Successful integration of nonclinical and clinical findings in interpreting the clinical relevance of rodent neoplasia with a new chemical entity.
Toxicol Pathol
; 43(1): 48-56, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25398756
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canagliflozina
/
Hipoglicemiantes
/
Neoplasias Experimentais
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Toxicol Pathol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos