nonmem covariate analysis with placebo subjects

© 2015, The American College of Clinical Pharmacology. Within the range of covariate values investigated, pharmacokinetically driven adjustments of AMG 416 dosing on the basis of these covariates were not warranted.ĪMG 416 NONMEM calcium-sensing receptor pharmacokinetics secondary hyperparathyroidism. AMG 416 exhibits linear and stationary pharmacokinetics within the range of doses evaluated. Bootstrapping and predictive checks supported model predictive ability. 01) covariates effect was found on pharmacokinetic parameters. The mean time to achieve 90% steady-state predialysis concentrations with 3- and 6-hour hemodialysis TIW was 46 and 32 days, respectively. Only clinical trials satisfying the following criteria were included in the analysis: (1) enrolled subjects must be diagnosed with dementia caused by AD, (2) trials must use parallel design and blind methods with placebo as the control group, (3) trials must report 11 items on the ADAS-cog scale as the primary or secondary outcome, (4) the. The volume of distribution at steady-state was approximately 624 L (82%CV). Plasma clearance (interindividual variability) was 0.564 L/h (14.0%CV).

A 3-compartment linear pharmacokinetic model that accounts for the hemodialysis clearance best described the data. The predictability of the final model was evaluated using bootstrapping and visual predictive checks. The influence of demographics, concomitant medications, and other disease-related biomarkers on pharmacokinetic parameters was explored. AMG 416 doses ranging from 2.5 to 60 mg were administered intravenously as single or multiple thrice weekly (TIW) doses at the end of hemodialysis during rinseback. This study characterizes the population pharmacokinetics of AMG 416, an allosteric activator of the calcium-sensing receptor, in subjects with secondary hyperparathyroidism receiving hemodialysis.

Nonmem covariate analysis with placebo subjects