TABLE 1.
Parameter estimates for acalabrutinib and ACP‐5862 base and final model
| Final model OFV: 8345, condition no.: 24.7 | |||
|---|---|---|---|
| Parameter | Estimate (%RSE) | Bootstrap a | Shrinkage b |
| Fixed effects | |||
| CL/F (L/h) | 134 (1.97) | 132 [126, 139] | |
| Vc/F (L) | 31.0 (15.4) | 30.3 [25.3, 35.7] | |
| Q/F (L/h) | 20.9 (3.94) | 20.8 [18.6, 23.0] | |
| Vp/F (L) | 110 (3.45) | 108 [97.6, 120] | |
| Ka (h−1) | 1.48 (2.63) | 1.48 [1.41, 1.55] | |
| MTT (h) | 0.459 (4.16) | 0.460 [0.426, 0.492] | |
| CLM/F (L/h) | 21.8 (1.98) | 21.6 [20.2, 22.6] | |
| VcM/F (L) | 22.7 (6.66) | 22.7 [19.5, 25.8] | |
| QM/F (L/h) | 26.7 (8.65) | 26.4 [22.9, 29.9] | |
| VpM/F (L) | 89.2 (4.58) | 88.1 [77.6, 97] | |
| Covariate effects c | |||
| Healthy subject—CL/F | 0.467 (19.3) | 0.467 [0.367, 0.569] | |
| Healthy subject—Vp/F | −0.556 (5.59) | −0.554 [−0.6, −0.496] | |
| ECOG 2—CL/F | −0.171 (36.2) | −0.158 [−0.274, −0.032] | |
| PPI—F1 | −0.358 (7.01) | −0.368 [−0.49, −0.228] | |
| Random effects | |||
| BSV CL/F (CV%) | 23.8 (5.86) | 24.1 [20.4, 28] | 36.1 |
| BSV Vc/F (CV%) | 270 (6.51) | 284 [225, 367] | 25.9 |
| BSV Vp/F (CV%) | 33.7 (6.96) | 33.9 [25, 42.4] | 49.6 |
| BSV CLM/F (CV%) | 11.8 (21.1) | 13.1 [9.22, 20.2] | 70.2 |
| BSV VcM/F (CV%) | 47.2 (12.1) | 53.3 [36.9, 71.1] | 66.5 |
| BSV QM/F (CV%) | 40.7 (14.4) | 40 [23.8, 59.2] | 72.0 |
| BSV VpM/F (CV%) | 19.2 (30.5) | 21.2 [15.3, 41.2] | 79.6 |
| BOV MTT (CV%) | 118 (2.39) | 119 [104, 137] | 45.4 |
| BOV F1 (CV%) | 56.1 (1.80) | 55.3 [50.4, 61.1] | 42.4 |
| Residual error (SD) | 0.586 (0.558) | 0.583 [0.555, 0.612] | 13.0 |
| Residual error sparse (SD) | 0.856 (1.16) | 0.843 [0.762, 0.917] | 7.92 |
| Residual error metabolite (SD) | 0.334 (1.48) | 0.332 [0.304, 0.357] | 14.6 |
| Residual error metabolite sparse (SD) | 0.234 (4.25) | 0.225 [0, 0.325] | 37.4 |
Abbreviations: BOV, between‐occasion variability; BSV, between‐subject variability; CL/F, apparent clearance; CLM/F, apparent clearance metabolite; CV, coefficient of variation; ECOG, Eastern Cooperative Oncology Group; F1, relative bioavailability; Ka, first‐order absorption rate constant; MTT, mean transit time; OFV, objective function value; PPI, proton‐pump inhibitor; Q/F, apparent intercompartment clearance; QM/F, apparent intercompartment clearance metabolite; RSE, relative standard error; SD, standard deviation; Vc/F, apparent central volume of distribution; VcM/F, apparent central volume of distribution metabolite; Vp/F, apparent peripheral volume of distribution; VpM/F, apparent peripheral volume of distribution metabolite.
50th [2.5th, 97.5th percentile].
Shrinkage for BOV is provided as the mean of 4 occasions.
Relative change (1 + estimate).