Citation

Rui Q, Wang Y, Liang S, Liu Y, Wu Y, Wu Q, Nuamah I, Gopal S. Prog. Neuropsychopharmacol. Biol. Psychiatry 2014; 53: 45-53.

Copyright

(Copyright © 2014, Elsevier Publishing)

DOI

10.1016/j.pnpbp.2014.02.007

PMID

unavailable

Abstract

OBJECTIVES: The objective of this study was to evaluate the long-term efficacy, safety, and tolerability of paliperidone extended-release (pali ER), in Chinese patients with schizophrenia.

METHODS: In this parallel-group, relapse prevention, phase-3 study (screening [14-day], pali ER open-label run-in [8-week] and stabilization [6-week] phases, and double-blind (DB) treatment [variable duration], and open-label extension phases [24-week]), 136/201 patients with schizophrenia were randomized (1:1) to pali ER (3-12. mg) or placebo during the DB phase.

RESULTS: Final analysis showed that, out of 135 patients in ITT (DB) population, 71 (52.6%) had a relapse event, 45 (33.3%) were ongoing at the time the study was stopped, and 19 (14.1%) discontinued from the DB phase. Time to relapse (primary endpoint) favored pali ER (hazard ratio. = 5.23 [95% CI: 2.96, 9.25], p < 0.0001). Rate of relapses (55/71 [77.5%] placebo; 16/64 [25%] pali ER) and secondary endpoints (change from baseline in Positive And Negative Syndrome Scale [PANSS] and Clinical Global Impression - Severity Scores) were significantly lower (p. < 0.001) in pali ER group vs placebo, in favor of pali ER. More psychiatric-related treatment-emergent adverse events (TEAEs) occurred in placebo- (21.1%) than pali ER group (10.9%). Most common (>. 3%) TEAEs in placebo group were insomnia and schizophrenia (8.5% each), while in pali ER group were aggression and akathisia (4.7% each), and schizophrenia, tremor, nausea, amenorrhea, and salivary hypersecretion (3.1% each). All serious TEAEs were psychiatric-related (schizophrenia, aggression, completed suicide, auditory hallucination, suicide attempt) and more frequent in placebo- (11.3%) versus pali ER group (3.1%). Death and tardive dyskinesia-related discontinuation (n = 1 each) occurred in placebo group. Body weight increase from run-in baseline was greater in pali ER group (mean increase: 3.90. kg) versus placebo (mean increase: 2.05. kg).

CONCLUSIONS: This study confirms the findings from earlier pali ER global relapse-prevention studies and demonstrates that pali ER treatment (3-12. mg) is efficacious over the long-term and significantly delays relapse in Chinese patients with schizophrenia. No new safety signals were detected in this population. © 2014 The Authors.

Language: en

Keywords

Humans; adolescent; Adult; Aged; Female; Male; Middle Aged; adult; human; age; Adolescent; suicide; female; male; Age Factors; Young Adult; aged; Proportional Hazards Models; Kaplan-Meier Estimate; Analysis of Variance; Double-Blind Method; Schizophrenia; suicidal ideation; depression; aggression; schizophrenia; anxiety; psychosis; randomized controlled trial; suicide attempt; clinical trial; Symptoms; Recurrence; Dose-Response Relationship, Drug; epilepsy; article; major clinical study; controlled study; neuroleptic agent; sexual dysfunction; prolactin; weight reduction; double blind procedure; hallucination; phase 3 clinical trial; middle aged; recurrent disease; constipation; drug safety; placebo; drug efficacy; extrapyramidal symptom; drug tolerability; nausea; tremor; weight gain; hypersalivation; drug withdrawal; multicenter study; akathisia; restlessness; irritability; relapse; galactorrhea; menstrual irregularity; parkinsonism; QT prolongation; controlled release formulation; glucose; dose response; Chinese; Antipsychotic Agents; unspecified side effect; auditory hallucination; analysis of variance; libido disorder; Asian Continental Ancestry Group; systolic blood pressure; amenorrhea; drug dose increase; open study; Clinical Global Impression scale; proportional hazards model; hyperkinesia; Positive and Negative Syndrome Scale; Kaplan Meier method; Pyrimidines; parallel design; pulse rate; pyrimidine derivative; drug delivery system; young adult; rhinopharyngitis; Drug Delivery Systems; paliperidone; Paliperidone; Isoxazoles; isoxazole derivative; Asian continental ancestry group; extended release tablet; oropharynx pain; synesthetic hallucination; Time to relapse