Venlafaxine ER Long-Term Extension Study for Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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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.

Official Title
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A Open-label Long-term Extension Study To Evaluate The Safety And Efficacy Of Venlafaxine Er In Adult Outpatients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Venlafaxine ER


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venlafaxine ER<br> | Drug: Venlafaxine ER<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]) up to 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| 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. | Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 | 
| 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. | Baseline (Week 8 of the preceding double-blind study B2411263 [NCT01441440]), Weeks 12, 24, 44 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venlafaxine ER, long-term extension, Japan