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Modeling the Effectiveness of Paliperidone ER and Olanzapine in Schizophrenia: Meta‐Analysis of 3 Randomized, Controlled Clinical Trials
Author(s) -
Ortega Ignacio,
PerezRuixo Juan Jose,
Stuyckens Kim,
Piotrovsky Vladimir,
Vermeulen An
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009346057
Subject(s) - paliperidone , olanzapine , positive and negative syndrome scale , placebo , paliperidone palmitate , schizophrenia (object oriented programming) , population , medicine , randomized controlled trial , psychology , antipsychotic , psychiatry , psychosis , alternative medicine , environmental health , pathology
The time course of Positive and Negative Syndrome Scale (PANSS) scores in adult schizophrenia patients was modeled, and the effectiveness of paliperidone extended‐release tablets (paliperidone ER) and olanzapine was quantified. Data from 3 randomized, double‐blind phase III studies were used. Patients received paliperidone ER (3, 6, 9, 12, or 15 mg), olanzapine 10 mg, or matched placebo once daily for 6 consecutive weeks. An indirect response model implemented using a nonlinear mixed effects approach described the time course of the PANSS. Deterioration rate was modeled as a function of baseline PANSS score, placebo, and drug effects, and the dropout effect. An exponential decrease of the placebo response was also implemented. Paliperidone ER and olanzapine treatment were characterized by a long‐lasting drug effect (13%), with a larger but short‐lasting placebo effect (40%) and a notable dropout rate. The covariate exploration failed to identify any clinically relevant factors. The nonparametric bootstrap analysis confirmed the acceptable precision of parameter estimates. The visual predictive check supported the model's adequacy to reproduce observed PANSS time courses. The population model describes the time course of PANSS scores in schizophrenia patients and is appropriate for use in clinical trial simulation activities.