Table 2.
Projected steady‐state cinpanemab serum AUCtau, steady‐state Cmax, and safety margins for phase II doses
| Dose, mg | Projected parameters | Safety margins a | ||
|---|---|---|---|---|
|
Median (q5–q95) AUCtau, h*µg/mL |
Median (q5–q95) Cmax, µg/mL |
Median (q5‐q95) AUCtau, h*µg/mL |
Median (q5–q95) Cmax, µg/mL |
|
| Phase II study | ||||
| 250 | 42,700 (27,400–68,200) | 175 (111–276) | 131 (204–82) | 114 (180–72) |
| 1,250 | 214,000 (135,000–337,000) | 882 (573–1,450) | 26 (41–17) | 23 (35–14) |
| 3,500 | 612,000 (386,000–960,000) | 2,480 (1,630–3,930) | 9 (15–6) | 8 (12–5) |
| Japanese FIH study | ||||
| 1,250 | 371,580 (276,340–504,370) | 1,020 (790–1,360) | 15 (20–11) | 20 (15–25) |
| 3,500 | 1,015,600 (761,000–1,347,000) | 2,840 (2,160–3,700) | 5 (7–4) | 7 (9–5) |
AUCtau, area under the concentration‐time curve from time zero to the time of next dosing; Cmax, maximum observed concentration; FIH, first‐in‐human; q, percentile.
a
Calculated based on mean AUC0–168h and Cmax after the last dose of cinpanemab in the 26‐week rat toxicology study. AUCtau at no‐observed‐adverse‐effect level = AUC0–168h*4 = 5,580,000 h*µg/mL.; Cmax = 20,000 µg/mL.