A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode

April 23, 2026 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

A Multicenter, Double-blind, Study of the Efficacy and Safety of Aripiprazole in Combination With Lamotrigine in the Long-term Maintenance Treatment of Patients With Bipolar I Disorder With a Recent Manic or Mixed Episode

Efficacy of Aripiprazole in Combination with Lamotrigine in the Long-Term Maintenance Treatment of Bipolar I Disorder in Outpatients with Recent Manic or Mixed Episode

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1169

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Cabo Rojo, Puerto Rico, 00623
        • Local Institution
      • Ponce, Puerto Rico, 00731
        • Local Institution
      • Rio Piedras, Puerto Rico, 00926
        • Local Institution
      • San Juan, Puerto Rico, 00918
        • Local Institution
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • University of Alabama at Birmingham
    • Arizona
      • Tucson, Arizona, United States, 85712
        • Southwest Biomedical Research Foundation
    • California
      • Anaheim, California, United States, 92801
        • Pravin Kansagra, M.D.
      • Costa Mesa, California, United States, 92627
        • College Hospital Costa Mesa
      • Los Angeles, California, United States, 90024
        • Pacific Institute For Medical Research, Inc.
      • Oceanside, California, United States, 92056
        • Excell Research
      • Pasadena, California, United States, 91106
        • Southern Ca Clinical Research, Inc.
      • Stanford, California, United States, 94305
        • Stanford University
      • Torrance, California, United States, 90502
        • Los Angeles Biomedical Research Institute
      • Upland, California, United States, 91786
        • Pacific Clinical Research Medical Group
    • Florida
      • Boca Raton, Florida, United States, 33432
        • Health Sciences America, Llc
      • Coral Springs, Florida, United States, 33065
        • CNS Clinical Research Group
      • Daytona Beach, Florida, United States, 32124
        • Act Clinical Research Institute, Llc
      • Fort Myers, Florida, United States, 33912
        • Neuropsychiatric Research Center of Southwest Florida
      • Miami, Florida, United States, 33143
        • Aurora-Cuervo Clinical Trials
      • Port Charlotte, Florida, United States, 33952
        • Gulf Coast Medical Research
      • West Palm Beach, Florida, United States, 33407
        • Janus Center For Psychiatric Research
    • Georgia
      • Atlanta, Georgia, United States, 30328
        • Comprehensive Neuroscience, Inc
    • Indiana
      • Greenwood, Indiana, United States, 46143
        • Valle Vista Health System
      • Terre Haute, Indiana, United States, 47802
        • Clinco
    • Kansas
      • Prairie Village, Kansas, United States, 66206
        • Clinical Trials Technology, Inc
      • Wichita, Kansas, United States, 67213
        • Clinical Research Institute
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • University Of Kentucky, Dept. Of Psychiatry
      • Owensboro, Kentucky, United States, 42301
        • Owensboro Behavioral Care
    • Maryland
      • Baltimore, Maryland, United States, 21285
        • Sheppard Pratt Health System
      • Glen Burnie, Maryland, United States, 21061
        • Clinical Insights
      • Rockville, Maryland, United States, 20852
        • Capital Clinical Research Associates
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Psychopharmacology Research Corporation
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Precise Research Centers
    • New Jersey
      • Cherry Hill, New Jersey, United States, 08002
        • University Of Medicine & Dentistry Of New Jersey
    • New York
      • Buffalo, New York, United States, 14213
        • Buffalo Psychiatric Center
      • Rochester, New York, United States, 14618
        • Finger Lakes Clinical Research
      • Staten Island, New York, United States, 10312
        • Richmond Behavioral Associates
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medical Center
      • Raleigh, North Carolina, United States, 27607
        • Zarzar Psychiatric Associates, Pllc
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Horizon Medical Services
    • Ohio
      • Canton, Ohio, United States, 44708
        • Neuro Behavioral Clinical Research, Inc.
      • Cincinnati, Ohio, United States, 45227
        • Community Research
      • Cleveland, Ohio, United States, 44113
        • Saroj Brar Md, Inc
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73116
        • Cutting Edge Research
    • Oregon
      • Portland, Oregon, United States, 97210
        • Summit Research Network
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18104
        • Lehigh Center For Clinical Research
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital
      • DuBois, Pennsylvania, United States, 15801
        • Dubois Regional Medical Center
      • East Stroudsburg, Pennsylvania, United States, 18301
        • Freimer, Martin
      • Philadelphia, Pennsylvania, United States, 19104
        • UNIVERSITY of PENNSYLVANIA
      • Philadelphia, Pennsylvania, United States, 19149
        • Cns Research Institute
      • Philadelphia, Pennsylvania, United States, 19131
        • Belmont Center For Comprehensive Treatment
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Ut Medical Group/Odyssey Research
      • Nashville, Tennessee, United States, 37203
        • Psychiatric Consultants, PC
      • Piney Flats, Tennessee, United States, 37686
        • Harmony Research, Llc
    • Texas
      • Houston, Texas, United States, 77007
        • Bayou City Research, Ltd.
      • San Antonio, Texas, United States, 78229
        • Alamo Superior Research
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System
      • Virginia Beach, Virginia, United States, 23452
        • Windwood Centre
    • Washington
      • Bothell, Washington, United States, 98011
        • Pacific Institute of Medical Sciences
      • Seattle, Washington, United States, 98104
        • Summit Research Network (Seattle) Llc
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Health Research Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53233
        • Aurora Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women ≥ 18 years of age meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IV-TR) criteria for bipolar I disorder, recently experiencing a manic or mixed episode with a history of one or more manic or mixed episodes of sufficient severity to require treatment with a mood stabilizer or antipsychotic

Exclusion Criteria:

  • First manic episode
  • Current manic or mixed episode with > 2 years duration
  • Treated with aripiprazole within the past 3 months
  • Allergic, intolerant, hypersensitive or refractory to aripiprazole or lamotrigine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A1
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole ; Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Drug: Lamotrigine + Aripiprazole

Tablets, Oral, once daily, Phase 1 (all subjects) - up to 24 weeks; Phase 2 - up to 52 weeks

Lamotrigine 100-200 mg/day

Aripiprazole 10-30 mg/day

Other Names:
  • Abilify
  • BMS-337039
Placebo Comparator: A2
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
Drug: Lamotrigine + Placebo

Tablets, Oral, once daily, Phase 2 - up to 52 weeks

Lamotrigine 100-200 mg/day

placebo 0 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2)
Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Time from randomization to relapse to a manic or mixed episode in the Double-Blind Relapse Assessment Phase as measured by the Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2
Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2)
Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2)
Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants without Discontinuation Through Week 52(Kaplan-Meier's estimated survival rate).
Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation of Study Medication, Treatment-Emergent AEs and Treatment-Emergent Extrapyramidal Syndrome (EPS)-Related AEs
Time Frame: Throughout Phase 2 (up to 52 weeks)
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Throughout Phase 2 (up to 52 weeks)
Adjusted Mean Change From Baseline in Body Weight, Phase 2
Time Frame: Baseline, Week 52
Adjusted for index mood episode and baseline assessment
Baseline, Week 52
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Time Frame: Weeks 12, 24, 36, 52
Weight Loss of at least a 7% decrease from Baseline.
Weeks 12, 24, 36, 52
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Time Frame: Weeks 12, 24, 36, 52
Weight gain of at least a 7% increase from Baseline.
Weeks 12, 24, 36, 52
Adjusted Mean Change From Baseline in BMI by Study Week
Time Frame: Baseline, Weeks 12, 24, 36, 52
Adjusted for index mood episode and baseline assessment.
Baseline, Weeks 12, 24, 36, 52
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Time Frame: Throughout the study, up to Week 52
Abbreviations and further description used in table: Sinus tachycardia, ≥120 beats per minute (bpm) and ↑ ≥15 bpm & no current diagnosis of supraventricular or ventricular tachycardia/atrial fibrillation (AF)/atrial flutter/ other rhythm abnormality. Sinus bradycardia, ≤ 50 bpm and ↓ 15 bpm & no current diagnosis of AF/atrial flutter/other rhythm abnormality. Supraventricular premature beat (SPB), Ventricular premature beat (VPB), Atroventricular (A-V). Other intraventricular block, QRS ≥0.12 sec and ↑ ≥0.02 sec & no current diagnosis of left or right bundle branch block.
Throughout the study, up to Week 52
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Time Frame: Up to 52 Weeks
In order to be identified as clinically relevant abnormal, an on-drug value must meet the Criterion Value (CV) and also represent a change from the patient's pretreatment value of at least the Change Relative to Baseline (CRB) magnitude. Heart Rate CV: 120 beats per minute (bpm), CRB: increase of ≥15 / CV: 50 bpm, CRB: decrease of ≥15. Systolic BP CV: 180 mmHg, CRB: increase of ≥20 / CV: 90 mmHg, CRB: decrease of ≥20. Diastolic BP CV: 105 mmHg, CRB: increase of ≥15 / CV: 50 mmHg, CRB: decrease of ≥15.
Up to 52 Weeks
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Time Frame: Throughout Phase 2 of the study, up to Week 52
Chemistry, hematology, and urinalysis abnormalities.Abbreviations used: alanine aminotransferase (ALT), institutional upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), baseline (BL)
Throughout Phase 2 of the study, up to Week 52
Summary of Concomitant Medications, Phase 1
Time Frame: Phase 1 (9 to 24 Week Single-blind Stabilization Phase)
Phase 1 (9 to 24 Week Single-blind Stabilization Phase)
Summary of Concomitant Medications, Phase 2
Time Frame: Phase 2 (52 Week Double-blind Relapse Assessment Phase)
Phase 2 (52 Week Double-blind Relapse Assessment Phase)
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Time Frame: Baseline, Weeks 8, 24, 36, 52
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50. Negative change scores indicate improvement.
Baseline, Weeks 8, 24, 36, 52
Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
Time Frame: Baseline, Weeks 8, 24, 36, 52
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Baseline, Weeks 8, 24, 36, 52
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment,
Time Frame: Baseline, Weeks 8, 24, 36, 52
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Baseline, Weeks 8, 24, 36, 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

Otsuka America Pharmaceutical

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2005

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

January 13, 2006

First Submitted That Met QC Criteria

January 13, 2006

First Posted (Estimated)

January 16, 2006

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CN138-392 ST

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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