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. 2019 Feb 21:15:587-602.
doi: 10.2147/NDT.S189668. eCollection 2019.

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

Adam J Savitz  1 , Haiyan Xu  1 , Srihari Gopal  1 , Isaac Nuamah  1 , Paulien Ravenstijn  2 , David Hough  1 , Ludger Hargarter  3
Affiliations

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

Adam J Savitz et al. Neuropsychiatr Dis Treat. .

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.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Study design and disposition of patients from Europe, Asia and rest of the world (ITT [OL] analysis set and mITT [DB] analysis set). Notes: The follow-up visit was 4 weeks after the end-of-study visit for those patients who completed the DB phase without a relapse and 12 weeks for those who withdrew early or had a relapse during the DB phase. In OL phase, patients received PP1M on day 1 (150 mg eq deltoid), day 8 (100 mg eq deltoid), wherein flexible dosing was administered at weeks 5 and 9. PP1M: 50, 75, 100 or 150 mg eq dose; PP3M: 175, 263, 350, 525 mg eq dose (3.5 × PP1M dose). Abbreviations: DB, double-blind; EU, Europe; OL, open-label; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; ROW, rest of the world.
Figure 2
Figure 2
Time-to-relapse during the double-blind phase and percentage of patients that remained relapse-free: (A) European patients; (B) Asian patients; (C) rest of the world patients (per-protocol analysis set). Notes: Based on Kaplan–Meier product limit estimates; per-protocol analysis set defined as patients who were randomly assigned to treatment during the DB phase and received at least 1 dose of DB study drug. Patients did not have any major protocol violations that could impact the efficacy such as violations of eligibility criteria for patient enrollment and randomization, errors in treatment assignment or use of excluded medications. Abbreviations: DB, double-blind; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month.
Figure 2
Figure 2
Time-to-relapse during the double-blind phase and percentage of patients that remained relapse-free: (A) European patients; (B) Asian patients; (C) rest of the world patients (per-protocol analysis set). Notes: Based on Kaplan–Meier product limit estimates; per-protocol analysis set defined as patients who were randomly assigned to treatment during the DB phase and received at least 1 dose of DB study drug. Patients did not have any major protocol violations that could impact the efficacy such as violations of eligibility criteria for patient enrollment and randomization, errors in treatment assignment or use of excluded medications. Abbreviations: DB, double-blind; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month.
Figure 3
Figure 3
Mean (SE) total PANSS score (LOCF) over time: (A) European patients; (B) non-European patients (mITT [DB] analysis set). Abbreviations: DB, double-blind; OL, open-label; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; PANSS, Positive and Negative Syndrome Scale.
Figure 3
Figure 3
Mean (SE) total PANSS score (LOCF) over time: (A) European patients; (B) non-European patients (mITT [DB] analysis set). Abbreviations: DB, double-blind; OL, open-label; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; PANSS, Positive and Negative Syndrome Scale.
Figure 4
Figure 4
Percentage of European patients with (A) symptomatic remission; (B) symptomatic and functional remission over time during the double-blind phase (mITT [DB] analysis set). Abbreviations: PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; DB, double-blind.
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References

    1. Bhanji NH, Chouinard G, Margolese HC. A review of compliance, depot intramuscular antipsychotics and the new long-acting injectable atypical antipsychotic risperidone in schizophrenia. Eur Neuropsychopharmacol. 2004;14(2):87–92. - PubMed
    1. Lieberman JA, Stroup TS, Mcevoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–1223. - PubMed
    1. Valenstein M, Ganoczy D, Mccarthy JF, Myra Kim H, Lee TA, Blow FC. Antipsychotic adherence over time among patients receiving treatment for schizophrenia: a retrospective review. J Clin Psychiatry. 2006;67(10):1542–1550. - PubMed
    1. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. PS. 2004;55(8):886–891. - PubMed
    1. Doering S, Müller E, Köpcke W, et al. Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder. Schizophr Bull. 1998;24(1):87–98. - PubMed