Table 2.
Estimated JNJ-8104, CNTO148 and CNTO 6785 cynomolgus monkey PK/TE model parameters (mean, residual standard error%) and predicted human parameters.
Parameter (unit) | JNJ-8104 Human, predicted (observed human PK) |
JNJ-8104 Human, predicted (allometric scaling) |
JNJ-8104 Cyno, estimated |
Golimumab Cyno, estimated |
CNTO 6785 Cyno, estimated |
---|---|---|---|---|---|
CL (L/day/kg) | 0.00549 | 0.0048 * | 0.0077 (4%) | 0.0131 (10%) | 0.0072 (14%) |
V1 (L/kg) | 0.0464 | 0.0375 * | 0.0375 (5%) | 0.0588 (4%) | 0.0405 (6%) |
V2 (L/kg) | 0.0341 | 0.0217 * | 0.0217 (9%) | 0.0342 (9%) | 0.0302 (5%) |
Q (L/day/kg) | 0.00598 | 0.0140 * | 0.0224 (11%) | 0.0353 (11%) | 0.023 (9%) |
TNFα | |||||
kdeg (1/day) | 271.18 * | 271.18 * | 596 ● | 596 ● | |
Baseline (pg/mL) | 0.9^^ | 0.9^^ | 0.612 ^ | 0.612 ^ | |
kel_complex (1/day) | 0.12 | 0.17* | 0.365 ● | 0.365 ● | |
KD (pM) | 1610 ʘ | 1610 ʘ | 1610 (10%) | 65.7 (10%) | |
IL-17A | |||||
kdeg (1/day) | 45.50 * | 45.50 * | 100 # | 100 (31%) | |
Baseline (pg/mL) | 1.365^^^ | 1.365^^^ | 0.763 (29%) | 1.365 ^ | |
kel_complex (1/day) | 0.12 | 0.14 * | 0.317 (25%) | 0.504 (39%) | |
KD (pM) | 254 ʘ | 254 ʘ | 254 (21%) | 38.9 (41%) |
The PK data points under apparent impact of ADA were excluded for estimating human PK parameters based on JNJ-61178104 observed PK in the FIH study.
kel_complex was based on the estimated human PK parameters assuming that kel_complex for both targets was the same as the elimination rate constant of JNJ-8104 (e.g., calculated as CL/V1).
*Scaled from JNJ-8104 cyno parameters using BW-based allometric scaling with fixed exponents.
ʘ fixed at the estimated parameter values based on JNJ-8104 cyno model fitting.
^^ fixed at the reported population median value for TNFα baseline in RA patients.40
^^^ assumed to be the same as cynos and fixed at the observed mean IL-17A baseline in cynos
● fixed based on mathematical derivations using observed data, see section “TMDD model for TNFα” for details.
^ fixed at the observed mean baseline levels for TNFα or IL-17A in cynos
# fixed at the estimated parameter value based on CNTO 6785 cyno model fitting.