The Efficacy and Safety of Risperidone in the Treatment of Adolescents With Schizophrenia

The Efficacy and Safety of Risperidone in Adolescents With Schizophrenia: a Comparison of Two Dose Ranges of Risperidone

A clinical study to compare the safety and effectiveness of two different dose ranges of risperidone solution in the treatment of adolescents with a diagnosis of schizophrenia.

This is a clinical study of an investigational drug called risperidone in the treatment of schizophrenia in adolescents. Initially children (age 2 to 12 yrs) and schizophreniform subjects were also allowed but excluded following protocol amendment. The study will include approximately 260 patients aged 13 to 17 years with a diagnosis of schizophrenia. Subjects will be randomly assigned to one of two groups on enrollment and will be given risperidone as an oral solution each day for 8 weeks at doses within one of two dose different ranges, according to the assigned study group. Initially the two dose range were 0.15-0.4 mg/day and 1.5-4mg/day but were changed in protocol amendment to evaluate the maximum tolerated dose with a minimum of 3.5mg/day and maximum of 6mg/day (resp. 0.35 and 0.6mg/day in low dose treatment arm) Risperidone lower dose (0.35-0.6 mg/day [subjects >=50kg] or 0.007-0.012 mg/kg/day [subjects <50 kg]) as 0.1 mg/mL oral solution or risperidone higher dose (3.5-6 mg/day [subjects >=50 kg] or 0.07-0.12 mg/kg/day [subjects <50 kg]) as 1 mg/mL oral solution for 8 weeks. Daily dose can be given all at once or through 2 administrations (in morning and evening); the dose is increased based on efficacy and tolerability.

Change in total PANSS (Positive and Negative Syndrome Scale for Schizophrenia) from baseline to the 8-week endpoint

Change from baseline in PANSS subscale scores and Clinical Global Impression (CGI-S and CGI-I) scores, number of subjects achieving a clinical response (at least 20% improvement in total PANSS), safety, tolerability and pharmacokinetics.

Inclusion Criteria: Subjects will be eligible for study enrollment if they: are adolescents between the ages of 13 and 17 years have a confirmed diagnosis of schizophrenia and are suffering from an acute episode provide their assent and parental informed consent to participate are otherwise relatively healthy on the basis of a medical and physical examination and are able to be in-patients for approximately 2 weeks. Exclusion Criteria: Subjects will be excluded from the study if they: meet the criteria for psychiatric disorders other than schizophrenia have moderate or severe mental retardation fail to respond to treatment with at least two typical or atypical antipsychotics have a history of substance dependence within the 3 months before screening are considered at risk for suicidal or violent behavior have a seizure disorder have a history of neuroleptic malignant syndrome, similar encephalopathic syndrome, or tardive dyskinesia or receive prohibited medication within a specified period before screening.

Haas M, Eerdekens M, Kushner S, Singer J, Augustyns I, Quiroz J, Pandina G, Kusumakar V. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study. Br J Psychiatry. 2009 Feb;194(2):158-64. doi: 10.1192/bjp.bp.107.046177.

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