Phoenix winnonlin version

The following PD and PK parameters were derived from the noncompartmental method using Phoenix^® WinNonlin^® version 8.2 (Certara, St. Louis, MO, USA). The degree of platelet aggregation maximally inhibited by aspirin (i.e., maximum platelet aggregation (%)) was defined as the value of the lowest platelet aggregation (%) in each individual subject and determined from the observed platelet aggregation-time profiles. The area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC_last) or the AUC for a dosing interval at steady state (AUC_τ,ss) was calculated by the linear-up and log-down trapezoidal rule, and the AUC from 0 to infinity (AUC_inf) was calculated as the sum of AUC_last and the last measurable concentration divided by the terminal elimination rate constant (λ_z). The maximum plasma concentration (C_max) or C_max at steady state (C_max,ss) and the time to reach C_max or C_max,ss (T_max or T_max,ss) were obtained directly from the observed plasma concentration-time profiles. The terminal elimination half-life (t_1/2) or the t_1/2 at steady state (t_1/2,ss) was calculated as ln (2) divided by λ_z. The metabolic ratio was calculated as the AUC_last or AUC_τ,ss ratio of the respective metabolite to the parent molecule.

Pharmacokinetic parameters were derived from non-compartmental analysis using Phoenix WinNonlin version 8.0 (Certara, Princeton, NJ, USA). The peak plasma concentration (C_max) was determined by visual inspection of the data from the concentration–time curves. The linear trapezoidal rule was used to obtain the area under the plasma concentration–time curve (AUC). The C_max to baseline ratio (C_maxR) instead of the reference method that relies on the AUC to control ratio (AUCR) was used to evaluate the modulation of OATP1B function, as samples from an untreated group were not available in our study, and previous studies [13 (link),20 (link)] reported that such an approach provides data of equivalent utility. In the calculation of C_max ratio of the endogenous biomarkers, the control values were set as the baseline concentration of corresponding patient.

Descriptive statistics were used for participant characteristics, serum concentrations of nipocalimab and total IgG, derived PK parameters (as appropriate), laboratory tests, ECG, and vital signs. PK parameters were calculated from the serum nipocalimab concentration-time data using noncompartmental analysis (Phoenix® WinNonlin®, version 7.0; Certara, Princeton, NJ, USA). All statistical analysis and reporting were generated using SAS for Windows, version 9.4 (SAS Institute, Cary, NC, USA).

Plasma PK samples were collected predose and 0.5, 1, 2, 4, 6, and 8 h postdose on days 1 and 14 of the first cycle and predose only on days 2, 8, 15, and 16. Participants fasted for 8 h before taking study drug in the clinic and fasted for 1 additional hour after. The plasma samples were assayed by a validated liquid chromatography–tandem mass spectrometry method with a linear validated range of 1 to 1000 nM in human plasma. Standard noncompartmental PK methods were used to analyze pemigatinib plasma concentration versus time data using Phoenix^® WinNonlin^® version 8.0 (Certara USA Inc.).