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

Bipolar Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00277212
• Other study ID #: CN138-392 ST
• Status: Completed
• Phase: Phase 4
• First received: January 13, 2006
• Last updated: November 7, 2013
• Start date: December 2005
• Est. completion date: July 2009

Study information

• Verified date: November 2010
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1169
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

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
• Lamotrigine + Placebo
Tablets, Oral, once daily, Phase 2 - up to 52 weeks Lamotrigine 100-200 mg/day placebo 0 mg/day

Locations

Country	Name	City	State
Puerto Rico	Local Institution	Cabo Rojo
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Rio Piedras
Puerto Rico	Local Institution	San Juan
United States	Lehigh Center For Clinical Research	Allentown	Pennsylvania
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Pravin Kansagra, M.D.	Anaheim	California
United States	Comprehensive Neuroscience, Inc	Atlanta	Georgia
United States	Sheppard Pratt Health System	Baltimore	Maryland
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Horizon Medical Services	Bismarck	North Dakota
United States	Health Sciences America, Llc	Boca Raton	Florida
United States	Pacific Institute Of Medical Sciences	Bothell	Washington
United States	Buffalo Psychiatric Center	Buffalo	New York
United States	Neuro Behavioral Clinical Research, Inc.	Canton	Ohio
United States	University Of Virginia Health System	Charlottesville	Virginia
United States	University Of Medicine & Dentistry Of New Jersey	Cherry Hill	New Jersey
United States	Community Research	Cincinnati	Ohio
United States	Saroj Brar Md, Inc	Cleveland	Ohio
United States	Cns Clinical Research Group	Coral Springs	Florida
United States	College Hospital Costa Mesa	Costa Mesa	California
United States	Act Clinical Research Institute, Llc	Daytona Beach	Florida
United States	Dubois Regional Medical Center	Dubois	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Freimer, Martin	East Stroudsburg	Pennsylvania
United States	Psychopharmacology Research Corporation	Farmington Hills	Michigan
United States	Precise Research Centers	Flowood	Mississippi
United States	Neuropsychiatric Research Center Of Southwest Florida	Fort Myers	Florida
United States	Clinical Insights	Glen Burnie	Maryland
United States	Valle Vista Health System	Greenwood	Indiana
United States	Bayou City Research, Ltd.	Houston	Texas
United States	University Of Kentucky, Dept. Of Psychiatry	Lexington	Kentucky
United States	Pacific Institute For Medical Research, Inc.	Los Angeles	California
United States	Ut Medical Group/Odyssey Research	Memphis	Tennessee
United States	Aurora-Cuervo Clinical Trials	Miami	Florida
United States	Aurora Health Care	Milwaukee	Wisconsin
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Health Research Center	Morgantown	West Virginia
United States	Psychiatric Consultants, Pc	Nashville	Tennessee
United States	Excell Research	Oceanside	California
United States	Cutting Edge Research	Oklahoma City	Oklahoma
United States	University Of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Owensboro Behavioral Care	Owensboro	Kentucky
United States	Southern Ca Clinical Research, Inc.	Pasadena	California
United States	Belmont Center For Comprehensive Treatment	Philadelphia	Pennsylvania
United States	Cns Research Institute	Philadelphia	Pennsylvania
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Harmony Research, Llc	Piney Flats	Tennessee
United States	Gulf Coast Medical Research	Port Charlotte	Florida
United States	Summit Research Network	Portland	Oregon
United States	Clinical Trials Technology, Inc	Prairie Village	Kansas
United States	Zarzar Psychiatric Associates, Pllc	Raleigh	North Carolina
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Capital Clinical Research Associates	Rockville	Maryland
United States	Alamo Superior Research	San Antonio	Texas
United States	Summit Research Network (Seattle) Llc	Seattle	Washington
United States	Regions Hospital	St. Paul	Minnesota
United States	Stanford University	Stanford	California
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Clinco	Terre Haute	Indiana
United States	Los Angeles Biomedical Research Institute	Torrance	California
United States	Southwest Biomedical Research Foundation	Tucson	Arizona
United States	Pacific Clinical Research Medical Group	Upland	California
United States	Windwood Centre	Virginia Beach	Virginia
United States	Janus Center For Psychiatric Research	West Palm Beach	Florida
United States	Clinical Research Institute	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Otsuka America Pharmaceutical

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2)	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	No
Secondary	Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2	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	No
Secondary	Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2)	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	No
Secondary	Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2)	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	No
Secondary	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	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)	Yes
Secondary	Adjusted Mean Change From Baseline in Body Weight, Phase 2	Adjusted for index mood episode and baseline assessment	Baseline, Week 52	Yes
Secondary	Number of Participants Showing Clinically Relevant Weight Loss by Study Week	Weight Loss of at least a 7% decrease from Baseline.	Weeks 12, 24, 36, 52	Yes
Secondary	Number of Participants Showing Clinically Relevant Weight Gain by Study Week	Weight gain of at least a 7% increase from Baseline.	Weeks 12, 24, 36, 52	Yes
Secondary	Adjusted Mean Change From Baseline in BMI by Study Week	Adjusted for index mood episode and baseline assessment.	Baseline, Weeks 12, 24, 36, 52	Yes
Secondary	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment	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	Yes
Secondary	Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment	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	Yes
Secondary	Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)	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	Yes
Secondary	Summary of Concomitant Medications, Phase 1		Phase 1 (9 to 24 Week Single-blind Stabilization Phase)	Yes
Secondary	Summary of Concomitant Medications, Phase 2		Phase 2 (52 Week Double-blind Relapse Assessment Phase)	Yes
Secondary	Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score	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	Yes
Secondary	Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score	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	Yes
Secondary	Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment,	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	Yes

External Links

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