Relative exposure A comparative assessment of systemic exposure of idarucizumab from clinical studies against the animal values is in Table 2. Human reference values are taken from several studies and included data from different patient groups, including elderly patients and patients with impaired renal function. Relative exposures attained in the animal studies (as AUC) were moderately low. Table 2. Systemic exposure of idarucizumab from clinical studies. Clinical exposure multiples Healthy Renal impairment volunteers 45 > – 64 64 yrs1 No. 500 Cmax: 7 6 6 7 DDB0136 181500 nM (11R091) , IV Rat (Wistar AUC: 107500 3 2 2 2 Han)NOAEL: nM 500 mg/kg/day, IV Study No. 150 Cmax: 2 2 2 2 U12-3328 nM Monkey IV AUC: 1 1 1 1 nM 500 Cmax: 9 8 7 9 235000 nM IV AUC: 223000 6 5 4 3 nM Study No. no Cmax: 6 6 5 6 U13-3376 159750 nM Monkey AUC: 173157 5 4 3 3 nM Cmax: 7 6 5 6 163000 nM AUC: 5 4 3 3 171000 nM No. no Cmax: 7 6 5 7 n00230533 174500 nM Monkey AUC: 202000 5 5 4 3 nM
Relative exposure A comparative assessment of systemic exposure of idarucizumab from clinical studies against the animal values is in Table 2. Human reference values are taken from several studies and included data from different patient groups, including elderly patients and patients with impaired renal function. Relative exposures attained in the animal studies (as AUC) were moderately low. Table 2. Systemic exposure of idarucizumab from clinical studies. Clinical exposure multiples Healthy volunteers Renal impairment 45 – 64 yrs1 > 64 No. DDB0136 (11R091) Rat (Wistar Han)NOAEL: 500 mg/kg/day, IV 500 IV Cmax: 181500 nM 7 6 6 7 AUC: 107500 nM 3 2 2 2 Study No. U12-3328 Monkey 150 IV Cmax: nM 2 2 2 2 AUC: nM 1 1 1 1 500 IV Cmax: 235000 nM 9 8 7 9 AUC: 223000 nM 6 5 4 3 Study No. U13-3376 Monkey no Cmax: 159750 nM 6 6 5 6 AUC: 173157 nM 5 4 3 3 Cmax: 163000 nM 7 6 5 6 AUC: 171000 nM 5 4 3 3 No. n00230533 Monkey no Cmax: 174500 nM 7 6 5 7 AUC: 202000 nM 5 5 4 3 ,
auspar-idarucizumab-161025.docx