A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group-comparison Trial of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode

Study Overview
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Brief Summary
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The primary objective of this trial is to evaluate the clinical efficacy and safety of aripiprazole in comparison to placebo in patients with Bipolar I Disorder experiencing a manic or mixed episode.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group-Comparison Trial of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trial subjects will be men and women of age 18 or above and below the age of 65 who will not be turning 65 during the trial. Patients have the ability to understand and to provide informed consent to the examination, observation, and evaluation processes specified in this protocol, and have signed the informed consent form based on a full understanding of the trial. Patients who meet DSM-IV-TR criteria for manic or mixed episodes and have been diagnosed as having 296.4x Bipolar I Disorder in which the most recent episode was manic or 296.6x Bipolar I Disorder in which the most recent episode was mixed Patients with a YMRS total score of 20 or more Exclusion Criteria: Patients presenting with a clinical picture and/or history that is consistent with a DSM-IV-TR diagnosis of: Delirium, dementia, amnestic disorder, or other cognitive disorders Schizophrenia or other psychotic disorder Personality disorder Patients experiencing their first manic or mixed episode Patients whose current manic episode has lasted for more than 4 weeks Patients with psychotic symptoms that are clearly due to another general medical condition or direct physiological effects of a substance Patients who have met DSM-IV-TR criteria for a substance-related disorder within 3 months (90 days) prior to informed consent (excluding caffeine- and nicotine-related disorders, but including abuse of benzodiazepines) Patients who have received ECT treatment within 8 weeks prior to informed consent Patients who are expected to require administration of ultrashort-acting or short-acting benzodiazepine receptor agonist hypnotics and antianxiety drugs (See (1) of 4.2.2) at doses exceeding the equivalent of 15 mg/day of diazepam (Only for those patients using such drugs) Patients at significant risk of developing a severe adverse event. Patients who have a medical condition that would interfere with assessments of safety or efficacy during the course of the trial, or who have a history of such a condition. Patients who have received any of the following treatments during the screening period: Reserpine Levodopa, dopamine receptor stimulants Monoamine oxidase inhibitors Psychostimulants Thyroid hormones, antithyroid drugs Corticosteroids (other than topical preparations) Adrenaline All other investigational or unapproved agents ECT Light therapy For patients who take lithium, valproate, or carbamazepine within 3 days prior to commencement of investigational product administration, those patients with serum concentrations of lithium greater than 0.6 mmol/L, serum concentrations of valproate greater than 50 µg/mL, or serum concentrations of carbamazepine greater than 4 µg/mL Patients judged to have a diabetic blood glucose level (judgment based on use of a self-monitoring blood glucose meter permissible), or patients whose HbA1c is 6.5% or higher Patients with a history or a complication of diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Aripiprazole<br>* oral, 24mg/day<br>* Other names: OPC-14597;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* oral, 0mg(4tablets)/day<br>* Other names: OPC-14597;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Young Mania Rating Scale (YMRS) | Using LOCF datasets, change in YMRS total score from baseline (Day 1) to endpoint (Day 21) was evaluated through analysis of covariance(ANCOVA). YMRS is composed of 11 evaluation items with 5 rating levels each. Items rated on a scale of 0 to 4 (comprising 5 rating levels of one point each) are 1) elevated mood, 2) increased motor activity/energy, 3) sexual interest, 4) sleep, 7) language-thought disorder, 10) appearance, and 11) insight. Items rated on a scale of 0 to 8 (comprising 5 rating levels of two points each) are 5) irritability, 6) speech (rate and amount), 8) content, and 9) disruptive-aggressive behavior. YMRS ranges from 0 (best possible outcome) to 60 (worst possible outcome). | Day1, Day21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Bipolar Version (CGI-BP), Severity of Illness Score (Mania) | CGI-BP severity of illness is a scale for overall evaluation of the severity of bipolar disorder; it comprises 3 components-mania, depression, and overall bipolar illness. CGI-BP severity of illness score (mania) ranges form 1 (normal, not ill) to 7 (very severely ill). Using LOCF datasets, change in CGI-BP severity of illness score (mania) from baseline (Day 1) to endpoint (Day 21) was evaluated through ANCOVA. | Day1, Day21 |