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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Venlafaxine ER

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-0004
    • Tenjin Mental Clinic
  • Fukuoka, Japan, 810-0041
    • Stress Care Yoshimura Clinic
  • Fukuoka, Japan, 810-0801
    • Kuranari Psychiatry Clinic
  • Kanagawa, Japan, 221-0835
    • Medical Corporation Toyokokai Tawara Clinic
  • Kyoto, Japan, 616-8421
    • Sagaarashiyama-Tanaka Clinic
  • Chiba
    • Inzai, Chiba, Japan, 270-1694
      • Nippon Medical School Chiba Hokusoh Hospital
    • Noda City, Chiba, Japan, 278-0033
      • Nakamoto Clinic
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 810-0041
      • Stress Care Yoshimura Clinic
    • Kitakyushu, Fukuoka, Japan, 802-0064
      • Hatakeyama Clinic
    • Omuta, Fukuoka, Japan, 836-0004
      • Shiranui Hospital
  • Hiroshima
    • Hatsukaichi, Hiroshima, Japan, 738-0023
      • Fujikawa Clinic
  • Hyogo
    • Ashiya, Hyogo, Japan, 659-0093
      • Takahashi Psychiatric Clinic
    • Kobe, Hyogo, Japan, 655-0037
      • Ikeuchi Psycho Induced Internal Med.Clinic
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8650
      • National Hospital Organization Kanazawa Medical Center
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 214-0014
      • Medical Corporation Seishinkai Kishiro Mental Clinic
    • Sagamihara-shi, Kanagawa, Japan, 252-0303
      • Yutaka Clinic
    • Yokohama, Kanagawa, Japan, 221-0835
      • Tawara Clinic
    • Yokosuka city, Kanagawa, Japan, 238-0042
      • Shioiri Mental Clinic
  • Osaka
    • Osakasayama-shi, Osaka, Japan, 589-0011
      • Shibamoto Clinic
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0033
      • Suzuki Hospital
    • Setagaya-ku, Tokyo, Japan, 154-0004
      • Sangenjaya Nakamura Mental Clinic
    • Shibuya-ku, Tokyo, Japan, 150-0001
      • Omotesando Mental Clinic
    • Shibuya-ku, Tokyo, Japan, 151-0053
      • Maynds Tower Mental Clinic
    • Shinjuku-ku, Tokyo, Japan, 162-8543
      • Tokyo Kosei Nenkin Hospital
    • Toshima-ku, Tokyo, Japan, 170-0002
      • Himorogi Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venlafaxine ER	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: December 2, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Japan; long-term extension; Venlafaxine ER
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
• Other Study ID Numbers: B2411264