Abstract
Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p⩽0.006) and PANSS negative and positive symptom Marder factor scores (p⩽0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.
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Acknowledgements
We thank Robert Rhodes, PhD, and the editorial staff of Clinical Connexion for writing and editorial support during the development of this paper, and Wendy P Battisti, PhD (Johnson & Johnson Pharmaceutical Research & Development, LLC) for additional writing, editorial, and scientific support. We also thank the following investigators for their participation in this study: Bulgaria: Grozeva, Penka, MD, Jivkov, Lubomir, MD, and Sayan, Loris, MD; Romania: Gabos Grecu, Losif, MD, Grigoriu, Alexandru Loan, MD, Popescu, Ioana, MD, and Teodorescu, Radu, MD; Russia: Andreev, Boris, MD, PhD, Ivanov, Mikhail, MD, PhD, Morozova, Margarita, MD, PhD, Panteleyeva, Galina, MD, PhD, Popov, Mikhail, MD, PhD, Reshetko, Olga, MD, PhD, Smulevich, Anatoly, MD, PhD, Suchkov, Yuri, MD, and Yakhin, Kausar, MD, PhD; South Africa: Ramjee, Paresh, MD and Selemani, S, MD; United States of America: Alam, Mohammed, MD, Askins, Howard, MD, Booker, J Gary, MD, Brenner, Ronald, MD, Buckley, Peter F, MD, Cuervo, Mario, MD, Dempsey, G Michael, MD, DeSilva, Himasiri, MD, Isacescu, Valentin, MD, Knapp, Richard D, DO, Larson, Gunnar L, MD, CCRI, Litman, Robert E, MD, Lowy, Adam F, MD, Marks, David M, MD, Nasrallah, Henry, MD, Riesenberg, Robert A, MD, Sack, David, MD, Shanbhag, Suhas, MD, Shiwach, Rajinder, MD, Valencerina, Madeleine M, MD, and Vijapura, Amit, MD.
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This study was funded by Johnson & Johnson Research & Development, LLC, Raritan, NJ, who was responsible for study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. Dr Nasrallah was an investigator in this study and over the past 3 years has received research grant support from Johnson & Johnson Pharmaceutical Research & Development to conduct FDA studies and investigator-initiated studies, and has received consultation fees and speaker honoraria as well. He has also received grants, or participated in speakers bureaus or advisory boards for the following pharmaceutical companies: Abbott, AstraZeneca, Forest, GSK, Janssen, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, Shire, and Novartis. Over the past 3 years, Drs Gopal, Gassmann-Mayer, Quiroz, Lim, and Yuen have been employed by Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ, and have stock or stock options in the company; Dr Eerdekens has been employed by Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium and holds stock and stock options in the company. Dr Hough was employed by Johnson & Johnson Pharmaceutical Research & Development, LLC, for all but the time from April 2008 to April 2009, during which he worked as an independent consultant. Dr Quiroz was employed by Johnson & Johnson Pharmaceutical Research & Development, LLC, from 2005 to June 2009 (which includes the period of this study) and has since been employed by Hoffman- LaRoche Pharma Development and Exploratory Neuroscience, Nutley, NJ.
Author Contributions: HAN was a principal investigator and the coordinating investigator for this study and contributed to data collection and interpretation and literature analysis. SG, JAQ, ME, EY, and DH contributed to study design and data interpretation. DH and SG wrote the protocol. CG-M and PL contributed to study design, and data analysis and interpretation. All authors contributed to writing and reviewing this report and approved the final paper.
Registration Information: This trial is registered at clinicaltrials.gov corresponding to NCT# 00101634.
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Previous presentations: Data from this study were presented at the American Psychiatric Association 161st Annual Meeting, 3–8 May 2008, and the 60th Institute of Psychiatric Services Annual Meeting, 2–5 October 2008.
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Nasrallah, H., Gopal, S., Gassmann-Mayer, C. et al. A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia. Neuropsychopharmacol 35, 2072–2082 (2010). https://doi.org/10.1038/npp.2010.79
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DOI: https://doi.org/10.1038/npp.2010.79
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