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, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M.Methods:After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week 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:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). 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 profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected.Conclusion:Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia.

Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate

“…[19] Prescription guidelines for PP3M recommend the following dose conversion from the last dose of PP1M to the first dose of PP3M (PP1M dose → PP3M dose): 78 mg → 273 mg, 117 mg → 410 mg, 156 mg → 546 mg, or 234 mg → 819 mg. Prior to FDA approval in 2015, the safety and efficacy of PP3M were demonstrated in two double-blind, randomized clinical trials [20,21]. While patients' characteristics and treatment patterns during the period prior to PP3M initiation have been assessed [22], there is a need to assess the impact of transitioning to PP3M on treatment adherence, healthcare resource utilization (HRU), and costs.…”

Pharmacological Treatment of Schizophrenia:

“…A double-blind RCT showed superiority of 3-month paliperidone palmitate over placebo for delaying time to relapse of symptoms (hazard ratio = 3.81) [57]. The 3 month formulation was also compared to monthly paliperidone palmitate in a non-inferiority study demonstrating a comparably low relapse risk in both groups [58]. Adverse event profiles of the two formulations were similar especially also with respect to injection side complications.…”

Novel Treatment Options in Depression and Psychosis

“…The new paliperidone LAI with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. 34 LAI antipsychotics eliminate the need for daily dosing, typically ensure sustained plasma levels for several weeks, and help to reliably monitor adherence. The new LAI options provide additional flexibility in terms of increasing the time between injections.…”