Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial.

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: Joris Berwaerts, Yanning Liu, Srihari Gopal, Isaac Nuamah, Haiyan Xu, Adam Savitz, Danielle Coppola, Alain Schotte, Bart Remmerie, Nataliya Maruta, David W Hough
• Journal: JAMA psychiatry (JAMA Psychiatry) Vol. 72 Issue 8 Pg. 830-9 (Aug 2015) ISSN: 2168-6238 [Electronic] United States
• PMID: 25820612 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Delayed-Action Preparations
• Isoxazoles
• Palmitates
• Paliperidone Palmitate

Topics

• Adolescent
• Adult
• Aged
• Antipsychotic Agents (administration & dosage, adverse effects, therapeutic use)
• Delayed-Action Preparations (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Isoxazoles (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Paliperidone Palmitate
• Palmitates (administration & dosage, adverse effects, therapeutic use)
• Schizophrenia (drug therapy, prevention & control)
• Secondary Prevention (methods)
• Treatment Outcome
• Young Adult