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Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial.
JAMA Psychiatry. 2015 Aug; 72(8):830-9.JP

Abstract

IMPORTANCE

Treatment nonadherence and relapse are common problems in patients with schizophrenia. The long-acting 3-month formulation of paliperidone palmitate, owing to its extended elimination half-life, may offer a valuable therapeutic option for these patients.

OBJECTIVE

To evaluate the efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo in delaying time to relapse of schizophrenia symptoms.

DESIGN, SETTING, AND PARTICIPANTS

This randomized, multicenter trial conducted from April 26, 2012, through April 9, 2014, in 8 countries consisted of 4 phases: 3-week screening phase, flexible-dose 17-week open-label transition phase, 12-week open-label maintenance phase, and open-ended double-blind (DB) phase. Of the 506 patients enrolled (aged 18-70 years; DSM-IV-TR diagnosis of schizophrenia), 305 were randomized to 3-month paliperidone palmitate (n = 160) or placebo (n = 145) in the DB phase.

INTERVENTIONS

Patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg eq) during the transition phase, followed by a single dose of the 3-month formulation (3.5 times the stabilized dose of once-monthly paliperidone palmitate) during the maintenance phase. Stabilized patients were randomized to receive either a fixed dose of 3-month paliperidone palmitate (175, 263, 350, or 525 mg eq) or placebo once every 3 months during the DB phase.

MAIN OUTCOMES AND MEASURES

Time from randomization to the first relapse event (time to relapse) in the DB phase.

RESULTS

In the interim analysis, time to first relapse was significantly different in favor of the paliperidone palmitate group vs the placebo group (hazard ratio = 3.45; 95% CI, 1.73-6.88; P < .001); median time to relapse was 274 days for placebo but not estimable for 3-month paliperidone palmitate. An independent data monitoring committee recommended early study termination due to efficacy. In the DB phase, 183 of 305 patients (62% with 3-month paliperidone palmitate; 58% with placebo) had at least 1 treatment-emergent adverse event; those noted more frequently in the group receiving paliperidone palmitate than in the placebo group were headache (9% vs 4%), weight increased (9% vs 3%), nasopharyngitis (6% vs 1%), and akathisia (4% vs 1%).

CONCLUSIONS AND RELEVANCE

Compared with placebo, the 3-month formulation of paliperidone palmitate administered 4 times yearly significantly delayed time to relapse in patients with schizophrenia. The 3-month formulation was generally tolerable and has a safety profile consistent with other marketed paliperidone formulations.

TRIAL REGISTRATION

clinicaltrials.gov Identifier:NCT01529515.

Authors+Show Affiliations

Janssen Research & Development, LLC, Titusville, New Jersey.Johnson & Johnson Medical (China) Ltd, Beijing, China.Janssen Research & Development, LLC, Titusville, New Jersey.Janssen Research & Development, LLC, Titusville, New Jersey.Janssen Research & Development, LLC, Titusville, New Jersey.Janssen Research & Development, LLC, Titusville, New Jersey.Janssen Research & Development, LLC, Titusville, New Jersey.Division of Janssen Pharmaceutica NV, Janssen Research & Development, Beerse, Belgium.Division of Janssen Pharmaceutica NV, Janssen Research & Development, Beerse, Belgium.Institute of Neurology, Psychiatry, and Narcology, Academy of Medical Science of Ukraine, Kharkiv, Ukraine.Janssen Research & Development, LLC, Titusville, New Jersey.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25820612

Citation

Berwaerts, Joris, et al. "Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate Vs Placebo for Relapse Prevention of Schizophrenia: a Randomized Clinical Trial." JAMA Psychiatry, vol. 72, no. 8, 2015, pp. 830-9.
Berwaerts J, Liu Y, Gopal S, et al. Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2015;72(8):830-9.
Berwaerts, J., Liu, Y., Gopal, S., Nuamah, I., Xu, H., Savitz, A., Coppola, D., Schotte, A., Remmerie, B., Maruta, N., & Hough, D. W. (2015). Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry, 72(8), 830-9. https://doi.org/10.1001/jamapsychiatry.2015.0241
Berwaerts J, et al. Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate Vs Placebo for Relapse Prevention of Schizophrenia: a Randomized Clinical Trial. JAMA Psychiatry. 2015;72(8):830-9. PubMed PMID: 25820612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial. AU - Berwaerts,Joris, AU - Liu,Yanning, AU - Gopal,Srihari, AU - Nuamah,Isaac, AU - Xu,Haiyan, AU - Savitz,Adam, AU - Coppola,Danielle, AU - Schotte,Alain, AU - Remmerie,Bart, AU - Maruta,Nataliya, AU - Hough,David W, PY - 2015/3/31/entrez PY - 2015/3/31/pubmed PY - 2015/10/31/medline SP - 830 EP - 9 JF - JAMA psychiatry JO - JAMA Psychiatry VL - 72 IS - 8 N2 - IMPORTANCE: Treatment nonadherence and relapse are common problems in patients with schizophrenia. The long-acting 3-month formulation of paliperidone palmitate, owing to its extended elimination half-life, may offer a valuable therapeutic option for these patients. OBJECTIVE: To evaluate the efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo in delaying time to relapse of schizophrenia symptoms. DESIGN, SETTING, AND PARTICIPANTS: This randomized, multicenter trial conducted from April 26, 2012, through April 9, 2014, in 8 countries consisted of 4 phases: 3-week screening phase, flexible-dose 17-week open-label transition phase, 12-week open-label maintenance phase, and open-ended double-blind (DB) phase. Of the 506 patients enrolled (aged 18-70 years; DSM-IV-TR diagnosis of schizophrenia), 305 were randomized to 3-month paliperidone palmitate (n = 160) or placebo (n = 145) in the DB phase. INTERVENTIONS: Patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg eq) during the transition phase, followed by a single dose of the 3-month formulation (3.5 times the stabilized dose of once-monthly paliperidone palmitate) during the maintenance phase. Stabilized patients were randomized to receive either a fixed dose of 3-month paliperidone palmitate (175, 263, 350, or 525 mg eq) or placebo once every 3 months during the DB phase. MAIN OUTCOMES AND MEASURES: Time from randomization to the first relapse event (time to relapse) in the DB phase. RESULTS: In the interim analysis, time to first relapse was significantly different in favor of the paliperidone palmitate group vs the placebo group (hazard ratio = 3.45; 95% CI, 1.73-6.88; P < .001); median time to relapse was 274 days for placebo but not estimable for 3-month paliperidone palmitate. An independent data monitoring committee recommended early study termination due to efficacy. In the DB phase, 183 of 305 patients (62% with 3-month paliperidone palmitate; 58% with placebo) had at least 1 treatment-emergent adverse event; those noted more frequently in the group receiving paliperidone palmitate than in the placebo group were headache (9% vs 4%), weight increased (9% vs 3%), nasopharyngitis (6% vs 1%), and akathisia (4% vs 1%). CONCLUSIONS AND RELEVANCE: Compared with placebo, the 3-month formulation of paliperidone palmitate administered 4 times yearly significantly delayed time to relapse in patients with schizophrenia. The 3-month formulation was generally tolerable and has a safety profile consistent with other marketed paliperidone formulations. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01529515. SN - 2168-6238 UR - https://www.unboundmedicine.com/medline/citation/25820612/Efficacy_and_Safety_of_the_3_Month_Formulation_of_Paliperidone_Palmitate_vs_Placebo_for_Relapse_Prevention_of_Schizophrenia:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2015.0241 DB - PRIME DP - Unbound Medicine ER -