1. Successful Integration of Nonclinical and Clinical Findings in Interpreting the Clinical Relevance of Rodent Neoplasia with a New Chemical Entity.
- Author
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Johnson, Mark D., Louden, Calvert, De Jonghe, Sandra, Ways, Kirk, Mamidi, Rao N. V. S., and Proctor, James
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SODIUM-glucose cotransporters , *CANAGLIFLOZIN , *CARCINOGENICITY , *ANIMAL models in research , *TYPE 2 diabetes treatment , *PHEOCHROMOCYTOMA , *LEYDIG cell tumors - Abstract
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been developed for the treatment of adults with type 2 diabetes mellitus (T2DM). During the phase 3 program, treatment-related pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. Treatment-related tumors were not seen in the 2-year mouse study. A cross-functional, mechanism-based approach was undertaken to determine whether the mechanisms responsible for tumorigenesis in the rat were of relevance to humans. Based on findings from nonclinical and clinical studies, the treatment-related tumors observed in rats were not deemed to be of clinical relevance. Here, we describe the scientific and regulatory journey from learning of the 2-year rat study findings to the approval of canagliflozin for the treatment of T2DM. [ABSTRACT FROM PUBLISHER]
- Published
- 2015
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