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Phase 3 N=370 Randomized Double-blind Treatment

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

Bipolar Disorder Mania

Enrolled (actual)
370
Serious AEs
7.6%
Results posted
Feb 2013
Primary outcome: Primary: Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set) — -11.54; -13.57 Units on a scale — p=0.058

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Aripiprazole (Drug); Placebo (Drug); Lithium (Drug); Valproate (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Primary completion
Oct 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)
-11.54; -13.57 0.058
SECONDARY
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
-0.97; -0.93; -1.35; -1.46; -1.55; -1.83 0.669
SECONDARY
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
-0.01; -0.09; -0.02; -0.01; -0.04; 0.11 0.240
SECONDARY
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set)
-1.51; -1.59 0.567
SECONDARY
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
-5.68; -5.00; -8.59; -6.93; -9.18; -7.71 0.566
SECONDARY
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
26.2; 29.3; 46.2; 49.4; 53.8; 64.2 0.466
SECONDARY
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
30.6; 31.0; 48.9; 51.7; 57.0; 65.9 0.909
SECONDARY
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)
-2.13; -1.45; -3.20; -2.37; -2.30; -1.69 0.031 sig
SECONDARY
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
2.94; 2.99; 2.39; 2.64; 2.02; 2.24 0.197
SECONDARY
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
-0.06; 0.14; -0.02; 0.29; 0.07; -0.01 0.983
SECONDARY
Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)
4.3; 5.2; 2.7; 4.0
SECONDARY
Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set)
0.0; 0.0 0.582

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.

Eligibility 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00665366). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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