Efficacy and safety of paliperidone palmitate 3-month versus 1-month formulation in patients with schizophrenia: comparison between European and non-European population

Abstract

Purpose

This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia.

Patients and methods

In this randomized, DB, parallel-group study, adult patients (18–70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4–12 weeks) phase. Patients were treated with fixed-dose PP3M (175–525 mg eq deltoid/gluteal) or PP1M (50–150 mg eq deltoid/gluteal) for 48 weeks in DB phase.

Results

In total, 487 European (PP3M, n=242; PP1M, n=245) and 508 non-European patients (PP3M, n=241; PP1M, n=267) entered DB phase (modified intent-to-treat (mITT) [DB] analysis set). Among the 508 non-European patients in mITT set, 67.7% were from Asia (n=344) and 32.3% were from rest of world (ROW, n=164). During the DB phase, similar percentage of Europeans (PP3M: 7%; PP1M: 8%) and non-Europeans (PP3M: 9%; PP1M: 10%) experienced relapse (Kaplan–Meier estimate PP3M–PP1M [95% CI] of percentage of relapse-free patients at the end of DB phase [primary endpoint]: European: 1.0% [−4.3%; 6.2%]; non-European: 1.4% [−4.4%; 7.1%]; Asian: 1.6% [−5.7%; 9.0%]; and ROW: 1.4% [−7.0%, 9.8%], per-protocol analysis set). Incidence of treatment-emergent adverse events (TEAEs) was lower in Europeans (PP3M: 56%, PP1M: 59%) than non-Europeans (PP3M: 80%, PP1M: 73%). The most commonly reported TEAE was weight gain.

Conclusion

PP3M showed similar efficacy to PP1M in Europeans and non-Europeans, consistent with non-inferiority of PP3M to PP1M observed in overall population. Rates of AEs were higher in non-Europeans. However, weight gain was greater in non-Europeans, especially the Asian population.

Keywords:

• long-acting injectable
• non-inferiority
• randomized
• relapse
• tolerability

Acknowledgments

Dr Shruti Shah and Dr Himabindu Gutha (both SIRO Clinpharm Pvt. Ltd) provided writing assistance and Dr Ellen Baum (Janssen Research & Development, LLC) provided additional editorial support for this manuscript. Authors thank Dr Wolfgang Fleischhacker for scientific advice. The authors also thank the study participants, without whom this study would never have been accomplished, and all the investigators for their participation in this study. Portions of this work were previously presented as a poster at ‘29th ECNP congress’, Vienna, Austria, September 17–20, 2016; DGPPN Congress, City Cube Berlin, Germany, November 23–26, 2016; Society of Biological Psychiatry (SOBP) 72nd Annual Scientific Convention, May 18–20, 2017, San Diego, California and poster abstract was published in European Neuropsychopharmacology; 26:S548–S549: DOI: https://doi.org/10.1016/S0924-977X(16)31592-9; and in Biological Psychiatry; 81:S211: DOI: https://doi.org/10.1016/j.biopsych.2017.02.1127.

Author contributions

Drs Savitz, Gopal, Hargarter, and Hough were involved in study design, data collection, analysis and interpretation. Drs Xu and Nuamah were responsible for the statistical analyses and design/interpretation of study results. Dr Ravenstijn was involved in pharmacokinetic analysis. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

All authors except for Dr Hargarter are employees of Janssen Research & Development; Dr Hargarter is a former employee of Janssen Cilag EMEA. All authors own stock in Johnson & Johnson the parent company of the Janssen companies. The authors report no other conflicts of interest in this work.