and 200 mg BID (NSCLC) and estimated AUC and Cmax values obtained from the Summary of Clinical Pharmacology Studies, where AUC0-12 was 1.82 ng∙h/mL/mg and Cmax was 0.280 ng/mL/mg in IPF patients and AUC0-12 was 2.03 ng∙h/mL/mg and Cmax was 0.282 ng/mL/mg in NSCLC patients; bold and underlined dose was NOAEL; NA = not applicable. Trial 5. Exposures to BIBF 1202 glucuronide in oral repeat dose toxicity and carcinogenicity studies. Species Dose Cmax Exposure Exposure duration ng/mL h ratio# IPF ratio# NSCLC time of ng∙h/mL indication indication on on on on AUC AUC Mouse 13 weeks 10 63.3 197.5 0.28 0.04 0.21 0.03 (Day 87) 30 228.5 968.5 1.0 0.22 0.75 0.16 100 1011 5050 4.4 1.2 3.3 0.86 5 16.5 42.7 0.07 0.01 0.05 0.01 (week 26) 15 78.6 399.5 0.34 0.09 0.26 0.07 30 213.5 1291 0.94 0.29 0.70 0.22 Rat 13 weeks 5 780.5 2065 3.4 0.47 2.6 0.35 (Day 87) 20 2425 8150 11 1.9 8.0 1.4 60 6865 30000 30 6.8 23 5.1 26 weeks 5 ND ND - - - - (Day 20 ND ND - - - - 80 ND ND - - - - 2.5 295.5 1149 1.3 0.26 0.97 0.20 (week 52) 5 667 2985 2.9 0.68 2.2 0.51 10 1245 5565 5.5 1.3 4.1 0.95 Monkey 52 10 ND ND - - - - (Day 363) 20 ND ND - - - - 30 ND ND - - - - ≥ IPFa 150 228 4410 1 1 NA NA mg BID
and 200 mg BID (NSCLC) and estimated AUC and Cmax values obtained from the Summary of Clinical Pharmacology Studies, where AUC0-12 was 1.82 ng∙h/mL/mg and Cmax was 0.280 ng/mL/mg in IPF patients and AUC0-12 was 2.03 ng∙h/mL/mg and Cmax was 0.282 ng/mL/mg in NSCLC patients; bold and underlined dose was NOAEL; NA = not applicable. 5. Exposures to BIBF 1202 glucuronide in oral repeat dose toxicity and carcinogenicity studies. Species duration time of Dose Cmax ng/mL h ng∙h/mL Exposure ratio# IPF indication Exposure ratio# NSCLC indication on on AUC on on AUC Mouse 13 weeks (Day 87) 10 63.3 197.5 0.28 0.04 0.21 0.03 30 228.5 968.5 1.0 0.22 0.75 0.16 100 1011 5050 4.4 1.2 3.3 0.86 (week 26) 5 16.5 42.7 0.07 0.01 0.05 0.01 15 78.6 399.5 0.34 0.09 0.26 0.07 30 213.5 1291 0.94 0.29 0.70 0.22 Rat 13 weeks (Day 87) 5 780.5 2065 3.4 0.47 2.6 0.35 20 2425 8150 11 1.9 8.0 1.4 60 6865 30000 30 6.8 23 5.1 26 weeks (Day 5 ND ND - - - - 20 ND ND - - - - 80 ND ND - - - - (week 52) 2.5 295.5 1149 1.3 0.26 0.97 0.20 5 667 2985 2.9 0.68 2.2 0.51 10 1245 5565 5.5 1.3 4.1 0.95 Monkey 52 (Day 363) 10 ND ND - - - - 20 ND ND - - - - ≥ 30 ND ND - - - - IPFa 150 mg BID 228 4410 1 1 NA NA Trial
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