Study to Evaluate the Efficacy and Safety of Aripiprazole Administered With Lithium or Valproate Over 12 Weeks in the Treatment of Mania in Bipolar I Disorder

Condition(s) targeted: Bipolar Disorder Mania

Intervention: Aripiprazole (Drug); Placebo (Drug); Lithium (Drug); Valproate (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Otsuka Pharmaceutical Development & Commercialization, Inc.

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

The purpose of the study is to determine whether aripiprazole provides additional clinical benefit to patients with Bipolar I disorder when combined with lithium or valproate over 12 weeks.

Official title: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate the Efficacy and Safety of Adjunctive Aripiprazole Therapy in the Treatment of Mania in Bipolar I Disorder Patients Treated on Valproate or Lithium and in Need of Further Clinical Improvement

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)

Secondary outcome:

Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)

Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)

Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set)

Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)

Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)

Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)

Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set)

Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)

Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)

Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)

Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Key inclusion criteria:

- Clinical diagnosis of bipolar I disorder mania, manic or mixed episode, with or

without psychotic features

- Current ongoing lithium or valproate treatment with the possibility of benefiting,

based on the investigator's clinical judgment, from adjunctive treatment with aripiprazole

- Therapeutic serum levels of lithium or valproate and a Young Mania Rating Total Score

of 16 or higher at screening and baseline

- Participants taking current lithium or valproate treatment combined with

antipsychotic medication other than aripiprazole are acceptable, provided that the other antipsychotic medication is washed out at least 3 days prior to the blood draw for therapeutic plasma levels of lithium and valproate determination. Long-acting antipsychotics must be washed out prior to entering the double-blind treatment. Key exclusion criteria:

- Women of childbearing potential who are unwilling or unable to use an acceptable

method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of investigational product

- A diagnosis of delirium, dementia, amnesia or other cognitive disorder, or a

psychotic disorder

- Current diagnosis of delirium, dementia, a cognitive disorder (ie, amnesia), or a

psychotic disorder (ie, schizophrenia or schizoaffective disorder)

- Current diagnosis of bipolar II disorder, bipolar disorder not otherwise specified,

or any other primary psychiatric disorder other than bipolar I disorder mania

- Thyroid pathology

- Demonstrated cocaine abuse or dependence within the past 3 months prior to screening.

- History of neuroleptic malignant syndrome from antipsychotic agents

- Manic symptoms that investigator considers refractory to treatment

- Previous nonresponsive (by investigator judgment) to aripiprazole for manic symptoms

- Significant risk of suicide based on history, mental status exam, or investigator

judgment.

Local Institution, Salzburg 5020, Austria

Local Institution, Wien 1090, Austria

Local Institution, Hradec Kralove 500 05, Czech Republic

Local Institution, Litomerice 41201, Czech Republic

Local Institution, Prague 2 120 00, Czech Republic

Local Institution, Praha 10 101 00, Czech Republic

Local Institution, Praha 160 00, Czech Republic

Local Institution, Beaupuy 31850, France

Local Institution, Brumath Cedex 67173, France

Local Institution, Chateau Gontier 53200, France

Local Institution, Clermont-Ferrand Cedex 63001, France

Local Institution, Dijon 21000, France

Local Institution, Dole 39100, France

Local Institution, Jonzac Cedex 175003, France

Local Institution, Le Vesinet 78110, France

Local Institution, Montpellier Cedex 5 34295, France

Local Institution, Nimes 30900, France

Local Institution, Paris 75116, France

Local Institution, Reims Cedex 51092, France

Local Institution, Saint Nazaire Cedex 44606, France

Local Institution, Sotteville Les Rouen 76300, France

Local Institution, Strasbourg Cedex 67091, France

Local Institution, Ellwangen 73479, Germany

Local Institution, Ostfildern 73760, Germany

Local Institution, Athens 151 26, Greece

Local Institution, Leros 85400, Greece

Local Institution, Nea Ionia-Athens 14233, Greece

Local Institution, Tripolis 22100, Greece

Local Institution, Budapest 1125, Hungary

Local Institution, Budapest 1097, Hungary

Local Institution, Budapest 1083, Hungary

Local Institution, Budapest 1135, Hungary

Local Institution, Gyor 9024, Hungary

Local Institution, Gyula 5700, Hungary

Local Institution, Campobasso 86100, Italy

Local Institution, Foggia 71100, Italy

Local Institution, Foligno (Pg) 06034, Italy

Local Institution, Genova 16132, Italy

Local Institution, La Spezia 19124, Italy

Local Institution, Milano 20121, Italy

Local Institution, Napoli 80131, Italy

Local Institution, Pisa 56126, Italy

Local Institution, Roma 00168, Italy

Local Institution, Roma 00189, Italy

Local Institution, Sant'Arsenio (Salerno) 84037, Italy

Local Institution, Choroszcz 16070, Poland

Local Institution, Gdansk 80-952, Poland

Local Institution, Krakow 30-393, Poland

Local Institution, Krakow 31-501, Poland

Local Institution, Poznan 60-572, Poland

Local Institution, Swiecie N/Wisla 86-100, Poland

Local Institution, Bucharest 041915, Romania

Local Institution, Cluj-Nappoca 400012, Romania

Local Institution, Iasi 700282, Romania

Local Institution, Khotkovo 141371, Russian Federation

Local Institution, Krasnodar 350087, Russian Federation

Local Institution, Moscow 119992, Russian Federation

Local Institution, Moscow 115522, Russian Federation

Local Institution, Rostov-On-Don 344010, Russian Federation

Local Institution, Samara 443016, Russian Federation

Local Institution, St.Petersburg 192019, Russian Federation

Local Institution, Tomsk 634014, Russian Federation

Local Institution, Barcelona 08036, Spain

Local Institution, Madrid 28046, Spain

Local Institution, Murcia 30120, Spain

Local Institution, Ankara 06100, Turkey

Local Institution, Antalya 07070, Turkey

Local Institution, Denizli 20100, Turkey

Local Institution, Johannesburg, Gauteng 2198, South Africa

Local Institution, Soweto, Gauteng 2001, South Africa

Local Institution, Vereeniging, Gauteng 1939, South Africa

Local Institution, Pinetown, Kwa Zulu Natal 3600, South Africa

Local Institution, Cape Town, Western Cape 7530, South Africa

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Starting date: June 2008
Last updated: November 7, 2013