Appendix 8 Summary of Important Risks New or updated risks are Non-clinical data Clinical data Actions denoted with an asterisk. Risk Hepatotoxicity* Rat study KR-102: 2 With frequent Routine monitoring of 8 rats in the monitoring of ALT, in ongoing Phase III highest dose group AST, alkaline study (301): ALT, (60 mg/kg/d) phosphatase, and AST, alkaline developed bilirubin in the phosphatase, and centrilobular Phase I and II trials, bilirubin monitored necrosis. At lower no consistent at baseline, Weeks doses, no rats had pattern of laboratory 1, 4, 12, and 48. evidence of abnormalities hepatotoxicity. emerged suggestive No hepatotoxicity of liver injury. seen in rabbits at doses < 60 mg/kg/d.
Appendix 8 Summary of Important Risks New or updated risks are denoted with an asterisk. Risk Non-clinical data Clinical data Actions Hepatotoxicity* Rat study KR-102: 2 of 8 rats in the highest dose group (60 mg/kg/d) developed centrilobular necrosis. At lower doses, no rats had evidence of hepatotoxicity. No hepatotoxicity seen in rabbits at doses < 60 mg/kg/d. With frequent monitoring of ALT, AST, alkaline phosphatase, and bilirubin in the Phase I and II trials, no consistent pattern of laboratory abnormalities emerged suggestive of liver injury. Routine monitoring in ongoing Phase III study (301): ALT, AST, alkaline phosphatase, and bilirubin monitored at baseline, Weeks 1, 4, 12, and 48.
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