A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.

Many patients with schizophrenia have difficulty adhering to a daily oral treatment regimen. Long-acting injectable formulations, such as long-acting injectable paliperidone palmitate, may provide therapeutic plasma concentrations over several weeks, thereby eliminating the need for daily oral medication and making compliance easier. This study is a randomized (patients will be assigned to different treatment groups based solely on chance), double-blind (neither the patient nor the physician will know if placebo or drug is being given and at what dose), placebo-controlled, parallel-group, multicenter study followed by an open-label extension period in patients with schizophrenia. The study is designed to evaluate the efficacy of paliperidone palmitate (a long-acting injectable formulation) in delaying the time to and decreasing the rate of recurrence compared with placebo in patients with schizophrenia. The study will consist of 5 periods: an up to 7-day screening/washout/tolerability period, a 9-week open-label transition period, a 24-week open-label maintenance period, a randomized, variable-length double-blind, placebo-controlled recurrence prevention period, and an up to 52-week open-label extension period. Patients will have intramuscular (i.m.) study drug injections and efficacy and safety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated during the study using a recurrence assessment, the Positive and Negative Symptom Scale for Schizophrenia (PANSS), the Clinical Global Impression - Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Safety will be assessed throughout the study by monitoring adverse events; use of extrapyramidal symptoms (EPS) rating scales (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Rating Scale [BARS], Simpson Angus Scale [SAS]); clinical laboratory testing; vital signs (temperature, blood pressure, and heart rate) measurements; electrocardiograms (ECGs); and physical examinations. Additionally, the patients will assess the tolerability of the injections by evaluating the pain of the injection and the pain at the injection sites. Tolerability test: 3 mg/day of oral ER OROS paliperidone for 4 days. Transition (9 wks): 50 mg eq. paliperidone palmitate i.m. dose on Day 1, then i.m. injections (25, 50, or 100 mg eq.) once every 4 wks (q4wk). Maintenance (24-wks): paliperidone palmitate i.m. injections (25, 50, or 100 mg eq.) q4wk. Recurrence Prevention: paliperidone palmitate i.m. injections (25, 50, or 100 mg eq. or placebo) q4wk. Open-label paliperidone palmitate (25, 50, 75, or 100 mg eq.) q4wk for 12 dosing periods.