5. Relative exposure to fidaxomicin at the end of repeat-dose toxicity studies Species Study Dose AUClast Exposure duration (mg/kg/day) (µg.h/mL) ratio# AUC Actual or Nominal Dog 58 N 0.09 14 days PO 1 beagle WIL- Capsule 144 N 0.3 4 461 N 2 24 771 N 4.7 14 days PO 58 Capsule 1067 N 16 196 30 N 2.4 7.6 – 14 days PO 29-93 gavage 60 N 1.7 8.5 – 21-104 120 N 6 73 108 N 0.7 3 PO 9 Gavage 364 N 5.4 66 1038 N 11.2 137 Monkey 34 A 0.25 4 weeks PO 3 Cynomolgus capsule 102 A 0.75 9 [400 mg] Human Single PO 0.0817 healthy dose volunteers # = animal:human plasma AUC0–24 h ; ND-not detected in plasma, LLOQ=0.5 µg/mL 6. Relative exposure to the fidaxomicin metabolite OP-1118 in repeat-dose toxicity studies Species Study Nominal Dose AUC0–last AUC exposure duration (mg/kg/day) (µg.h/mL) ratio# (number) AUC Dog 460 0.3 14 days PO 0.045 (beagle) Capsule 771 2 14 days PO 0.4 1067 10 capsule 1.8 30 0.3-0.8 2-5 60 0.06-0.6 0.3-3
5. Relative exposure to fidaxomicin at the end of repeat-dose toxicity studies Species Study duration Dose (mg/kg/day) Actual or Nominal AUClast (µg.h/mL) Exposure ratio# AUC Dog beagle 14 days PO Capsule 58 N 0.09 1 144 N 0.3 4 461 N 2 24 14 days PO Capsule 771 N 4.7 58 1067 N 16 196 14 days PO gavage 30 N 2.4 – 7.6 29-93 60 N 1.7 – 8.5 21-104 120 N 6 73 3 PO Gavage 108 N 0.7 9 364 N 5.4 66 1038 N 11.2 137 Monkey Cynomolgus 4 weeks PO capsule 34 A 0.25 3 102 A 0.75 9 Human healthy volunteers Single dose PO [400 mg] 0.0817 # = animal:human plasma AUC0–24 h ; ND-not detected in plasma, LLOQ=0.5 µg/mL 6. Relative exposure to the fidaxomicin metabolite OP-1118 in repeat-dose toxicity studies Species Study duration (number) Nominal Dose (mg/kg/day) AUC0–last (µg.h/mL) AUC exposure ratio# AUC Dog (beagle) 14 days PO Capsule 460 0.045 0.3 14 days PO capsule 771 0.4 2 1067 1.8 10 30 0.3-0.8 2-5 60 0.06-0.6 0.3-3 WIL-
auspar-fidaxomicin-130926.docx