Major Depressive Disorder
Conditions
Keywords
Venlafaxine ER, long-term extension, Japan
Brief summary
This is a phase 3, flexible-dose, open-label, multi-center study. The subjects who complete the week 8 visit in the prior double-blind study (B2411263) will be eligible to participate in this study. This study consists of 10 month treatment phase and 1-3 week tapering phase. The 2 follow-up visits will be evaluated after 2 weeks and 4 weeks of last study medication dosing.
Interventions
DRUGVenlafaxine ER
Treatment phase: 10 months (75-225 mg/day), oral administration Tapering phase: 1-3 weeks (stepwise dose reduction: 150-37.5 mg/day), oral administration
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients who have completed 8 weeks double-blind study (B2411263), without major protocol violations or tolerability concerns in the opinion of the investigator.
Exclusion criteria
* Clinically important abnormalities on baseline (Week 8 of the double-blind study) physical examination, or any unresolved clinically significant abnormalities on electrocardiogram (ECG), laboratory test results, or vital signs recorded before Week 8 in the previous double-blind study. * Significant risk of suicide based on clinical judgment. * Use of prohibited treatments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 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. |
| Number of Participants With Clinical Significant Vital Changes | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 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. |
| Number of Participants With Clinical Significant Laboratory Tests Changes | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 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. |
| Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point | 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, 44 | 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. |
| Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline Time Point | Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 | 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. |
| Change From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) at Each Post Baseline Time Point | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 12, 24, 44 | 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. |
| Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point | 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, 44 | 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. |
Countries
Japan
Participant flow
Pre-assignment details
Participants who have completed the week 8 visit in the preceding double-blind study B2411263 (NCT01441440) were eligible to participate in this study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Deterioration of primary disease | 1 |
| Overall Study | Primary disease markedly improved | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Venlafaxine ER 75-225 mg/Day Flexible |
|---|---|
| Age, Continuous | 43.7 years STANDARD_DEVIATION 13.6 |
| Sex: Female, Male FEMALE | 26 Participants |
| Sex: Female, Male MALE | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 50 |
| serious Total, serious adverse events | 2 / 50 |
Outcome results
Primary
Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes
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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Population: Participants with at least one observation of the electrocardiogram while on study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QT Interval > 450 ms | 5 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QT Interval > 480 ms | 0 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QT Interval > 500 ms | 0 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcB Interval > 500 ms | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcB Interval > 450 ms | 17 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcB Interval > 480 ms | 4 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcF Interval > 450 ms | 8 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcF Interval > 480 ms | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcF Interval > 500 ms | 0 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QT Interval increase from baseline >= 30 ms | 7 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QT Interval increase from baseline >= 60 ms | 0 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcB Interval increase from baseline >= 30 ms | 8 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcB Interval increase from baseline >= 60 ms | 0 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcF Interval increase from baseline >= 30 ms | 4 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Electrocardiogram (ECG) Changes | QTcF Interval increase from baseline >= 60 ms | 0 Participants |
Primary
Number of Participants With Clinical Significant Laboratory Tests Changes
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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Population: Participants with at least one observation of the given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Red Blood Cell Count < 0.8xLLN | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Lymphocytes (%) < 0.8xLLN | 2 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Eosinophils (%) > 1.2xULN | 3 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Total Bilirubin > 1.5xULN | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | ALT > 3.0xULN | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | GGT > 3.0xULN | 4 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Uric Acid > 1.2xULN | 1 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Cholesterol > 1.3xULN | 4 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | LDL Cholestero l> 1.2xULN | 12 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Triglycerides > 1.3xULN | 8 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Glucose > 1.5xULN | 3 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Urine Glucose (Qual) >= 1 | 3 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Urine Protein (Qual) >= 1 | 3 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Laboratory Tests Changes | Urine Blood/Hgb(Qual) >= 1 | 10 Participants |
Primary
Number of Participants With Clinical Significant Vital Changes
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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Population: Participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Vital Changes | Systoloc blood pressure (SBP) | 3 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Vital Changes | Diastolic bloodpressure (DBP) | 4 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Clinical Significant Vital Changes | Pulse rate | 1 Participants |
Primary
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
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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Population: Participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months
Population: Participants who recieved at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) | 49 Participants |
| Venlafaxine ER 75-225 mg/Day Flexible | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events (SAEs) | 2 Participants |
Secondary
Change From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) at Each Post Baseline 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.
Time frame: Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 12, 24, 44
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
Secondary
Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline 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.
Time frame: 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, 44
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point | Week 1 (n=50) | -1.0 Units on a scale | Standard Deviation 2 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline 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.
Time frame: 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, 44
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 1.2 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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
Mean Clinical Global Impression - Improvement (CGI-I) Score at Each Post Baseline 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.
Time frame: Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 1.2 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |
| Venlafaxine ER 75-225 mg/Day Flexible | 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 |