Table 1.
Effects of covariates on key pharmacokinetic parameters in the final covariate model
| Parameter | Covariate | Reference value for covariate * | Illustrative value for covariate * | Effect on parameter, % (mean, 95% CLs) |
|---|---|---|---|---|
| CLinf | Body weight | 75 kg | 52 kg | −20.9 (−26, −15.4) |
| 115 kg | 31.4 (21.6, 42) | |||
| Serum albumin | 40 g/L | 28.7 g/L | 25.4 (35.1, 16.4) | |
| 48.7 g/L | −12.6 (−16.3, −8.6) | |||
| Sex | Female | Male | 17.6 (9.8, 26) | |
| Disease type | FL or DLBCL | CLL | 46.9 (36.7, 57.9) | |
| SLL | 38 (10.2, 72.9) | |||
| MCL | 106.9 (44.6, 195.9) | |||
| Age | 65 years | 38 years | 13.8 (5.7, 22.6) | |
| 83 years | −5.7 (−8.9, −2.5) | |||
| Baseline tumour size | 3000 mm2 | 304 mm2 | −18.6 (−24.4, −12.4) | |
| 22 400 mm2 | 19.8 (12.3, 27.8) | |||
| CLT | Sex | Female | Male | 45.1 (19.3, 76.6) |
| Disease type | FL or DLBCL | CLL | 125.1 (72.3, 194.1) | |
| MCL | 180.3 (28, 513.7) | |||
| Baseline tumour size | 3000 mm2 | 304 mm2 | −55.2 (−64.8, −42.9) | |
| 22 400 mm2 | 102.3 (63.6, 150.1) | |||
| V1 | Body weight | 75 kg | 52 kg | −12.9 (−15.3, −10.5) |
| 115 kg | 17.5 (13.9, 21.4) | |||
| Sex | Female | Male | 19.4 (15.8, 23) | |
| V2 | Body weight | 75 kg | 52 kg | −32.6 (−39.7, −24.6) |
| 115 kg | 58.4 (39, 80.5) | |||
| Kdes | Received CHOP | No | Yes | −69.1 (−75.1, −61.6) |
| Received fludarabine + cyclophosphamide | No | Yes | 164.4 (38.5, 404.8) | |
| Received bendamustine | No | Yes | −40.9 (−55.5, −21.6) | |
| Disease type | FL or DLBCL | MZL | −70.1 (−81.9, −50.7) |
CHOP: cyclophosphamide, doxorubicin, vincristine and prednisone; CL: confidence limit; CLinf: nonspecific time‐independent clearance; CLT: initial value of time‐dependent clearance; CLL: chronic lymphocytic leukaemia; DLBCL: diffuse large B‐cell lymphoma; FL: follicular lymphoma; kdes: decay coefficient of time‐dependent clearance; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; PK: pharmacokinetic; SLL: small lymphocytic lymphoma; V1: central volume of distribution; V2: peripheral volume of distribution.
For continuous covariates, reference values are medians and illustrative values are the 2.5th and 97.5th percentiles of the values in the analysis data set.