Efficacy and Safety of Paliperidone Palmitate 6-Month versus Paliperidone Palmitate 3-Month Long-Acting Injectable in European Patients with Schizophrenia: A Post Hoc Analysis of a Global Phase-3 Double-Blind Randomized Non-Inferiority Study

Abstract

Purpose To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M). Methods This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan–Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as −10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated. Results A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of −4.9% (95% CI: −9.2%, −0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs. Conclusion The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.

Three-Year Outcomes of 6-Month Paliperidone Palmitate in Adults With Schizophrenia

“…Although the definition of functional recovery is complex, recent studies have stressed the importance of factors influencing life engagement and quality of life, such as cognition, personal autonomy, professional activity, social relationships or support, and environmental factors . The longer dosing intervals associated with LAI antipsychotics contribute to clinical stability, providing potential for long-term improvements in functionality, social integration, and patient empowerment . Furthermore, LAI antipsychotic treatment in combination with nonpsychopharmacologic treatment strategies may encourage personal recovery beyond the framework of traditional outcome measures and mental health services.…”

“… 32 , 33 , 34 , 35 The longer dosing intervals associated with LAI antipsychotics contribute to clinical stability, providing potential for long-term improvements in functionality, social integration, and patient empowerment. 36 , 37 Furthermore, LAI antipsychotic treatment in combination with nonpsychopharmacologic treatment strategies may encourage personal recovery beyond the framework of traditional outcome measures and mental health services.…”