Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

Abstract

Background: This double-blind, parallel6group, multicenter, phas-3 study was designed to test the noninferiority of paliperidone palmitate 36month formulation (PP3M) to the currently marketed 16month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤ 3 weeks) and a 176week, exible-dosed, open-label phase (PP1M: day 1 [150 mg eq. deltoid], day 8 [100 mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150 mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (xed-dose, 175, 263, 350, or 525 mg eq. deltoid/gluteal) or PP1M (xed-dose, 50, 75, 100, or 150 mg eq. deltoid/ gluteal) for a 486week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n = 504; PP1M: n = 512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n = 37, 8 %; PP1M: n = 45, 9%; difference in relapse-free rate: 1.2 % [95 % CI: 62.7 %; 5.1 %]) based on Kaplan-Meier estimates (primary efficasy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression- Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability pro les; increased weight was the most common treatment6emergent adverse event (double-blind phase; 21 % each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 36month dosing interval is a unique option for relapse prevention in schizophrenia.