Modeling the effectiveness of paliperidone ER and olanzapine in schizophrenia: meta-analysis of 3 randomized, controlled clinical trials.
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.
Ortega
Ignacio
I
Advanced Modeling and Simulation, Clinical Pharmacology Division, Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Perez-Ruixo
Juan Jose
JJ
Stuyckens
Kim
K
Piotrovsky
Vladimir
V
Vermeulen
An
A
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008960:Models, Psychological; D000077152:Olanzapine; D000068882:Paliperidone Palmitate; D025341:Principal Component Analysis; D011594:Psychometrics; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D001569:Benzodiazepines; D000077152:Olanzapine; D000068882:Paliperidone Palmitate