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

Otsuka

Status and phase: Completed; Phase 3

Conditions: Bipolar Disorder Mania

Treatments: Drug: Lithium; Drug: Valproate; Drug: Aripiprazole; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00665366

CN138-502

EudraCT number 2007-005959-42

Details and patient eligibility

About

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.

Enrollment: 493 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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493 participants in 2 patient groups, including a placebo group

Placebo + valproate or lithium

Placebo Comparator group

Description:

Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.

Treatment:

Drug: Placebo

Drug: Lithium

Drug: Valproate

Aripiprazole + valproate or lithium

Active Comparator group

Description:

Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.

Treatment:

Drug: Aripiprazole

Drug: Lithium

Drug: Valproate