Venlafaxine ER Phase 3 Study for Major Depressive Disorder (MDD)

A Randomized, Double-blind, Placebo Controlled, Multicenter Study To Evaluate The Efficacy And Safety Of Venlafaxine Er In Adult Outpatients With Major Depressive Disorder

This is a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of venlafaxine ER 75 mg/day (fixed dose) and venlafaxine ER 75 mg/day to 225 mg/day (flexible dose), compared to placebo. This study consists of 2 week screening phase, 8 week treatment phase and 2 week tapering phase. The follow-up visit will be evaluated after 2 weeks of last study medication dosing.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: venlafaxine ER 75 mg/day (fixed dose); Drug: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 538
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-0001
    • Sugahara Tenjin Clinic
  • Fukuoka, Japan, 810-0004
    • Hiro Mental Clinic Tenjinminami
  • Fukuoka, Japan, 810-0004
    • Tenjin Mental Clinic
  • Fukuoka, Japan, 810-0022
    • Medical corporation Shinseikai Kaku Mental Clinic
  • Fukuoka, Japan, 810-0035
    • Ange Psychiatric Clinic
  • Fukuoka, Japan, 810-0041
    • Stress Care Yoshimura Clinic
  • Fukuoka, Japan, 810-0801
    • Kuranari Psychiatry Clinic
  • Fukuoka, Japan, 8100041
    • Akasaka Kato Clinic
  • Fukuoka, Japan, 815-0041
    • Imato Clinic
  • Hiroshima, Japan, 731-0112
    • Tsuji Mental Clinic
  • Kanagawa, Japan, 221-0835
    • Medical Corporation Toyokokai Tawara Clinic
  • Kyoto, Japan, 616-8421
    • Sagaarashiyama-Tanaka Clinic
  • Nara, Japan, 631-0036
    • Kyo Mental Clinic
  • Osaka, Japan, 530-0041
    • JIN clinic
  • Saitama, Japan, 341-0018
    • Misato Ekimae Clinic
  • Tokyo, Japan, 142-0021
    • Eto Mental Clinic Meguro
  • Aichi
    • Nagoya, Aichi, Japan, 458-0801
      • Narumi Himawari Clinic
    • Nagoya, Aichi, Japan, 467-0806
      • Mizuho Clinic
  • Chiba
    • Inzai, Chiba, Japan, 270-1694
      • Nippon Medical School Chiba Hokusoh Hospital
    • Nagareyama, Chiba, Japan, 270-0163
      • Hida Clinic
    • Noda City, Chiba, Japan, 278-0033
      • Nakamoto Clinic
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 814-0104
      • Hatsuki Shinryo Clinic
    • Kitakyushu-shi, Fukuoka, Japan, 802-0064
      • Hatakeyama Clinic
    • Omuta, Fukuoka, Japan, 836-0004
      • Shiranui Hospital
    • Omuta-city, Fukuoka, Japan, 836-0044
      • Oka Clinic
  • Hiroshima
    • Hatsukaichi, Hiroshima, Japan, 738-0023
      • Fujikawa Clinic
    • Kure, Hiroshima, Japan, 737-0111
      • Hayakawa Clinic
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 001-0023
      • Kawamura Mental Clinic
    • Sapporo, Hokkaido, Japan, 064-0820
      • Maruyamapark Mentalclinic
  • Hyogo
    • Amagasaki, Hyogo, Japan, 660-0882
      • Arai Clinic
    • Ashiya, Hyogo, Japan, 659-0093
      • Takahashi Psychiatric Clinic
    • Kobe, Hyogo, Japan, 651-0097
      • Tatsuta 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, Kanagawa, Japan, 252-0303
      • Yutaka Clinic
    • Yokohama-Shi, Kanagawa, Japan, 225-0011
      • Azamino Mental Clinic
    • Yokosuka city, Kanagawa, Japan, 238-0042
      • Shioiri Mental Clinic
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 861-8002
      • Yuge Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-0032
      • Kuginuki Clinic
    • Osakasayama-shi, Osaka, Japan, 589-0011
      • Shibamoto Clinic
  • Saitama
    • Saitama-city, Saitama, Japan, 330-0062
      • Sakai Mental Clinic
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0033
      • Suzuki Hospital
    • Chiyoda-ku, Tokyo, Japan, 102-0071
      • Iidabashi Mental Clinic
    • Chofu, Tokyo, Japan, 182-0006
      • Tutujigaoka Mental Clinic
    • Katsushika-ku, Tokyo, Japan, 125-0041
      • Fuku Clinic
    • Minato-ku, Tokyo, Japan, 106-0032
      • SAKURAZAKA CLINIC SophyAnce
    • Minato-ku, Tokyo, Japan, 107-0052
      • Akasaka Clinic
    • Nakano-Ku, Tokyo, Japan, 164-0001
      • Harikae mental clinic
    • Nakano-ku, Tokyo, Japan, 164-0012
      • Heartcare Ginga Clinic
    • Setagaya-ku, Tokyo, Japan, 154-0004
      • Sangenjaya Nakamura Mental Clinic
    • Setagaya-ku, Tokyo, Japan, 154-0012
      • Komazawa Mental Clinic
    • Shibuya-ku, Tokyo, Japan, 150-0001
      • Omotesando Mental Clinic
    • Shibuya-ku, Tokyo, Japan, 151-0053
      • Maynds Tower Mental Clinic
    • Shibuyaku, Tokyo, Japan, 151-0053
      • Yoyoginomori Mental Clinic
    • Shinagawa-Ku, Tokyo, Japan, 141-0032
      • Himeno Tomomi Clinic
    • Shinagawa-ku, Tokyo, Japan, 141-0021
      • Meguro sta.East Mental Clinic
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University Hospital
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Nishi-Shinjuku Concieria Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tamaki Clinic
    • Shinjuku-ku, Tokyo, Japan, 162-0825
      • Kagurazaka Stress 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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatient status.
• A primary diagnosis of MDD based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM- IV-TR), single or recurrent episode, without psychotic features.
• Depressive symptoms for at least 90 days in single episode and for at least 28 days in recurrent episode before the screening visit.
• A MADRS total score ≥26 at the screening and baseline visits. And change of MADRS total score at baseline is not over 25% from the screening visit.
• A QIDS16-J-SR score ≥16 at the screening and baseline visits.
• A score ≥4 on the Clinical Global Impressions Scale-Severity (CGI-S) at the screening and baseline visits.

Exclusion Criteria:

• Subjects who concurrently have Axis II personality disorder or mental retardation according to DSM-IV diagnostic criteria.
• Subjects who meet DSM-IV criteria for current or past history of Schizophrenia, Paranoid Disorders, or any other Psychotic Disorders.
• Subjects who meet DSM-IV criteria for current or past history of Dementia.
• Subjects who meet DSM-IV criteria for current or past history of bipolar disorder, Posttraumatic Stress Disorder (PTSD) or Obsessive Compulsive Disorder (OCD).
• Subjects who meet DSM-IV criteria for current (within 12 months before the screening visit) generalized anxiety disorder, panic disorder, or social anxiety disorder considered by the investigator to be primary (causing a higher degree of distress or impairment than MDD).
• Subjects with a first degree relative with bipolar disorder.
• Subjects who are actively suicidal.
• History of non-responsive to 2 antidepressant treatment (at least 6-week usage for each) for the past or current episodes.
• History of Electroconvulsive therapy (ECT) at any time in the past.
• History of chronic treatment with benzodiazepines for longer than 6 months before the screening visit (Excluding subjects who have taken PRN benzodiazepine use, < 3 times/week).
• Any unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, or any other medical condition that in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study.
• Known presence of raised intraocular pressure or history or presence of narrow angle glaucoma.
• Myocardial infarction within 180 days of the screening visit.
• Clinically important abnormalities, as determined by the investigator, on screening physical examination, electrocardiogram (ECG) or laboratory tests.
• Use of prohibited treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Treatment phase: 8 weeks (placebo), oral administration Tapering phase: 2 weeks (placebo), oral administration
Experimental: venlafaxine ER 75 mg/day (fixed dose)	Drug: venlafaxine ER 75 mg/day (fixed dose); Treatment phase: 8 weeks (37.5 mg/day for 1st week and 75 mg/day for 7 weeks), oral administration Tapering phase: 2 weeks (37.5 mg/day for the 1st week and placebo for the 2nd week), oral administration
Experimental: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose)	Drug: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose); Treatment phase: 8 weeks (37.5 mg/day for the 1st week, 75 mg/day for the 2nd weeks, 75-150 mg for the 3rd week, 75-225 mg/day for the rest of 5 weeks), oral administration Tapering phase: 2 weeks (75/37.5 mg/day for the 1st week and 37.5 mg/day/placebo for the 2nd week), oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 17-item Hamilton Raing Scale for Depression (HAM-D17) Total Score at Week 8 or Early Termination	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 or 0 to 4, and the total score ranges from 0 to 52. Higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.	Baseline, Week 8 or Early termination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or Early Termination	MADRS is a scale used in subjects with major depressive disorder to measure the overall severity of depressive symptoms. It is a 10 item, clinician-rated scale that assesses treatment-sensitive change by evaluating ten areas of depressive symptomatology: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. The items are rated on a 7 point Likert scale (0 - 6) with anchors at 2 point intervals. The total score ranges from 0 to 60, and higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.	Baseline, Week 8 or Early termination
Changes From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 8 or Early Termination	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 Week 8 or early termination minus mean score at baseline.	Baseline, Week 8 or Early termination
Changes From Baseline in 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score at Week 8 or Early Termination	HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.	Baseline, Week 8 or Early termination
Changes From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) Total Score at Week 8 or Early Termination	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. The total score ranges from 0 to 27, and higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.	Baseline, Week 8 or Early termination
Mean Clinical Global Impression - Improvement (CGI-I) Score at Week 8 or Early Termination	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.	Baseline, Week 8 or Early termination

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kato M, Asami Y, Wajsbrot DB, Wang X, Boucher M, Prieto R, Pappadopulos E. Clustering patients by depression symptoms to predict venlafaxine ER antidepressant efficacy: Individual patient data analysis. J Psychiatr Res. 2020 Oct;129:160-167. doi: 10.1016/j.jpsychires.2020.06.011. Epub 2020 Jul 9.
• 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: November 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 23, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Japan; placebo-controlled; Major depressive disorder; venlafaxine ER
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; 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: B2411263