/226 (0.4%) | 4/224 (1.8%) | |||
| Blood pressure orthostatic decreased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood pressure systolic decreased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Blood prolactin increased | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Blood triglycerides increased | 2/223 (0.9%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Body temperature increased | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Electrocardiogram T wave amplitude decreased | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Electrocardiogram T wave inversion | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Heart rate increased | 0/223 (0%) | 3/226 (1.3%) | 1/224 (0.4%) | |||
| Heart rate irregular | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Hepatic enzyme increased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Liver function test abnormal | 1/223 (0.4%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Neutrophil count decreased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Platelet count decreased | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Platelet count increased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Protein urine | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Tuberculin test positive | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Weight decreased | 3/223 (1.3%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Weight increased | 2/223 (0.9%) | 1/226 (0.4%) | 3/224 (1.3%) | |||
| White blood cell count decreased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Alcohol intolerance | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Decreased appetite | 9/223 (4%) | 10/226 (4.4%) | 20/224 (8.9%) | |||
| Fluid retention | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Food craving | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Glucose tolerance impaired | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Hypercalcaemia | 0/223 (0%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Hyperkalaemia | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Hypernatraemia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Hyperphagia | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Hyperproteinaemia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Increased appetite | 4/223 (1.8%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/223 (1.3%) | 4/226 (1.8%) | 1/224 (0.4%) | |||
| Arthritis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Back pain | 3/223 (1.3%) | 3/226 (1.3%) | 5/224 (2.2%) | |||
| Costochondritis | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Fibromyalgia | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Flank pain | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Joint stiffness | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Joint swelling | 1/223 (0.4%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Muscle spasms | 1/223 (0.4%) | 4/226 (1.8%) | 4/224 (1.8%) | |||
| Muscle tightness | 4/223 (1.8%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Muscle twitching | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Musculoskeletal chest pain | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Musculoskeletal discomfort | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Musculoskeletal pain | 1/223 (0.4%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Musculoskeletal stiffness | 2/223 (0.9%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Myalgia | 7/223 (3.1%) | 5/226 (2.2%) | 6/224 (2.7%) | |||
| Myokymia | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Neck pain | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Pain in extremity | 1/223 (0.4%) | 5/226 (2.2%) | 1/224 (0.4%) | |||
| Plantar fasciitis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Rotator cuff syndrome | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Sensation of heaviness | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Abdominal neoplasm | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Melanocytic naevus | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Nervous system disorders | ||||||
| Akathisia | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Cognitive disorder | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Crying | 2/223 (0.9%) | 1/226 (0.4%) | 3/224 (1.3%) | |||
| Diabetic neuropathy | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Disturbance in attention | 1/223 (0.4%) | 7/226 (3.1%) | 3/224 (1.3%) | |||
| Dizziness | 17/223 (7.6%) | 11/226 (4.9%) | 29/224 (12.9%) | |||
| Dizziness postural | 1/223 (0.4%) | 2/226 (0.9%) | 5/224 (2.2%) | |||
| Drug withdrawal headache | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Dysgeusia | 1/223 (0.4%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Dyskinesia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Exaggerated startle response | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Headache | 23/223 (10.3%) | 32/226 (14.2%) | 24/224 (10.7%) | |||
| Hypersomnia | 0/223 (0%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Hypoaesthesia | 0/223 (0%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Hypogeusia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Lethargy | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Loss of consciousness | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Memory impairment | 1/223 (0.4%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Migraine | 2/223 (0.9%) | 0/226 (0%) | 3/224 (1.3%) | |||
| Paraesthesia | 4/223 (1.8%) | 3/226 (1.3%) | 5/224 (2.2%) | |||
| Poor quality sleep | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Presyncope | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Restless legs syndrome | 3/223 (1.3%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Sedation | 1/223 (0.4%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Sinus headache | 1/223 (0.4%) | 1/226 (0.4%) | 4/224 (1.8%) | |||
| Somnolence | 12/223 (5.4%) | 10/226 (4.4%) | 13/224 (5.8%) | |||
| Syncop | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Tension headache | 8/223 (3.6%) | 7/226 (3.1%) | 11/224 (4.9%) | |||
| Tremor | 5/223 (2.2%) | 3/226 (1.3%) | 2/224 (0.9%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Pregnancy | 1/223 (0.4%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Psychiatric disorders | ||||||
| Abnormal dreams | 8/223 (3.6%) | 11/226 (4.9%) | 14/224 (6.3%) | |||
| Agitation | 0/223 (0%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Anger | 0/223 (0%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Anorgasmia | 0/223 (0%) | 2/226 (0.9%) | 3/224 (1.3%) | |||
| Anxiety | 6/223 (2.7%) | 7/226 (3.1%) | 7/224 (3.1%) | |||
| Bradyphrenia | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Bruxism | 1/223 (0.4%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Depersonalisation | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Depressed mood | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Depression | 1/223 (0.4%) | 8/226 (3.5%) | 0/224 (0%) | |||
| Derealisation | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Disorientation | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Dissociation | 2/223 (0.9%) | 3/226 (1.3%) | 1/224 (0.4%) | |||
| Distractibility | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Elevated mood | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Impulse-control disorder | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Initial insomnia | 2/223 (0.9%) | 1/226 (0.4%) | 5/224 (2.2%) | |||
| Insomnia | 14/223 (6.3%) | 16/226 (7.1%) | 20/224 (8.9%) | |||
| Libido decreased | 5/223 (2.2%) | 5/226 (2.2%) | 6/224 (2.7%) | |||
| Loss of libido | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Major depression | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Middle insomnia | 1/223 (0.4%) | 5/226 (2.2%) | 5/224 (2.2%) | |||
| Mood altered | 0/223 (0%) | 2/226 (0.9%) | 3/224 (1.3%) | |||
| Mood swings | 1/223 (0.4%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Nervousness | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Nightmare | 0/223 (0%) | 6/226 (2.7%) | 4/224 (1.8%) | |||
| Orgasm abnormal | 1/223 (0.4%) | 2/226 (0.9%) | 2/224 (0.9%) | |||
| Orgasmic sensation decreased | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Panic attack | 1/223 (0.4%) | 3/226 (1.3%) | 0/224 (0%) | |||
| Panic disorder | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Restlessness | 1/223 (0.4%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Self injurious behaviour | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Suicidal ideation | 5/223 (2.2%) | 3/226 (1.3%) | 6/224 (2.7%) | |||
| Suicide attempt | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Tearfulness | 1/223 (0.4%) | 3/226 (1.3%) | 4/224 (1.8%) | |||
| Terminal insomnia | 2/223 (0.9%) | 0/226 (0%) | 3/224 (1.3%) | |||
| Withdrawal syndrome | 8/223 (3.6%) | 12/226 (5.3%) | 16/224 (7.1%) | |||
| Renal and urinary disorders | ||||||
| Chromaturia | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Haematuria | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Incontinence | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Micturition urgency | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Nephrolithiasis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Pollakiuria | 0/223 (0%) | 3/226 (1.3%) | 2/224 (0.9%) | |||
| Polyuria | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Proteinuria | 0/223 (0%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Urge incontinence | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Urinary hesitation | 0/223 (0%) | 0/226 (0%) | 4/224 (1.8%) | |||
| Urine odour abnormal | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Reproductive system and breast disorders | ||||||
| Breast enlargement | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Breast mass | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Breast tenderness | 2/223 (0.9%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Dysmenorrhoea | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Ejaculation delayed | 1/223 (0.4%) | 2/226 (0.9%) | 2/224 (0.9%) | |||
| Erectile dysfunction | 0/223 (0%) | 2/226 (0.9%) | 3/224 (1.3%) | |||
| Menorrhagia | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Menstruation irregular | 1/223 (0.4%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Metrorrhagia | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Oligomenorrhoea | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Pelvic pain | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Prostatomegaly | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Sexual dysfunction | 0/223 (0%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Spontaneous penile erection | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Vaginal discharge | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Vaginal odour | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Atelectasis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Choking | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Cough | 3/223 (1.3%) | 2/226 (0.9%) | 2/224 (0.9%) | |||
| Dysphonia | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Dyspnoea | 2/223 (0.9%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Epistaxis | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Nasal congestion | 2/223 (0.9%) | 2/226 (0.9%) | 0/224 (0%) | |||
| Oropharyngeal pain | 1/223 (0.4%) | 5/226 (2.2%) | 2/224 (0.9%) | |||
| Rhinorrhoea | 1/223 (0.4%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Sinus congestion | 2/223 (0.9%) | 2/226 (0.9%) | 3/224 (1.3%) | |||
| Wheezing | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Yawning | 3/223 (1.3%) | 2/226 (0.9%) | 4/224 (1.8%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 0/223 (0%) | 1/226 (0.4%) | 4/224 (1.8%) | |||
| Alopecia | 3/223 (1.3%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Cold sweat | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Dermal cyst | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Dermatitis atopic | 1/223 (0.4%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Dermatitis contact | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Dry skin | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Ecchymosis | 1/223 (0.4%) | 1/226 (0.4%) | 2/224 (0.9%) | |||
| Hyperhidrosis | 11/223 (4.9%) | 11/226 (4.9%) | 12/224 (5.4%) | |||
| Hypoaesthesia facial | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Increased tendency to bruise | 0/223 (0%) | 1/226 (0.4%) | 1/224 (0.4%) | |||
| Ingrowing nail | 2/223 (0.9%) | 0/226 (0%) | 0/224 (0%) | |||
| Keloid scar | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Night sweats | 0/223 (0%) | 1/226 (0.4%) | 3/224 (1.3%) | |||
| Pruritus | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Pruritus generalised | 1/223 (0.4%) | 1/226 (0.4%) | 0/224 (0%) | |||
| Rash | 0/223 (0%) | 2/226 (0.9%) | 1/224 (0.4%) | |||
| Rash generalised | 1/223 (0.4%) | 0/226 (0%) | 0/224 (0%) | |||
| Vascular disorders | ||||||
| Haematoma | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Hot flush | 6/223 (2.7%) | 3/226 (1.3%) | 4/224 (1.8%) | |||
| Hypertension | 4/223 (1.8%) | 0/226 (0%) | 2/224 (0.9%) | |||
| Orthostatic hypertension | 0/223 (0%) | 0/226 (0%) | 1/224 (0.4%) | |||
| Systolic hypertension | 0/223 (0%) | 1/226 (0.4%) | 0/224 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00863798
Other Study ID Numbers:
- 3151A1-3362
- B2061005
- 3151A1-3362-US
First Posted:
Mar 18, 2009
Last Update Posted:
May 6, 2011
Last Verified:
Apr 1, 2011