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

• ClinicalTrials.gov Identifier: NCT01485887
• Recruitment Status: Completed
• First Posted: December 6, 2011
• Results First Posted: May 15, 2015
• Last Update Posted: January 28, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Tracking Information

• First Submitted Date: November 29, 2011
• First Posted Date: December 6, 2011
• Results First Submitted Date: January 9, 2015
• Results First Posted Date: May 15, 2015
• Last Update Posted Date: January 28, 2021
• Study Start Date: January 2012
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2015)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: December 2, 2011)

• Number of Participants with Adverse Events [ Time Frame: 10 months ]
• Number of Participants with clinical significant vital, laboratory tests, ECG changes [ Time Frame: 10 months ]
• Number of Participants with suicidality risk [ Time Frame: 10 months ]

Current Secondary Outcome Measures (submitted: May 13, 2015)

• Change From Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) at Each Post Baseline Time Point [ 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 ]
  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.
• Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Each Post Baseline Time Point [ 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 ]
  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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: December 2, 2011)

• Hamilton Rating Scale for Depression, 17 items (HAM-D17) total score [ Time Frame: 10 months ]
• Clinical Global Impression-Severity (CGI-S) [ Time Frame: 10 months ]
• Clinical Global Impression-Improvement (CGI-I) [ Time Frame: 10 months ]
• Quick Inventory of Depressive Symptomatology-Self Report, 16 items (QIDS16-SR-J) [ Time Frame: 10 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Venlafaxine ER Long-Term Extension Study for Major Depressive Disorder (MDD)
• Official Title: A Open-label Long-term Extension Study To Evaluate The Safety And Efficacy Of Venlafaxine Er In Adult Outpatients With Major Depressive Disorder
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

Drug: Venlafaxine 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

Study Arms

Experimental: Venlafaxine ER

Intervention: Drug: Venlafaxine ER

• Publications *: Higuchi T, Kamijima K, Nakagome K, Itamura R, Asami Y, Kuribayashi K, Imaeda T. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan. Int Clin Psychopharmacol. 2016 Jan;31(1):8-19. doi: 10.1097/YIC.0000000000000105.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 2, 2011): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2014
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01485887
• Other Study ID Numbers: B2411264
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
• Study Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2021