A Randomized, Double-Blind, Multicenter, Noninferiority Study Comparing Paliperidone Palmitate 6-Month Versus the 3-Month Long-Acting Injectable in Patients With Schizophrenia

Dean Najarian, Panna Sanga, Steven Wang, Pilar Lim, Arun Singh, Mary Jane Robertson, Kristin Cohen, Alain Schotte, Ruth Milz, Raja Venkatasubramanian, Huybrecht T'Jollyn, David P Walling, Silvana Galderisi, Srihari Gopal, Dean Najarian, Panna Sanga, Steven Wang, Pilar Lim, Arun Singh, Mary Jane Robertson, Kristin Cohen, Alain Schotte, Ruth Milz, Raja Venkatasubramanian, Huybrecht T'Jollyn, David P Walling, Silvana Galderisi, Srihari Gopal

Abstract

Background: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia.

Methods: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen.

Results: Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M - PP3M) in the percentages of patients who remained relapse free was -2.9% (-6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of -10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged.

Conclusions: The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M.

Trial registration: Clinical Trials.gov identifier: NCT03345342.

Keywords: Paliperidone palmitate 3-month; paliperidone palmitate 6-month; relapse-free; schizophrenia.

© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.

Figures

Figure 1.
Figure 1.
Study design and patient disposition. Abbreviations: DB, double-blind; OL, open label; PP1M, paliperidone palmitate once-monthly formulation; PP3M, paliperidone palmitate 3-month formulation; PP6M, paliperidone palmitate 6-month formulation. aPatients in PP6M group received 2 placebo injections. bBefore pre-randomization (approximately one-half of the total maintenance phase sample was treated with PP3M) criteria are met. cAfter pre-randomization criteria are met. dOne patient entered the OL transition phase, withdrew, then re-screened again and entered the DB phase. eAmong 838 patients who entered the OL phase, 71 withdrew during OL transition phase and 767 entered the OL maintenance phase.
Figure 2.
Figure 2.
Semi-logarithmic mean (SD) plasma concentration time profiles of paliperidone after administration of PP3M at 350 or 525 mg eq. and PP6M at 700 or 1000 mg eq. (PK data analysis set) in the DB phase. The x-axis displays the day relative to the day of dosing (day 1) in the DB phase. Abbreviations: DB, double-blind; PK, pharmacokinetics; PP3M, paliperidone palmitate 3-month formulation; PP6M, paliperidone palmitate 6-month formulation.
Figure 3.
Figure 3.
Kaplan-Meier plot and 95% pointwise confidence-based percentage of patients without relapse during the DB phase (ITT-DB analysis set). Abbreviations: DB, double-blind; ITT, intent-to-treat; PP3M, paliperidone palmitate 3-month formulation; PP6M, paliperidone palmitate 6-month formulation.
Figure 4.
Figure 4.
Median prolactin level over time (safety analysis set). (A) Women (B) Men. Abbreviations: DB, double-blind; OL, open label; PP1M, paliperidone palmitate once-monthly formulation; PP3M, paliperidone palmitate 3-monthly formulation; PP6M, paliperidone palmitate 6-monthly formulation.

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Source: PubMed

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