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
- Conditions
- Bipolar Disorder
- Interventions
- Registration Number
- NCT00277212
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1169
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A1 Lamotrigine + Aripiprazole Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole ; Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole A2 Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
- Primary Outcome Measures
Name Time Method Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) 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).
- Secondary Outcome Measures
Name Time Method 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 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.
Adjusted Mean Change From Baseline in Body Weight, Phase 2 Baseline, Week 52 Adjusted for index mood episode and baseline assessment
Number of Participants Showing Clinically Relevant Weight Loss by Study Week Weeks 12, 24, 36, 52 Weight Loss of at least a 7% decrease from Baseline.
Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 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).
Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) 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).
Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) 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).
Adjusted Mean Change From Baseline in BMI by Study Week Baseline, Weeks 12, 24, 36, 52 Adjusted for index mood episode and baseline assessment.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment 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.
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment 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.
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) 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)
Summary of Concomitant Medications, Phase 1 Phase 1 (9 to 24 Week Single-blind Stabilization Phase) Summary of Concomitant Medications, Phase 2 Phase 2 (52 Week Double-blind Relapse Assessment Phase) Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score 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.
Number of Participants Showing Clinically Relevant Weight Gain by Study Week Weeks 12, 24, 36, 52 Weight gain of at least a 7% increase from Baseline.
Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score 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.
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, 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.
Trial Locations
- Locations (63)
Sheppard Pratt Health System
🇺🇸Baltimore, Maryland, United States
Neuro Behavioral Clinical Research, Inc.
🇺🇸Canton, Ohio, United States
Belmont Center For Comprehensive Treatment
🇺🇸Philadelphia, Pennsylvania, United States
Lehigh Center For Clinical Research
🇺🇸Allentown, Pennsylvania, United States
University Of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Cns Research Institute
🇺🇸Philadelphia, Pennsylvania, United States
Comprehensive Neuroscience, Inc
🇺🇸Atlanta, Georgia, United States
Aurora-Cuervo Clinical Trials
🇺🇸Miami, Florida, United States
Community Research
🇺🇸Cincinnati, Ohio, United States
Bayou City Research, Ltd.
🇺🇸Houston, Texas, United States
Summit Research Network (Seattle) Llc
🇺🇸Seattle, Washington, United States
Southwest Biomedical Research Foundation
🇺🇸Tucson, Arizona, United States
Neuropsychiatric Research Center Of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Act Clinical Research Institute, Llc
🇺🇸Daytona Beach, Florida, United States
Gulf Coast Medical Research
🇺🇸Port Charlotte, Florida, United States
Clinical Insights
🇺🇸Glen Burnie, Maryland, United States
Excell Research
🇺🇸Oceanside, California, United States
Pacific Institute Of Medical Sciences
🇺🇸Bothell, Washington, United States
Horizon Medical Services
🇺🇸Bismarck, North Dakota, United States
Los Angeles Biomedical Research Institute
🇺🇸Torrance, California, United States
University Of Kentucky, Dept. Of Psychiatry
🇺🇸Lexington, Kentucky, United States
Health Sciences America, Llc
🇺🇸Boca Raton, Florida, United States
Owensboro Behavioral Care
🇺🇸Owensboro, Kentucky, United States
Regions Hospital
🇺🇸St. Paul, Minnesota, United States
Pacific Institute For Medical Research, Inc.
🇺🇸Los Angeles, California, United States
Pacific Clinical Research Medical Group
🇺🇸Upland, California, United States
Pravin Kansagra, M.D.
🇺🇸Anaheim, California, United States
Stanford University
🇺🇸Stanford, California, United States
Southern Ca Clinical Research, Inc.
🇺🇸Pasadena, California, United States
College Hospital Costa Mesa
🇺🇸Costa Mesa, California, United States
Cns Clinical Research Group
🇺🇸Coral Springs, Florida, United States
Clinical Research Institute
🇺🇸Wichita, Kansas, United States
Buffalo Psychiatric Center
🇺🇸Buffalo, New York, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Clinical Trials Technology, Inc
🇺🇸Prairie Village, Kansas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University Of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Cutting Edge Research
🇺🇸Oklahoma City, Oklahoma, United States
Alamo Superior Research
🇺🇸San Antonio, Texas, United States
University Of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States
University Of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Summit Research Network
🇺🇸Portland, Oregon, United States
Psychiatric Consultants, Pc
🇺🇸Nashville, Tennessee, United States
Janus Center For Psychiatric Research
🇺🇸West Palm Beach, Florida, United States
Valle Vista Health System
🇺🇸Greenwood, Indiana, United States
Clinco
🇺🇸Terre Haute, Indiana, United States
Capital Clinical Research Associates
🇺🇸Rockville, Maryland, United States
Psychopharmacology Research Corporation
🇺🇸Farmington Hills, Michigan, United States
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
Finger Lakes Clinical Research
🇺🇸Rochester, New York, United States
Zarzar Psychiatric Associates, Pllc
🇺🇸Raleigh, North Carolina, United States
Saroj Brar Md, Inc
🇺🇸Cleveland, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Ut Medical Group/Odyssey Research
🇺🇸Memphis, Tennessee, United States
Freimer, Martin
🇺🇸East Stroudsburg, Pennsylvania, United States
Dubois Regional Medical Center
🇺🇸Dubois, Pennsylvania, United States
Harmony Research, Llc
🇺🇸Piney Flats, Tennessee, United States
Windwood Centre
🇺🇸Virginia Beach, Virginia, United States
Health Research Center
🇺🇸Morgantown, West Virginia, United States
University Of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Local Institution
🇵🇷San Juan, Puerto Rico
Aurora Health Care
🇺🇸Milwaukee, Wisconsin, United States
University Of Medicine & Dentistry Of New Jersey
🇺🇸Cherry Hill, New Jersey, United States