We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population.
*Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ; †Department of Psychiatry and Behavioral Sciences, Keck School of Medicine at the University of Southern California, Los Angeles, CA and ‡Republican Vilnius Psychiatric Hospital, Vilnius, Lithuania.
Received August 1, 2006; accepted after revision November 2, 2006.
Some of these data were submitted for presentations at Collegium Internationale Neuropsychopharmacologicum (USA) on July 2006 and European Congress of Neuropsychopharmacology (France) on September 2006.
This study is registered at ClinicalTrials.gov corresponding to NCT number NCT00086320. This study was funded by Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ.
Dr George Simpson has received research support and worked as a consultant for Janssen Pharma, LLC, USA, an operating company of Johnson & Johnson.
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