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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Bipolar Disorder Mania
- Sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Enrollment
- 493
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo + valproate or lithium
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
Intervention: Placebo
Placebo + valproate or lithium
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
Intervention: Lithium
Placebo + valproate or lithium
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
Intervention: Valproate
Aripiprazole + valproate or lithium
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.
Intervention: Aripiprazole
Aripiprazole + valproate or lithium
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.
Intervention: Lithium
Aripiprazole + valproate or lithium
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.
Intervention: Valproate
Outcomes
Primary Outcomes
Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)
Time Frame: Baseline to Week 12
The YMRS is a clinician-administered scale, consisting of 11 multiple choice items, and used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-though disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
Secondary Outcomes
- Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- 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)(Baseline to Weeks 6 and 12)
- Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set)(Baseline to Week 12)
- Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)(Baseline to Weeks 3,6, 9, and 12)
- Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)(Baseline to Weeks 3, 6, 9, and 12)
- Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)(Baseline to Weeks 3, 6, 9, and12)
- Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set)(Baseline to Week 12)