TABLE 3.
Parameter estimates of the final BTKO model for evobrutinib at week 48
| Parameter | Estimate | RSE (%) | 95% CI |
|---|---|---|---|
| K out (1/h) | 0.00346 | 5.98 | 0.00305–0.00387 |
| K irrev (ml/ng/h) | 0.0146 | 6.27 | 0.0128–0.0164 |
| Inter‐individual variability | Estimate (RSE%) | Etabar (SE) | CV% | Shr% |
|---|---|---|---|---|
| ω2 K out | 0.350 (30.3) | 0.00774 (0.0442) | 64.7 | 20.5 |
| ω2 K irrev | 0.209 (29.7) | 0.000315 (0.0329) | 48.2 | 23.5 |
| Residual variability | Estimate | RSE % | 95% CI | CV% |
|---|---|---|---|---|
| Additive error | 0.00180 | 9.89 | 0.00145–0.00215 | – |
| Proportional error | 0.617 | 9.69 | 0.500–0.734 | 61.7 |
Note: Residual error terms were estimated as thetas (point estimate is √ω2). As ω2 > 0.15, CV% = 100 *√eω2 − 1.
Abbreviations: BTKO, Bruton's tyrosine kinase occupancy; CI, confidence interval; CV%, coefficient of variation (%); Etabar, arithmetic mean of the η estimates; K out, first‐order elimination rates of BTK protein; K irrev, second‐order irreversible binding rate constant; %RSE, percent relative standard error of the estimate (standard error/parameter estimate × 100); Shr, shrinkage; ω2 K out and ω2 K irrev, variance of random effect of K out and K irrev, respectively.