Trial Outcomes & Findings for Venlafaxine ER Long-Term Extension Study for Major Depressive Disorder (MDD) (NCT NCT01485887)
NCT ID: NCT01485887
Last Updated: 2021-01-28
Results Overview
Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events: those which occurred or worsened after baseline. An AE resulting in any of the following outcomes, was considered to be a serious adverse event: death; lifethreatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
50 participants
Primary outcome timeframe
Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Results posted on
2021-01-28
Participant Flow
Participants who have completed the week 8 visit in the preceding double-blind study B2411263 (NCT01441440) were eligible to participate in this study.
Participant milestones
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
|
Overall Study
STARTED
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50
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Overall Study
COMPLETED
|
38
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|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
|
Overall Study
Withdrawal by Subject
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2
|
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Overall Study
Adverse Event
|
8
|
|
Overall Study
Deterioration of primary disease
|
1
|
|
Overall Study
Primary disease markedly improved
|
1
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Baseline Characteristics
Venlafaxine ER Long-Term Extension Study for Major Depressive Disorder (MDD)
Baseline characteristics by cohort
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Age, Continuous
|
43.7 years
STANDARD_DEVIATION 13.6 • n=5 Participants
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Sex: Female, Male
FEMALE
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26 Participants
n=5 Participants
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Sex: Female, Male
MALE
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 monthsPopulation: Participants who recieved at least one dose of the study drug.
Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events: those which occurred or worsened after baseline. An AE resulting in any of the following outcomes, was considered to be a serious adverse event: death; lifethreatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events (AEs)
|
49 Participants
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|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Serious adverse events (SAEs)
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2 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 monthsPopulation: Participants who received at least one dose of the study drug.
Clinical significant changes were pre-defined for systolic blood pressure (SBP), diastolic blood pressure (DBP) , and pulse rate (PR). An average value of 3 measurements in each visit meeting the following criteria for 3 consecutive visits was determined as clinical siginificant changes: DBP \>= 90 mmHg with change from the baseline \>= 10 mmHg; SBP \>= 140 mmHg with change from the baseline \>= 20 mmHg; PR \>= 100 bpm with change from the baseline \>= 15 bpm.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Number of Participants With Clinical Significant Vital Changes
Systoloc blood pressure (SBP)
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3 Participants
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|
Number of Participants With Clinical Significant Vital Changes
Diastolic bloodpressure (DBP)
|
4 Participants
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|
Number of Participants With Clinical Significant Vital Changes
Pulse rate
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1 Participants
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PRIMARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 monthsPopulation: Participants with at least one observation of the given laboratory test while on study treatment or during lag time.
Clinical significant changes were pre-defined for each laboratory test based on the criteria: Red Blood Cell Count \<0.8 x lower limit normal (LLN); Lymphocytes (%) \<0.8 x LLN; Eosinophils (%) \>1.2 x upper limit normal (ULN); Total Bilirubin \>1.5 x ULN; Alanine Aminotransferase (ALT) \>3.0 x ULN; Gamma glutamyl transferase (GGT) \>3.0 x ULN; Uric Acid \>1.2 x ULN; Cholesterol \>1.3 x ULN; Low density lipoprotein (LDL) cholesterol \>1.2 x ULN; Triglycerides \>1.3 x ULN; Glucose \>1.5 x ULN; Urine Glucose \[qualitative (Qual)\] \>=1; Urine Protein (Qual) \>=1; Urine Blood/Hemoglobin (Hgb) (Qual) \>=1.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=49 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Number of Participants With Clinical Significant Laboratory Tests Changes
Red Blood Cell Count < 0.8xLLN
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1 Participants
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Number of Participants With Clinical Significant Laboratory Tests Changes
Lymphocytes (%) < 0.8xLLN
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2 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Eosinophils (%) > 1.2xULN
|
3 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Total Bilirubin > 1.5xULN
|
1 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
ALT > 3.0xULN
|
1 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
GGT > 3.0xULN
|
4 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Uric Acid > 1.2xULN
|
1 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Cholesterol > 1.3xULN
|
4 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
LDL Cholestero l> 1.2xULN
|
12 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Triglycerides > 1.3xULN
|
8 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Glucose > 1.5xULN
|
3 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Urine Glucose (Qual) >= 1
|
3 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Urine Protein (Qual) >= 1
|
3 Participants
|
|
Number of Participants With Clinical Significant Laboratory Tests Changes
Urine Blood/Hgb(Qual) >= 1
|
10 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 monthsPopulation: Participants with at least one observation of the electrocardiogram while on study treatment.
Clinically significant ECG findings included: corrected QT (QTc), QT interval corrected using the Bazett's formula (QTcB), and QT interval corrected using the Fridericia formula (QTcF)\> 450 millisecond (ms), \>480 ms, and \>500 ms respsctively, change from baseline in QTc, QTcB, and QTcF \>= 30 ms, and \>= 60 ms, respectively.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=49 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QT Interval > 450 ms
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5 Participants
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Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QT Interval > 480 ms
|
0 Participants
|
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Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QT Interval > 500 ms
|
0 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcB Interval > 450 ms
|
17 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcB Interval > 480 ms
|
4 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcB Interval > 500 ms
|
1 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcF Interval > 450 ms
|
8 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcF Interval > 480 ms
|
1 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcF Interval > 500 ms
|
0 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QT Interval increase from baseline >= 30 ms
|
7 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QT Interval increase from baseline >= 60 ms
|
0 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcB Interval increase from baseline >= 30 ms
|
8 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcB Interval increase from baseline >= 60 ms
|
0 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcF Interval increase from baseline >= 30 ms
|
4 Participants
|
|
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
QTcF Interval increase from baseline >= 60 ms
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 monthsPopulation: Participants who received at least one dose of the study drug.
C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Number of Participants With no at Baseline and Yes at Any Post Baseline for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories
Suicide attempt
|
0 Participants
|
|
Number of Participants With no at Baseline and Yes at Any Post Baseline for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories
Preparatory acts toward imminent suicidal behavior
|
0 Participants
|
|
Number of Participants With no at Baseline and Yes at Any Post Baseline for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories
Suicide ideation
|
0 Participants
|
|
Number of Participants With no at Baseline and Yes at Any Post Baseline for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories
Self-injurious behavior, no suicidal intent
|
0 Participants
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|
Number of Participants With no at Baseline and Yes at Any Post Baseline for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories
Completed suicide
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44Population: Participants who recieved at least one dose of study drug in this study , and had at least one evaluable HAM-D17 score after Week 8 of the preceding study B2411263 (NCT01441440). 'n' is signifying those participants who were evaluated for this measure at each time point.
HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAM-D17 are rated on a scale of 0 to 2 (8 items) or 0 to 4 (9 items), and the total score ranges from 0 to 52. Higher scores indicate more severe symptoms. Change from baseline: mean score at observation minus mean score at baseline.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 1 (n=50)
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-1.0 Units on a scale
Standard Deviation 2.00
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Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 2 (n=50)
|
-1.5 Units on a scale
Standard Deviation 3.47
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Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 3 (n=50)
|
-2.2 Units on a scale
Standard Deviation 4.76
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 4 (n=50)
|
-2.9 Units on a scale
Standard Deviation 4.55
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 12 (n=47)
|
-4.1 Units on a scale
Standard Deviation 5.41
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 28 (n=42)
|
-6.1 Units on a scale
Standard Deviation 5.67
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 32 (n=41)
|
-6.4 Units on a scale
Standard Deviation 5.81
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 6 (n=47)
|
-3.4 Units on a scale
Standard Deviation 4.39
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 8 (n=48)
|
-3.9 Units on a scale
Standard Deviation 4.61
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 16 (n=46)
|
-4.4 Units on a scale
Standard Deviation 7.06
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 20 (n=45)
|
-6.2 Units on a scale
Standard Deviation 4.93
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 24 (n=44)
|
-5.7 Units on a scale
Standard Deviation 5.08
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 36 (n=41)
|
-6.5 Units on a scale
Standard Deviation 5.85
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 40 (n=40)
|
-6.4 Units on a scale
Standard Deviation 6.55
|
|
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point
Week 44 (n=40)
|
-7.1 Units on a scale
Standard Deviation 5.98
|
SECONDARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44Population: Participants who recieved at least one dose of study drug in this study , and had at least one evaluable HAM-D17 score after Week 8 of the preceding study B2411263 (NCT01441440). 'n' is signifying those participants who were evaluated for this measure at each time point.
CGI-S is a 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states. Change from baseline: mean score at observation minus mean score at baseline.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
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|---|---|
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Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 6 (n=47)
|
-0.6 Units on a scale
Standard Deviation 0.77
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 1 (n=50)
|
-0.1 Units on a scale
Standard Deviation 0.46
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 2 (n=50)
|
-0.3 Units on a scale
Standard Deviation 0.63
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 3 (n=50)
|
-0.3 Units on a scale
Standard Deviation 0.87
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 4 (n=50)
|
-0.4 Units on a scale
Standard Deviation 0.81
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 8 (n=48)
|
-0.6 Units on a scale
Standard Deviation 0.91
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 12 (n=47)
|
-0.8 Units on a scale
Standard Deviation 1.20
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 16 (n=46)
|
-0.9 Units on a scale
Standard Deviation 1.34
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 20 (n=45)
|
-1.2 Units on a scale
Standard Deviation 0.98
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 24 (n=44)
|
-1.1 Units on a scale
Standard Deviation 1.01
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 28 (n=42)
|
-1.2 Units on a scale
Standard Deviation 1.07
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 32 (n=41)
|
-1.2 Units on a scale
Standard Deviation 1.11
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 36 (n=41)
|
-1.2 Units on a scale
Standard Deviation 1.19
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 40 (n=40)
|
-1.2 Units on a scale
Standard Deviation 1.23
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point
Week 44 (n=40)
|
-1.3 Units on a scale
Standard Deviation 1.12
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44Population: Participants who recieved at least one dose of study drug in this study , and had at least one evaluable HAM-D17 score after Week 8 of the preceding study B2411263 (NCT01441440). 'n' is signifying those participants who were evaluated for this measure at each time point.
CGI-I is a 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 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. Scores above 4 reflect worsening of illness state as compared to baseline.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
|
|---|---|
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Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 4 (n=50)
|
3.1 Units on a scale
Standard Deviation 1.05
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 6 (n=47)
|
2.9 Units on a scale
Standard Deviation 0.91
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 44 (n=40)
|
2.0 Units on a scale
Standard Deviation 1.15
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 32 (n=41)
|
2.1 Units on a scale
Standard Deviation 1.14
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 36 (n=41)
|
2.2 Units on a scale
Standard Deviation 1.18
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 40 (n=40)
|
2.1 Units on a scale
Standard Deviation 1.25
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 1 (n=50)
|
3.8 Units on a scale
Standard Deviation 0.62
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 2 (n=50)
|
3.5 Units on a scale
Standard Deviation 0.81
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 3 (n=50)
|
3.3 Units on a scale
Standard Deviation 1.05
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 8 (n=48)
|
2.9 Units on a scale
Standard Deviation 0.96
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 12 (n=47)
|
2.6 Units on a scale
Standard Deviation 1.06
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 16 (n=46)
|
2.4 Units on a scale
Standard Deviation 1.20
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 20 (n=45)
|
2.1 Units on a scale
Standard Deviation 0.97
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 24 (n=44)
|
2.2 Units on a scale
Standard Deviation 1.05
|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point
Week 28 (n=42)
|
2.2 Units on a scale
Standard Deviation 1.09
|
SECONDARY outcome
Timeframe: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 12, 24, 44Population: Participants who recieved at least one dose of study drug in this study , and had at least one evaluable HAM-D17 score and QIDS16-SR-J score after Week 8 of the preceding study B2411263 (NCT01441440). 'n' is signifying those participants who were evaluated for this measure at each time point.
QIDS16-SR-J is a self-rated scale used in patients with major depressive disorder to measure the overall severity of depressive symptoms: 1) sad mood; 2) concentration; 3) self-criticism; 4) suicidal ideation; 5) interest; 6) energy/fatigue; 7) sleep disturbance (initial, middle, and late insomnia or hypersomnia); 8) decrease/increase in appetite/weight; and 9) psychomotor agitation/retardation. QIDS16-SR-J items are rated on a scale of 0 to 3, and the total score ranges from 0 to 27. Higher scores indicate more severe symptoms. Change from baseline: mean score at observation minus mean score at baseline.
Outcome measures
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=49 Participants
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
|
|---|---|
|
Change From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) at Each Post Baseline Time Point
Week 12 (n=47)
|
-2.7 Units on a scale
Standard Deviation 4.97
|
|
Change From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) at Each Post Baseline Time Point
Week 24 (n=44)
|
-3.8 Units on a scale
Standard Deviation 4.45
|
|
Change From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) at Each Post Baseline Time Point
Week 44 (n=40)
|
-4.7 Units on a scale
Standard Deviation 4.73
|
Adverse Events
Venlafaxine ER 75-225 mg/Day Flexible
Serious events: 2 serious events
Other events: 49 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 participants at risk
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
|
|---|---|
|
General disorders
Pyrexia
|
2.0%
1/50
|
|
Social circumstances
Crime
|
2.0%
1/50
|
Other adverse events
| Measure |
Venlafaxine ER 75-225 mg/Day Flexible
n=50 participants at risk
Participants orally received venlafaxine ER once daily after dinner or breakfast at a dosage within the predetermined range (75, 150, and 225 mg/day). Participants commenced venlafaxine ER treatment at the dosage of 37.5 mg/day, and after 1 week, increased the dosage to 75 mg/day and continued treatment for 1 week. If no tolerability issue was observed after 2 weeks by the judgment of the investigators, the dosage was increased to 150 mg/day and continued for 1 week. Furthermore, if no tolerability issue was observed after 3 weeks by the judgment of the investigators, the dosage was increased to 225 mg/day. Participants were able to remain at the same dose by the judgment of investigators if there was any tolerability concern from dose escalation. In addition, dose reduction was allowed upon occurrence of tolerability concern following dose escalation.
|
|---|---|
|
Cardiac disorders
Palpitations
|
10.0%
5/50
|
|
Ear and labyrinth disorders
Hyperacusis
|
2.0%
1/50
|
|
Ear and labyrinth disorders
Meniere's disease
|
2.0%
1/50
|
|
Ear and labyrinth disorders
Tinnitus
|
8.0%
4/50
|
|
Ear and labyrinth disorders
Vertigo
|
4.0%
2/50
|
|
Eye disorders
Blepharospasm
|
2.0%
1/50
|
|
Eye disorders
Cataract
|
2.0%
1/50
|
|
Eye disorders
Eye pruritus
|
2.0%
1/50
|
|
Eye disorders
Ocular hyperaemia
|
2.0%
1/50
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.0%
1/50
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.0%
2/50
|
|
Gastrointestinal disorders
Constipation
|
14.0%
7/50
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
2/50
|
|
Gastrointestinal disorders
Dry mouth
|
2.0%
1/50
|
|
Gastrointestinal disorders
Gastritis atrophic
|
2.0%
1/50
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.0%
3/50
|
|
Gastrointestinal disorders
Nausea
|
14.0%
7/50
|
|
Gastrointestinal disorders
Stomatitis
|
4.0%
2/50
|
|
Gastrointestinal disorders
Toothache
|
2.0%
1/50
|
|
Gastrointestinal disorders
Vomiting
|
6.0%
3/50
|
|
General disorders
Asthenia
|
2.0%
1/50
|
|
General disorders
Chest discomfort
|
4.0%
2/50
|
|
General disorders
Chest pain
|
4.0%
2/50
|
|
General disorders
Fatigue
|
2.0%
1/50
|
|
General disorders
Feeling abnormal
|
12.0%
6/50
|
|
General disorders
Irritability
|
4.0%
2/50
|
|
General disorders
Malaise
|
4.0%
2/50
|
|
General disorders
Non-cardiac chest pain
|
2.0%
1/50
|
|
General disorders
Thirst
|
8.0%
4/50
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
6.0%
3/50
|
|
Immune system disorders
Seasonal allergy
|
6.0%
3/50
|
|
Infections and infestations
Cellulitis
|
2.0%
1/50
|
|
Infections and infestations
Cystitis
|
2.0%
1/50
|
|
Infections and infestations
Epiglottitis
|
2.0%
1/50
|
|
Infections and infestations
Gastroenteritis
|
4.0%
2/50
|
|
Infections and infestations
Gastroenteritis viral
|
2.0%
1/50
|
|
Infections and infestations
Hordeolum
|
2.0%
1/50
|
|
Infections and infestations
Infectious mononucleosis
|
2.0%
1/50
|
|
Infections and infestations
Influenza
|
2.0%
1/50
|
|
Infections and infestations
Nasopharyngitis
|
40.0%
20/50
|
|
Infections and infestations
Sinusitis
|
2.0%
1/50
|
|
Injury, poisoning and procedural complications
Fall
|
6.0%
3/50
|
|
Injury, poisoning and procedural complications
Overdose
|
2.0%
1/50
|
|
Investigations
Alanine aminotransferase increased
|
4.0%
2/50
|
|
Investigations
Aspartate aminotransferase increased
|
4.0%
2/50
|
|
Investigations
Blood bilirubin increased
|
2.0%
1/50
|
|
Investigations
Blood cholesterol increased
|
4.0%
2/50
|
|
Investigations
Blood pressure increased
|
14.0%
7/50
|
|
Investigations
Electrocardiogram QT prolonged
|
4.0%
2/50
|
|
Investigations
Electrocardiogram T wave inversion
|
2.0%
1/50
|
|
Investigations
Gamma-glutamyltransferase increased
|
4.0%
2/50
|
|
Investigations
Heart rate increased
|
2.0%
1/50
|
|
Investigations
Low density lipoprotein increased
|
2.0%
1/50
|
|
Investigations
Occult blood positive
|
2.0%
1/50
|
|
Investigations
Protein urine present
|
2.0%
1/50
|
|
Investigations
Weight decreased
|
6.0%
3/50
|
|
Investigations
Weight increased
|
10.0%
5/50
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.0%
3/50
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
Hyperphagia
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.0%
2/50
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Joint contracture
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
4.0%
2/50
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.0%
3/50
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.0%
2/50
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
2.0%
1/50
|
|
Nervous system disorders
Amnesia
|
2.0%
1/50
|
|
Nervous system disorders
Dizziness
|
22.0%
11/50
|
|
Nervous system disorders
Dysarthria
|
2.0%
1/50
|
|
Nervous system disorders
Headache
|
26.0%
13/50
|
|
Nervous system disorders
Hyperaesthesia
|
2.0%
1/50
|
|
Nervous system disorders
Hypersomnia
|
2.0%
1/50
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
5/50
|
|
Nervous system disorders
Memory impairment
|
2.0%
1/50
|
|
Nervous system disorders
Migraine
|
2.0%
1/50
|
|
Nervous system disorders
Myoclonus
|
2.0%
1/50
|
|
Nervous system disorders
Retrograde amnesia
|
2.0%
1/50
|
|
Nervous system disorders
Somnolence
|
18.0%
9/50
|
|
Nervous system disorders
Tethered cord syndrome
|
2.0%
1/50
|
|
Nervous system disorders
Tremor
|
2.0%
1/50
|
|
Psychiatric disorders
Abnormal behaviour
|
2.0%
1/50
|
|
Psychiatric disorders
Acute stress disorder
|
2.0%
1/50
|
|
Psychiatric disorders
Agitation
|
4.0%
2/50
|
|
Psychiatric disorders
Depression
|
4.0%
2/50
|
|
Psychiatric disorders
Initial insomnia
|
2.0%
1/50
|
|
Psychiatric disorders
Insomnia
|
12.0%
6/50
|
|
Psychiatric disorders
Loss of libido
|
2.0%
1/50
|
|
Psychiatric disorders
Middle insomnia
|
2.0%
1/50
|
|
Psychiatric disorders
Sleep disorder
|
2.0%
1/50
|
|
Renal and urinary disorders
Nocturia
|
2.0%
1/50
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
2.0%
1/50
|
|
Reproductive system and breast disorders
Menopausal symptoms
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.0%
2/50
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Alopecia areata
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Dyshidrotic eczema
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Hand dermatitis
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.0%
2/50
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
5/50
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
2.0%
1/50
|
|
Surgical and medical procedures
Tooth extraction
|
2.0%
1/50
|
|
Vascular disorders
Hypertension
|
12.0%
6/50
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER