A Safety and Efficacy Study of JNJ26489112 in Patients With Treatment-Resistant Major Depressive Disorder

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Terminated

CT.gov ID

NCT01114698

Collaborator

(none)

Enrollment

Locations

Arms

11.1

Duration (Months)

0.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of JNJ26489112 compared with an active control (Venlafaxine XR) and placebo in patients with Treatment-Resistant Major Depressive Disorder.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Venlafaxine XR Drug: Placebo Drug: JNJ26489112	Phase 2

Detailed Description

This is a randomized (patients assigned to treatment groups by chance), double-blind (neither the study physician nor the patient will know the identification of treatment assigned), active- and placebo-controlled study to assess the efficacy and safety of JNJ26489112 in adult patients with treatment-resistant major depressive disorder (MDD). The active control used in the study is venlafaxine extended-release [XR], an antidepressant drug used to treat patients with MDD. A target of 150 patients will be randomly assigned (like flipping a coin) to 1 of 3 treatment groups with approximately 50 patients planned per treatment group. This study consists of a screening phase of up to 4 weeks, a 6-week double-blind treatment phase, and a safety follow-up period that includes a 1-week taper phase (described below). During the screening phase, patients who meet entry criteria for the study will be tapered off their current psychotropic medications (medications affecting the mind or mood or other mental processes) prior to randomization in the double-blind treatment phase of the study. In the double-blind treatment phase, patients will be randomly assigned to receive either 2 capsules of JNJ26489112, venlafaxine XR (the active comparator), or placebo (a sugar pill) once daily for 6 weeks. Upon completion of the double-blind treatment phase or when patients discontinue study drug at any time point during the double-blind treatment phase, study medication will be tapered and/or discontinued in a blinded manner over a 1-week period. A Data Monitoring Committee (DMC) made up of individuals not involved in the conduct of the study will monitor safety during the study. The primary outcome measure will be the change from baseline to end point (after 6 weeks of treatment or at the time of early withdrawal from the study) in the total score from the Montgomery-Asberg Depression Rating Scale (MADRS, a scale that physicians use to measure the severity of depression in patients and changes in depression due to antidepressant treatment). Patient safety will be monitored during the study by evaluating adverse events (side effects) reported and findings from clinical laboratory test results, 12-lead electrocardiograms (ECGs), vital sign measurements, body weight measurements and physical, neurologic, and ophthalmologic examinations performed. Blood samples for assessing pre- and post dose levels of JNJ26489112 or venlafaxine will be obtained at protocol-specified time points during the study. In addition, a blood sample will be obtained from all enrolled patients at Visit 2 for pharmacogenomics research (research to help identify genetic markers of response, to explain variability in the data, or to address emerging clinical issues). Patients will receive double-blind treatment with 2 capsules of JNJ26489112 (500 mg/day during the first 3 weeks that may be increased up to 1000 mg/day by week 4), venlafaxine XR (75 mg/day during week 1 increased to 150 mg/day during weeks 2-6]), or placebo orally (by mouth) with food once daily for 6 weeks. After 6 weeks, venlafaxine XR 150 mg/day will be tapered to one 75 mg/day capsule for 1 week and patients receiving JNJ26489112 or placebo will be switched to 1 capsule of placebo for 1 week.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Parallel Group, Active- and Placebo-Controlled Study to Assess the Efficacy and Safety of JNJ26489112 in Adult Subjects With Treatment-Resistant Major Depressive Disorder

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JNJ26489112	Drug: JNJ26489112 JNJ26489112 500 mg/day orally administered once daily as 2 capsules for the first 3 weeks, then dose may be increased to 1000 mg/day by week 4.
Active Comparator: Venlafaxine XR	Drug: Venlafaxine XR Venlafaxine XR 75 mg/day administered orally once daily as 2 capsules identical in appearance to JNJ26489112 during the first week increased to 150 mg/day during weeks 2 through 6.
Placebo Comparator: Placebo	Drug: Placebo Placebo: 2 capsules identical in appearance to JNJ26489112 and venlafaxine XR orally administered once daily for 6 weeks.

Arm

Intervention/Treatment

Experimental: JNJ26489112

Drug: JNJ26489112

JNJ26489112 500 mg/day orally administered once daily as 2 capsules for the first 3 weeks, then dose may be increased to 1000 mg/day by week 4.

Active Comparator: Venlafaxine XR

Drug: Venlafaxine XR

Venlafaxine XR 75 mg/day administered orally once daily as 2 capsules identical in appearance to JNJ26489112 during the first week increased to 150 mg/day during weeks 2 through 6.

Placebo Comparator: Placebo

Drug: Placebo

Placebo: 2 capsules identical in appearance to JNJ26489112 and venlafaxine XR orally administered once daily for 6 weeks.

Outcome Measures

Primary Outcome Measures

Change from baseline in Montgomery-Asberg Depression Rating Scale (10 item diagnostic questionnaire measuring the severity of depression) [Baseline and 6 weeks]

Secondary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [At each weekly visit during the study (screening through completion of the study [Week 7])]
Mean Change in Inventory of Depressive Symptoms (IDS) and Clinical Global Impression (CGI) [At Visits 1, 2, 4, 6, 8, and 9 (Screening, Baseline, Week 2, Week 4, Week 6, and Week 9)]
Findings from ophthalmologic examinations [Before the first dose of study drug, at Week 3, and after the last dose in the double-blind phase of the study (Week 7 or at the time of early termination from the study)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Meet Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revised (DMS-IV-TR) criteria for diagnosis of moderate or severe major depression without psychotic features
Have a score >=40 on the subject-rated Inventory of Depressive Symptoms-Self-Report - 30-item (IDS-SR30) At Screening (Visit 1) and Randomization (Visit 2)
Have a history of inadequate treatment response (as defined by failure to improve with a trial of adequate dosage and duration) with 2 antidepressants during the current episode, but no more than 4 antidepressant failures for lifetime
Be in good general health prior to study participation with no clinically relevant abnormalities as assessed by the investigator and determined by: medical history, physical examination, blood chemistry, hematology, urinalysis, and electrocardiogram (ECG)
Be within a body mass index (BMI) of >=18 and <35 kg/m2 at Screening (Visit 1)

Exclusion Criteria:

Have a DSM-IV diagnosis of current (active) generalized anxiety disorder, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa
Have a history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, or borderline personality disorders, mood disorder with postpartum onset, somatoform disorders, chronic fatigue syndrome or fibromyalgia
Have a history of previous non-response to an adequate treatment with venlafaxine XR (defined as >=6 weeks of 75 to 150 mg/day or more)
Have documented disease of the central nervous system that could interfere with the study assessments (including but not limited to: stroke, tumor, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, seizure disorder requiring current anticonvulsants, history of brain injury or trauma, or neurosyphilis)
Have a history of alcohol or substance (except nicotine and caffeine) dependence or abuse according to DSM-IV criteria in the past 12 months prior to Screening
Received an experimental drug or used an experimental medical device within 60 days before the planned start of treatment (Day 1) or have participated in 2 or more clinical studies in the previous 1 year

Contacts and Locations

Locations

	City	State	Country
1	Arcadia	California	United States
2	Escondido	California	United States
3	San Diego	California	United States
4	Hartford	Connecticut	United States
5	Atlanta	Georgia	United States
6	Naperville	Illinois	United States
7	Brooklyn	New York	United States
8	Garfield Heights	Ohio	United States
9	Oklahoma City	Oklahoma	United States
10	Dallas	Texas	United States
11	Houston	Texas	United States
12	Murray	Utah	United States
13	Salt Lake City	Utah	United States
14	Middleton	Wisconsin	United States