Table 3.
Pantoprazole pharmacokinetics.
| PK parameters† | Total (n = 20) | Clazakizumab (n = 10) | Placebo (n = 10) |
|---|---|---|---|
| Day 0 | |||
| T1/2 (h) | 1.08 (0.86–1.72) | 1.55 (0.98–3.09) | 0.94 (0.76–1.33) |
| Cmax (μg/ml) | 1.49 (1.10–2.59) | 1.66 (1.07–3.45) | 1.37 (1.08–2.44) |
| AUC0‐last (μg/ml*h) | 2.88 (1.82–4.02) | 3.67 (1.76–9.18) | 2.71 (1.70–3.32) |
| AUC0‐inf (μg/ml*h) | 3.16 (2.21–7.84) | 4.21 (2.11–13.01) | 3.14 (2.31–3.94) |
| Week 12 | |||
| T1/2 (h) | 1.08 (0.97–1.9) | 1.90 (0.98–3.86) | 1.0 (0.84–1.19) |
| Cmax (μg/ml) | 1.45 (1.09–2.83) | 1.66 (0.98–3.02) | 1.38 (1.26–2.0) |
| AUC0‐last (μg/ml*h) | 2.70 (1.75–5.41) | 3.45 (1.62–11.39) | 2.05 (1.74–3.92) |
| AUC0‐inf (μg/ml*h) | 3.66 (2.03–7.52) | 6.67 (2.47–20.65) | 2.33 (1.91–4.43) |
| Week 52 | |||
| T1/2 (h) | 1.03 (0.89–2.10) | 2.10 (1.41–2.98) | 0.89 (0.80–1.00) |
| Cmax (μg/ml) | 1.97 (0.99–2.89) | 2.75 (1.49–3.82) | 1.57 (0.93–2.32) |
| AUC0‐last (μg/ml*h) | 3.82 (1.78–7.10) | 6.87 (2.79–12.98) | 2.37 (1.72–4.17) |
| AUC0‐inf (μg/ml*h) | 4.22 (1.99–8.18) | 8.09 (2.92–20.60) | 2.75 (1.84–4.66) |
| Percent change from day 0 to week 12 | |||
| T1/2 | 5.9 (−4.5–23.2) | 18.4 (−0.4–23.2) | 0.2 (−14.4‐21.5) |
| Cmax | 2.1 (−12.2‐26.3) | ‐7.6 (−16.2‐17.4) | 5.7 (−10.7‐41.3) |
| AUC0‐last | 10.4 (−8.0‐27.8) | ‐1.8 (−7.9‐27.9) | 15.6 (−18.7‐31.1) |
| AUC0‐inf | 11.6 (−11.7‐31.4) | 4.0 (−6.4‐80.3) | 13.8 (−17.7‐27.8) |
| Percent change from day 0 to week 52 | |||
| T1/2 | ‐0.3 (−19.9‐19.2) | 8.8 (−9.7‐56.8) | ‐9.8 (−34.1‐14.8) |
| Cmax | 5.5 (−22.1‐33.6) | 22.5 (1.6‐37.8) | ‐8.8 (−43.5‐44.5) |
| AUC0‐last | 25.3 (−15.9–51.7) | 41.9 (0.4–84.5) | 13.6 (−47.2–50.5) |
| AUC0‐inf | 31.9 (−22.5–64.0) | 52.3 (−5.6–64.1) | 0.72 (−42.7–64.0) |
Results are provided as median and interquartile range. With the exception of T1/2 at 52 weeks (P = 0.01), inter‐group differences with respect to PK parameters (clazakizumab versus placebo; Mann–Whitney U‐test) were not significant (P > 0.05). Changes from baseline to week 52 (overall study cohort; paired analysis applying Wilcoxon test) were nonsignificant (P > 0.05).
AUC0‐last, area under plasma concentration from zero hours to the last measurable concentration; AUC0‐inf, AUC extrapolated to infinity; Cmax, maximum plasma concentration; PK, pharmacokinetics.
†
Pantoprazole PK at baseline and at week 12 was available for all patients, at 52 weeks for 18 subjects, following study withdrawal of two study patients.