Table 2.
Summary of key primary and secondary PK parameters (main PK population excluding ADA-positive patients, N = 230)
| Parameter (units) | Treatment | GLS mean | GLS mean ratio, % (91% CI) | ||
|---|---|---|---|---|---|
| DRL_RI/RTX-US | DRL_RI/RTX-EU | RTX-US/RTX-EU | |||
| PK population—primary end points | |||||
| AUC0–14 days, first infusion (µg h/mL) | DRL_RI | 42,380 | 100.80 (94.62–107.38) | 95.45 (89.60–101.68) | 94.69 (88.85–100.92) |
| RTX-US | 42,040 | ||||
| RTX-EU | 44,400 | ||||
| AUC0–∞, entire course (µg h/mL) | DRL_RI | 162,000 | 100.37 (92.30–109.14) | 93.58 (85.98–101.85) | 93.24 (85.62–101.54) |
| RTX-US | 161,500 | ||||
| RTX-EU | 173,200 | ||||
| AUC0–t, second infusion (µg h/mL) | DRL_RI | 118,100 | 101.55 (92.60–111.36) | 94.83 (86.52–103.93) | 93.38 (85.08–102.50) |
| RTX-US | 116,300 | ||||
| RTX-EU | 124,600 | ||||
| PK population—secondary end points | |||||
| AUC0–t, entire course (µg h/mL) | DRL_RI | 160,600 | 100.66 (92.71–109.30) | 94.24 (86.71–102.42) | 93.61 (86.11–101.77) |
| RTX-US | 159,600 | ||||
| RTX-EU | 170,400 | ||||
| Cmax, first infusion (µg/mL) | DRL_RI | 348.229 | 105.31 (98.70–112.37) | 100.25 (93.95–106.97) | 95.19 (89.17–101.61) |
| RTX-US | 330.659 | ||||
| RTX-EU | 347.370 | ||||
| Cmax, second infusion (µg/mL) | DRL_RI | 420.740 | 104.68 (98.17–111.63) | 102.26 (95.94–109.00) | 97.69 (91.53–104.26) |
| RTX-US | 401.926 | ||||
| RTX-EU | 411.447 | ||||
Main PK population, N = 230 (DRL_RI, n = 79; RTX-US, n = 73; RTX-EU, n = 78) The values are back-transformed from the log scale Results based on an ANOVA model with treatment (DRL_RI, RTX-US, and RTX-EU) region and gender being considered as fixed effects
ANOVA analysis of variance, AUC0–14 days area under the plasma concentration–time curve from time 0 to day 14, AUC0–t area under the plasma concentration–time curve from time 0 to last quantifiable concentration, AUC0–∞ area under the plasma concentration–time curve from time 0 extrapolated to infinite time, CI confidence interval, Cmax peak plasma concentration, GLS geometric least-squares, PK pharmacokinetic, RTX-US Rituxan®, RTX-EU MabThera®