A Phase 3 Non-Inferiority Study Comparing Paliperidone Palmitate 1-Month vs 3-Month Long-Acting Injectables for Negative Symptom Improvement in Schizophrenia

Background: Negative symptoms of schizophrenia are predictors of long-term disability. Paliperidone palmitate 3-month formulation (PP3M) provides a sustained release of paliperidone, permitting extended dosing interval of only 4 doses per year in patients with schizophrenia. Improvement in negative symptoms following PP3M and paliperidone palmitate 1-month formulation (PP1M) treatment was analyzed in this post hoc analysis.

Methods: Data from a double-blind (DB), phase-3 study in patients with schizophrenia (DSM-IV-TR) were analyzed. After screening (3 weeks), patients entered 17-week open-label (OL) phase to receive flexibly-dosed PP1M followed by 48-week DB phase to receive PP1M or PP3M. Positive and Negative Syndrome Scale scores (PANSS) for PP1M vs PP3M were assessed.

Results: Of the 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, the mean (SE) negative subscale total was 23.2 (0.12), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (23.2 [4.60] and 22.3 [4.87]) and DB (15.9 [4.99] and 14.9 [4.81]) phases, both R2: 0.16. PANSS negative subscale score changes from DB baseline for PP1M vs PP3M were similar over time (mean (SD):-1.4 [3.67], R2: 0.06 vs -1.4 [3.63], R2: 0.05).

Conclusion: PP3M and PP1M demonstrated consistent efficacy in patients with moderate-to-severe negative symptoms of schizophrenia, including impact on patients with predominantly negative symptoms. Longer continuous treatment with PP3M showed greater benefit indicating that long-acting therapies are associated with improvement in negative symptoms over time. PP3M treatment for more than a year was associated with maximum improvements in negative symptoms.