A Study of the Safety and Efficacy of Injectable Risperidone in the Prevention of Bipolar Mood Episodes

Study Overview
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Brief Summary
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The purpose of this study is to determine if risperidone is effective and safe in the prevention of mood episodes in patients with bipolar 1 disorder.

Detailed Description
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RISPERDAL CONSTA (risperidone long-acting injection) may provide substantial improvement, by reducing patient non-compliance, in the long-term treatment of bipolar I disorder. This is a randomized (patients are assigned different treatments based on chance), double-blind, (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage) placebo-controlled study to explore the safety and effectiveness of RISPERDAL CONSTA in the prevention of mood episodes in patients with bipolar 1 disorder. This study includes 5 periods: a screening period lasting up to 1 week; an open-label RISPERDAL (oral risperidone) treatment period lasting 3 weeks; an open-label RISPERDAL CONSTA stabilization period lasting 26 weeks; a double-blind period lasting up to 24 months; and an open-label extension with RISPERDAL CONSTA lasting 8 weeks. Efficacy will be assessed using the Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions - Severity (CGI-S) scale, Medical Outcomes Study Short Form 36 (SF-36), and the Personal and Social Performance (PSP) scale. Safety will be evaluated throughout the study and includes assessment of adverse events, clinical laboratory tests (including hematology, serum chemistry, blood glucose/lipid profile, prolactin, and urinalysis); electrocardiograms (ECGs), vital signs (pulse and blood pressure), physical examination, body mass index (BMI), and the Extrapyramidal Symptom Rating Scale (ESRS). Oral risperidone (flexible dosage) 1 to 6 mg/day for the first 3 weeks. Risperidone LAI i.m. injections (12.5mg, 25 mg, 37.5 mg, or 50 mg) given every 2 weeks for up to approximately 2.6 years (only 6 months for patients receiving placebo during DB-period)

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Explore the Efficacy and Safety of Risperidone Long-acting Intramuscular Injectable in the Prevention of Mood Episodes in Bipolar 1 Disorder, With Open-label Extension

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Risperdal Consta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of bipolar 1 disorder, currently experiencing a mixed or manic episode or stable Two or more bipolar mood episodes in the last 2 years excluding current episode Negative pregnancy test Exclusion Criteria: History of > than 4 mood episodes a year during the last two years patients experiencing a depressive episode History of antisocial or borderline personality illness Has unstable or serious general medical illness Has received medications disallowed by study criteria.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Risperdal Consta 12.5 25 37.5 or 50mg intramuscular (IM) injection every 2 weeks | Drug: Risperdal Consta<br>* 12.5, 25, 37.5 or 50mg intramuscular (IM) injection every 2 weeks<br>|
| Placebo Comparator: 002<br>Placebo Matching placebo intramuscular (IM) injection every 2 weeks | Drug: Placebo<br>* Matching placebo intramuscular (IM) injection every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had a Mood Relapse. | Mood Relapse was defined as: The subject met DSM-IV criteria for a manic, hypomanic, mixed, or depressive episode; or, the subject needed treatment intervention with any mood stabilizer, antipsychotic medication (other than study drug), benzodiazepine (beyond the dosage allowed), or antidepressant medication; or the subject required hospitalization for any bipolar mood episode; or the subject had a YMRS or MADRS score >12 or a CGI-S score >4; or a dose increase, or supplementation with oral risperidone or another antipsychotic or mood stabilizer, was needed in the opinion of the investigator. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Young Mania Rating Scale (YMRS) Scores. | Measure of mania; score range 0 to 60 (lower score = less severity) | Baseline and Endpoint (last observation carried forward) of 24 month Double-Blind Period IV | 
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) | Measure of depression; score range 0 to 60 (lower score = less severity) | Baseline and Endpoint (last observation carried forward) of 24 month Double-Blind Period IV | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood episodes, Bipolar 1 disorder, Intramuscular Injectable, risperidone, safety and efficacy