A Study of the Efficacy and Safety of Long-acting Injectable Risperidone and Risperidone Tablets in Patients With Schizophrenia

A Parallel-Group Comparative Open-Label Study of Long-Acting Injectible Risperidone Versus Risperidone Tablets in Patients With Schizophrenia.

The purpose of this study is to evaluate the effectiveness and safety of risperidone, formulated as a long-acting injectable drug, compared with risperidone tablets in the treatment of patients with schizophrenia.

Although many schizophrenia patients currently take oral antipsychotic medications, it is estimated that up to 75% of them have difficulty adhering to the daily oral regimen. Long-acting injectable formulations may eliminate the need for daily medication and enhance patient compliance with the treatment regimen. This is an open-label, randomized, Phase III trial in patients with schizophrenia. One treatment group receives 25 to 50 mgs of long-acting risperidone, formulated for intramuscular injections, at study initiation and again after 2 weeks, while phasing out any previous antipsychotic medication during the initial 3 weeks of the study. Continuing in the treatment phase, long-acting injections are administered once every 2 weeks through Week 24, and post-treatment observation is performed for 6 weeks (total study duration of 30 weeks). Patients in the other treatment group take oral risperidone tablets, 2 to 6 mgs daily, from study initiation for 24 weeks. Post-treatment observation continues for 1 week for this group (total study duration of 25 weeks). Assessments of effectiveness made at specified intervals during treatment include Positive And Negative Syndrome Scale (PANSS), a scale for the measurement of symptoms of schizophrenia; Clinical Global Impression - Severity (CGI-S), a measure of overall severity of illness, and Clinical Global Impression - Changes (CGI-C); as well as, Brief Psychiatric Rating Scale (BPRS). Safety evaluations include the incidence of adverse events throughout the study; inspection of the injection site at times of treatment; Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), vital signs (pulse, blood pressure, temperature), and laboratory tests (hematology, biochemistry, urinalysis) at monthly intervals. The study hypothesis is that treatment with long-acting risperidone injections is not inferior to oral risperidone, as measured by changes in PANSS total score from baseline through endpoint (24 weeks), in patients with schizophrenia and is generally well-tolerated. Risperidone, long-acting formulation for intramuscular injections (25 milligrams[mg] to 50mg, maximum), given biweekly through 24 weeks. Oral risperidone (2mg/day to 6mg/day [maximum]) administered daily for 24 weeks.

Inclusion Criteria:

• Diagnosis of schizophrenia by the criteria of Diagnostic and Statistical Manual of Mental Diseases, 4th Edition (DSM-IV )
• treatment with an antipsychotic drug (up to 6 milligrams/day of risperidone or equivalent dose) for 28 days before study initiation with no change in the dosage
• Total Positive and Negative Syndrome Scale (PANSS) score >=60 and <120 at start of study.

Exclusion Criteria:

• Diagnosis of mental disease other than schizophrenia
• treated with a sustained-release injection of other antipsychotic medications within 60 days before the initiation of the study
• history of cerebrovascular accident, convulsive disorder such as epilepsy, diabetes mellitus, liver disease, kidney disease, cardiovascular disorder, malignancy or physical exhaustion due to dehydration or malnutrition
• have risk factors of diabetes mellitus, such as hyperglycemia.