Articles
Clinical Pharmacology & Therapeutics (2008); 83, 6, 857–866 doi:10.1038/sj.clpt.6100374
Modeling and Simulation to Support Dose Selection and Clinical Development of SC-75416, a Selective COX-2 Inhibitor for the Treatment of Acute and Chronic Pain
KG Kowalski1, S Olson2, AE Remmers3 and MM Hutmacher1
- 1Global Pharmacometrics, Pfizer Inc., Michigan, USA
- 2Clinical Pharmacology, Pfizer Inc., Michigan, USA
- 3Array Biopharma, Boulder, Colorado, USA
Correspondence: KG Kowalski, (ken.kowalski@pfizer.com)
Received 25 May 2007; Accepted 8 August 2007; Published online 19 September 2007.
Abstract
Pharmacokinetic/pharmacodynamic (PK/PD) models were developed and clinical trial simulations were conducted to recommend a study design to test the hypothesis that a dose of SC-75416, a selective cyclooxygenase-2 inhibitor, can be identified that achieves superior pain relief (PR) compared to 400 mg ibuprofen in a post–oral surgery pain model. PK/PD models were developed for SC-75416, rofecoxib, valdecoxib, and ibuprofen relating plasma concentrations to PR scores using a nonlinear logistic-normal model. Clinical trial simulations conducted using these models suggested that 360 mg SC-75416 could achieve superior PR compared to 400 mg ibuprofen. A placebo- and positive-controlled parallel-group post–oral surgery pain study was conducted evaluating placebo, 60, 180, and 360 mg SC-75416 oral solution, and 400 mg ibuprofen. The study results confirmed the hypothesis that 360 mg SC-75416 achieved superior PR relative to 400 mg ibuprofen (
TOTPAR6=3.3, P<0.05) and demonstrated the predictive performance of the PK/PD models.
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