Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study.

Abstract

BACKGROUND:

This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18-70 years) with schizophrenia, previously stabilized on PP1M.

METHODS:

After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase.

RESULTS:

Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected.

CONCLUSION:

Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia.

• Authors: Adam J Savitz, Haiyan Xu, Srihari Gopal, Isaac Nuamah, Paulien Ravenstijn, Adam Janik, Alain Schotte, David Hough, Wolfgang W Fleischhacker
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 19 Issue 7 (07 2016) ISSN: 1469-5111 [Electronic] England
• PMID: 26902950 (Publication Type: Clinical Trial, Phase III, Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of CINP.

Chemical References

• Antipsychotic Agents
• Delayed-Action Preparations
• Paliperidone Palmitate

Topics

• Adolescent
• Adult
• Aged
• Antipsychotic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Delayed-Action Preparations (adverse effects, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Injections, Intramuscular
• Male
• Middle Aged
• Paliperidone Palmitate (adverse effects, blood, pharmacokinetics, therapeutic use)
• Schizophrenia (blood, drug therapy)
• Secondary Prevention
• Time Factors
• Treatment Outcome
• Young Adult