Primary Outcome Measures:
- To explore the pharmacokinetics of a 4-week LAI formulation of risperidone after single i.m. injection of 75 mg in the gluteal muscle.
Secondary Outcome Measures:
- To evaluate the safety and tolerability of a 4-week LAI formulation of risperidone after single i.m. injection of 75 mg in the gluteal muscle
An intramuscular (i.m.) injectable formulation of risperidone long-acting formulation is under development with the aim to provide a sustained and stable level of risperidone during each treatment cycle given every 4 weeks in patients with chronic stable schizophrenia. As this formulation is a long acting formulation, subjects will be treated with a 1 mg immediate release formulation in the first week to confirm that the subject does not develop an allergic reaction to the long acting formulation. Each subject recieves a total of two injections. The first one is the immediate release formulation and the second one the new long acting formulation. Eligible subjects can stay on their previous oral medication, no tapering of drugs is needed. Whole blood samples will be collected for the determination of risperidone and 9-hydroxy-risperidone concentrations in plasma. Whole blood samples will be obtained by venipuncture (needle stick) immediately before (pre-dose) and at 5, 10, 20, 30, 45 min, 1, 1.5, 2, 4, 6, 8,12, 16, 24, 36, 48, 72, 96 hours after the 1st injection and at 2, 6, 12, 24, 48, 96 hrs, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 39, 43, 50, 57, 64, 71, 78, 85 days after the 2nd injection of risperidone. Safety will assessed at limited visits throughout the study by monitoring scores of the Clinical Global Impression - Severity (using CGI-S, a scale used by a clinician to rate the severity of the patient's illness); adverse events; changes in clinical laboratory results; extrapyramidal symptoms (ie. neurological side effects of antipsychotic medications) will be evaluated using the Extrapyramidal Symptom Rating Scale (ESRS); physical examinations; electrocardiograms (ECGs); and patient + investigator evaluation of the injection site.
The study has two periods. In the first period all patients will receive one injection of 1 mg risperidone IR (immediate release) solution (liquid). The follow-up duration is 96 hours. In the second period, patients will receive one injection of risperidone 4-week formulation of 75 mg. The follow-up duration is 85 days. The injections in Period 1 and Period 2 will be given in the buttocks muscle (upper, outer side near the hip), separated by a 7 to 14 day wash-out period.