title: Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier:NCT01529515.
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Joris
authors.initials: J
authors.lastname: Berwaerts
authors.affiliation: Johnson & Johnson Medical (China) Ltd, Beijing, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Srihari
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Isaac
authors.initials: I
authors.lastname: Nuamah
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Adam
authors.initials: A
authors.lastname: Savitz
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: Danielle
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Division of Janssen Pharmaceutica NV, Janssen Research & Development, Beerse, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Schotte
authors.affiliation: Division of Janssen Pharmaceutica NV, Janssen Research & Development, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Remmerie
authors.affiliation: Institute of Neurology, Psychiatry, and Narcology, Academy of Medical Science of Ukraine, Kharkiv, Ukraine.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Maruta
authors.affiliation: Janssen Research & Development, LLC, Titusville, New Jersey.
authors.forename: David W
authors.initials: DW
authors.lastname: Hough
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000517:prevention & control; D055502:Secondary Prevention / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D010168:Palmitates; D000068882:Paliperidone Palmitate