Table 2.
Structural parameter estimates for the models
| Population mean, θ (%RSE) | ||||
|---|---|---|---|---|
| Omalizumab or IgE parameter* | Control, constant | Exponential | Feedback interim | Feedback final |
| Clearance omalizumab, CLX/F (l day−1) | 0.214 | 0.207 (2.4) | 0.207 (2.3) | 0.206 (2.1) |
| Clearance IgE, CLE/F (l day−1) | 3.21 | 2.83 (3.5) | 2.83 (3.6) | 2.87 (4.3) |
| Clearance complex, CLC/F (l day−1) | 0.717 | 0.538 (3.5) | 0.533 (3.4) | 0.535 (4.3) |
| Volume omalizumab and IgE, VX/F and VE/F (l) | 9.41 | 8.61 (1.5) | 8.61 (1.5) | 8.62 (1.4) |
| Volume complex, VC/F) (l) | 7.15 (1.8)** | |||
| Absorption rate, ka (day−1) | 0.446 (3.2)** | |||
| Binding dissociation constant, Kd (nm) | 1.93 | 2.11 (4.5) | 2.10 (4.4) | 2.15 (4.7) |
| Kd change with total omalizumab to total IgE ratio, α | 0.0945 | 0.0635 (19) | 0.0659 (18) | 0.0532 (24) |
| IgE production prior to omalizumab, RB (µg day−1) | 982 | 966 (3.6) | 965 (3.6) | 967 (4.4) |
| IgE production at new equilibrium, RN (µg day−1) | – | 188 (31) | 168 (17) | 253 (13) |
| Rate of change in IgE production with omalizumab, kM (% year−1) | – | 53.9 (12) | 58.5 (5.1) | 53.8 (8.4) |
| Background (placebo) rate of change in IgE production, kE (% year−1) | 0.197 ± 1.47*** | |||
These analyses used data from studies in Table 1 except study Q0673g. Note that minimization for the control (constant) model terminated with errors and should be regarded cautiously. RSE, relative standard errors; these are missing from the control model as it terminated with rounding errors and did not run the $COV procedure.
Depending on covariate adjustment for each parameter, values are given for a 70 kg, 20 kgm−2 BMI, Caucasian male aged >12 years with baseline IgE value of 365 ng ml−1.
Values for VC and ka were fixed from a separate first order conditional with interaction estimation using data from single-dose bioequivalence studies.
The background rate of change in IgE production was estimated independently from the placebo data and was fixed in the estimation process; the standard error is shown on the original scale.