Time to onset and time to resolution of extrapyramidal symptoms in patients with exacerbated schizophrenia treated with 3-monthly vs once-monthly paliperidone palmitate
Received 25 May 2018
Accepted for publication 15 August 2018
Published 25 October 2018 Volume 2018:14 Pages 2807—2816
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Justinn Cochran
Peer reviewer comments 3
Editor who approved publication: Dr Roger Pinder
Maju Mathews,1 Isaac Nuamah,1 Adam J Savitz,1 David W Hough,1 Dean Najarian,2 Edward Kim,2 Srihari Gopal1
1Janssen Research and Development, LLC, Titusville, NJ, USA; 2Janssen Scientific Affairs, Titusville, LLC, NJ, USA
Objective: The aim of this study was to evaluate the safety of 3-monthly paliperidone palmitate (PP3M) vs once-monthly paliperidone palmitate (PP1M) treatment with regard to extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) in patients with schizophrenia, previously stabilized on PP1M treatment.
Patients and methods: Data on overall incidence, time to onset (TTO), and time to resolution (TTR) of EPS-related TEAEs (overall, subclasses such as dyskinesia, dystonia, hyperkinesia, parkinsonism, and tremor) from a randomized double-blind (DB) non-inferiority study were compared between PP3M and PP1M. Subgroup analysis was performed by age (18–25, 26–50, and 50+ years) and final open-label (OL) dose (50/75, 100, and 150 mg eq.).
Results: Overall incidence of spontaneously reported EPS-related TEAEs decreased from 12.6% (PP1M) in OL phase to 8.3% (PP3M) and 7.4% (PP1M) in the DB phase; overall median TTO and TTR values were comparable between both groups. Among patients with reported EPS-related TEAEs, the median TTO for all EPS-related TEAEs was 17 days (PP1M) in OL phase and 115 days (PP3M) and 98.5 days (PP1M) in DB phase; median TTR was 36.5 days (PP1M) in OL phase and 91 days (PP3M) and 85.5 days (PP1M) in DB phase. No clear dose- or age-related differences in TTO and TTR of EPS-related TEAEs were noted.
Conclusion: Despite differences in apparent half-life and pharmacokinetic profiles (peak plasma exposure of PP3M formulation is 70% higher than that of PP1M formulation), both PP3M and PP1M formulations exhibited comparable incidence of EPS-related TEAEs, TTO, and TTR in patients with schizophrenia.
Keywords: extrapyramidal symptoms, once-monthly paliperidone palmitate, 3-monthly paliperidone palmitate, time to onset, time to resolution
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