A Study to Evaluate the Safety and Effectiveness of Topiramate Compared to Placebo in the Treatment of Patients With Bipolar I Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of topiramate in adolescents with manic or mixed episodes of Bipolar I Disorder.

Detailed Description
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This is a 4-week study to evaluate the safety and effectiveness of topiramate compared to placebo in the treatment of Bipolar I Disorder with an optional 6-month open-label (OL) extension for qualified patients following completion of the study. On Days 1-28 patients will receive placebo or topiramate 2x/day by mouth except for the 1st and last doses which will be a single evening dose and a single morning dose, respectively. Study drug will be titrated in 100-mg increments to 400 mg/day and patients maintained on a stable dose through Day 28. During the OL extension phase, topiramate will be titrated over 5 days to 200 mg/day. After Day 7, topiramate may be tapered down to 100 mg/day or up to 600 mg/day, as clinically indicated.

Official Title
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A Randomized, Double-Blind, Multicenter, Placebo-Controlled 4-Week Study of the Safety and Efficacy of Topiramate in Adolescents With Acute Manic or Mixed Episodes of Bipolar I Disorder, With an Optional 6-Month Open-Label Extension

Conditions
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Bipolar Disorder, Affective Disorders, Psychotic, Mood Disorders, Mental Disorders

Intervention / Treatment
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* Drug: Topiramate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV diagnosis of Bipolar I Disorder (confirmed by the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version [K-SADS-P/L]) YMRS score greater than or equal to 20 General good health as determined by medical history, physical examination, and laboratory evaluations Ability to swallow tablets Patient's parent or guardian must be fully capable of monitoring the patient's disease process and compliance to treatment Parent(s) or legal guardian(s) must read and sign the informed consent form after the nature of the study has been fully explained and assent must be obtained from patients Exclusion Criteria: DSM-IV Axis I disorder diagnoses of autistic disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders not otherwise specified (NOS) DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within the 3 months prior to baseline. Acute or intermittent substance abuse prior to screening will not be exclusionary, depending upon the clinical judgment of the investigator Chronic antidepressant treatment within 4 weeks of randomization (5 weeks for fluoxetine), use of psychostimulants in the 7 days prior to baseline, use of any other psychotropic medications within 3 days or 5 half-lives, whichever is less, prior to baseline, or requirement for treatment with other psychotropic drugs on an ongoing basis Weight less than 33 kg or current or past history of anorexia nervosa Serious or unstable medical or neurological conditions

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 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: 001<br>Topiramate Double-blind period: Up to 400 mg/day (two 100-mg tablets twice a day) for 28 days. OL period: Up to 600 mg/day (three 100-mg tablets twice a day) for at least 6 months. | Drug: Topiramate<br>* Double-blind period: Up to 400 mg/day (two 100-mg tablets twice a day) for 28 days. OL period: Up to 600 mg/day (three 100-mg tablets twice a day) for at least 6 months.<br>|
| Placebo Comparator: 002<br>Placebo Double-blind period: Equal number of matching placebo tablets for each of the topiramate tablet strengths twice a day for 28 days. | Drug: Placebo<br>* Double-blind period: Equal number of matching placebo tablets for each of the topiramate tablet strengths twice a day for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in total Young Mania Rating Scale (YMRS) score |  | Baseline to Day 28 (or last available observation prior to Day 28). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Clinical Global Impression Scale (CGI-S) score |  | Baseline to Day 28 (or last available observation prior to Day 28). | 
| Change from baseline in Children's Global Assessment Scale (C-GAS) score |  | Baseline to Day 28 (or last available observation prior to Day 28). | 
| The number of patients continuing to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for manic or mixed episodes of Bipolar I Disorder |  | Day 28 (or last available observation prior to Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar, Mania, Pediatric, Children, Adolescent, Topiramate, Anticonvulsants, Central Nervous System Agents, Protective Agents, Neuroprotectiive Agents