TABLE 2.
Final population PK and biomarker/efficacy model parameter estimates.
| PK model | ||
|---|---|---|
| Parameter, unit | Parameter estimates (RSE%) | Interindividual variability (RSE%) |
| CL in female patients with CD, a L/d | 0.26 (5%) | 0.131 (33%) |
| Effect of baseline albumin on CL | −1.32 (40%) | – |
| Effect of health status on CL | −0.362 (10%) | – |
| V c b in female subjects, L | 3.27 (5%) | 0.0502 (18%) |
| Effect of male gender on V c | 0.214 (37%) | – |
| V p, L | 2.64 (8%) | – |
| Q, L/d | 0.412 (19%) | – |
| k a, d−1 | 0.286 (11%) | – |
| T lag, d | 0.0296 (14%) | – |
| F | 0.88 (5%) | – |
| Proportional error | 24.9% (9%) | – |
| Biomarker/efficacy models | ||
|---|---|---|
| Parameter, unit | Parameter estimates (RSE%) | |
| IL‐22 | CRP | |
| Half‐life HL, day | 11.6 (33%) | 11.7 (8%) |
| Baseline CDAI | 318 (3%) | 318 (2%) |
| Inhibitory placebo effect | 0.209 (7%) | 0.178 (16%) |
| I max | 0.297 (30%) | 0.246 (10%) |
| IB50, pg/mL for IL‐22 and mg/L for CRP | 22.8 (10%) | 8.03 (10%) |
| Hill coefficient γ | 20 FIX | 2.07 FIX |
| IIV of BCDAI score (RSE%) | 0.0106 (74%) | 0.00997 (35%) |
| IIV of placebo effect (RSE%) | 0.0509 (26%) | 0.0519 (4%) |
| Correlation between IIV of BCDAI score and placebo effect | −100% | −100% |
| Proportional error, efficacy | 0.116 (42%) | 0.117 (9%) |
| Additive error, efficacy | 38.9 (28%) | 38.9 (8%) |
BCDAI, baseline Crohn's Disease Activity Index; CD, Crohn's disease; CDAI, Crohn's Disease Activity Index; CL, clearance; F, bioavailability; IB50, 50% of maximum unbound systemic concentration; I max, maximum inhibition; IIV, interindividual variability; k a, absorption rate constant; PK, pharmacokinetic; Q, intercompartmental clearance; RSE, relative standard error; V c, central volume of distribution; T lag, absorption lag time; V p, peripheral volume of distribution
Typical value for CL = 0.26 × (1–0.362 × health status) × (baseline albumin/39)−1.32 × exp (η1); for health status, patients with CD = 0, and healthy subjects = 1.
Typical value for V c = 3.27 × (1 + 0.214 × gender) × exp (η2); for gender, female = 0, and male = 1.