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Abstract
Abstract
Objective:
The purpose of this prospective study was to evaluate the effects of switching from oral risperidone to flexibly dosed oral paliperidone extended-release (ER) in Brazilian adults with schizophrenia because of lack of efficacy, intolerability, or nonadherence after a minimum trial of 30 days on adequate (labeled) doses of oral risperidone, according to individual clinical judgment.
Research design and methods:
Subjects with Positive and Negative Syndrome Scale total scores above 78, and/or intolerable adverse effects, with risperidone received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52 (extension phase) weeks.
Clinical trial registration:
Clinicaltrials.gov identifier: NCT01010776.
Results:
The intent-to-treat (efficacy) populations comprised 213 subjects in the main phase and 159 in the extension phase. Of 213 subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%) because of tolerability issues, according to individual clinical judgment. Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4 weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints, function improved from baseline to the first post-baseline visit (week 4) and remained significantly improved compared to baseline at each visit for paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported herein mainly for 26 and 52 weeks compared to baseline. Significant improvements from baseline were observed for the Positive and Negative Syndrome Scale total score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER also significantly improved health-related quality of life (Short-Form 36) from baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity (Clinical Global Impression–Severity; p < 0.0001 at each visit vs. baseline). Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the extension phase); increased body weight (10.7% and 12.6%, respectively); and anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment or interruption; and 3) decreased in frequency from the main to the extension phase.
Conclusions:
Oral paliperidone ER is a rational treatment alternative for patients with schizophrenia whose antipsychotic regimens are switched because of unsuccessful treatment with oral risperidone according to individual clinical judgment. Study limitations included the open-label study design, lack of placebo, and use of subjective clinical judgment to determine lack of efficacy, intolerability, or nonadherence with oral risperidone.
Transparency
Declaration of funding
The study was funded by Janssen-Cilag Farmacêutica Ltda., São Paulo, Brazil.
Declaration of financial/other relationships
J.A.d.O.C. has served as a paid investigator for AstraZeneca, Eli Lilly, Janssen-Cilag, Pfizer, Roche, and Servier, and served on advisory boards/speakers’ bureaus for Eli Lilly, Pfizer, and Janssen-Cilag. H.E. has received research grants from the São Paulo Research Foundation (FAPESP), Janssen-Cilag, Novartis, and Roche; served on speakers’ bureaus for Janssen-Cilag, Merck Sharp and Dohme, Novartis, and Roche; served on advisory boards for Janssen-Cilag, Lundbeck, Pfizer, and Roche; and received honoraria and travel support from Eli Lilly, Janssen-Cilag, and Novartis. D.Z.F. has received grants (and is a prospective grant recipient) from Janssen-Cilag. W.F.G.’s institution has received grants from FAPESP, and W.F.G. has received research grants from Janssen-Cilag, as well as consulting fees/honoraria/payments for lectures (e.g. for service on speakers’ bureaus) from FAPESP and EMS Pharmaceuticals, Brazil. A.L.T.L. has received grants and support for travel from Janssen-Cilag; is a member of boards for GlaxoSmithKline (GSK) and Eli Lilly; is a paid consultant to Moksha8; holds grants or pending grants from Eli Lilly, Bristol-Myers Squibb, and Servier; has served as a paid lecturer (including service on speakers’ bureaus) for Abbott, Eli Lilly, GSK, Janssen-Cilag, Medley, Lundbeck, and Moksha8; and has received other travel/accommodation/meeting support from AstraZeneca, Eli Lilly, and Janssen-Cilag. F.L.L. is an employee of, and minor shareholder in, Janssen-Cilag. M.R.L. has served on advisory or other boards/speakers’ bureaus for Janssen-Cilag, Pfizer, and Shire, and received grants and consulting fees/honoraria from Janssen-Cilag. I.R.d.O. has served as a paid consultant for Janssen-Cilag, Lundbeck, and Servier, and as a paid investigator for AstraZeneca, Eli Lilly, and Servier. C.d.A.-M.P. has served on advisory boards/speakers’ bureaus for AstraZeneca. J.Q. has received consulting fees/honoraria from Janssen-Cilag. F.L.R. is a paid (principal) investigator for AstraZeneca, Eli Lilly, Roche, and Servier, and has also served this function in the past for Janssen-Cilag and Pfizer. J.C.A. was an employee of Janssen-Cilag Farmacêutica Ltda., São Paulo, Brazil, when this trial was conducted and the manuscript prepared. S.I.R. has received grants from Quintiles, Servier, Teva and CPPSS. R.A.B., H.M.G., E.H., and E.S. Jr. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.
CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.
Acknowledgments
Assistance in manuscript preparation was provided by Stephen W. Gutkin, Rete Biomedical Communications Corp., Wyckoff, NJ, USA, with support from Janssen-Cilag Farmacêutica Ltda., São Paulo, Brazil. Statistical review and assistance were provided by Rita Antonelli Cardoso with support from Janssen-Cilag Farmacêutica Ltda. Dr. Márcio C. Versiani, of the Federal University of Rio de Janeiro, played a role in study conception and design; acquisition of data; and interpretation of data, but was physically unable to approve the final manuscript.
Notes
*Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., Titusville, NJ