Relative exposure - ombitasvir Relative exposure ratios are calculated based on clinical AUC0-24h values that were determined from a study in healthy volunteers (Study No. R&D/14/0050). Exposures attained in the pivotal toxicity studies were adequate multiples of clinical plasma levels. Table 5: Relative exposure to ombitasvir in repeat-dose toxicity and carcinogenicity studies - ombitasvir Species Study Sex Dose duration h ratio# Mouse [Tg(Hras)] 26 week 2.5 2.67 2 male Study No. 10 10.7 7.5 R&D/12/574 150 36.6 26 5 2.98 2.1 female 20 12.4 8.7 150 37 26 Mouse 6 month 5 3.57 2.5 male [CD-1] [Pivotal 20 10.5 7.4 toxicity] 200 40.8 29 Study No. R&D/11/561 Sampling 10 3.38 2.4 female day: 182 40 17.9 12.6 200 32.1 23 Rat [SD] 3 month male/ 10 10.7/9.2 7.5/6.5 female Study No. [Pivotal 30 14.4/18 R&D/10/1472 toxicity] 300 16/25 Sampling day: 91 Dog [Beagle] 6 male/ 4 8.5/6 6/4.2 female Study No. [Pivotal 20 54/41.5 38/29 R&D/10/1371 toxicity] Sampling 100 90/77 day: 189 Study Steady state 25 1.42 – – R&D/14/0500 mg/day
Relative exposure - ombitasvir Relative exposure ratios are calculated based on clinical AUC0-24h values that were determined from a study in healthy volunteers (Study No. R&D/14/0050). Exposures attained in the pivotal toxicity studies were adequate multiples of clinical plasma levels. Table 5: Relative exposure to ombitasvir in repeat-dose toxicity and carcinogenicity studies - ombitasvir Species Study duration Sex Dose h ratio# Mouse [Tg(Hras)] Study No. R&D/12/574 26 week male 2.5 2.67 2 10 10.7 7.5 150 36.6 26 female 5 2.98 2.1 20 12.4 8.7 150 37 26 Mouse [CD-1] Study No. R&D/11/561 6 month [Pivotal toxicity] Sampling day: 182 male 5 3.57 2.5 20 10.5 7.4 200 40.8 29 female 10 3.38 2.4 40 17.9 12.6 200 32.1 23 Rat [SD] Study No. R&D/10/1472 3 month [Pivotal toxicity] Sampling day: 91 male/ female 10 10.7/9.2 7.5/6.5 30 14.4/18 300 16/25 Dog [Beagle] Study No. R&D/10/1371 6 [Pivotal toxicity] Sampling day: 189 male/ female 4 8.5/6 6/4.2 20 54/41.5 38/29 100 90/77 Study R&D/14/0500 Steady state – 25 mg/day 1.42 –
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