Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

SOTRASTAURIN, (AEB071), PROLONGS KIDNEY ALLOGRAFT SURVIVAL ALONE OR IN COMBINATION WITH CYCLOSPORINE IN NON-HUMAN PRIMATES

Bigaud, Marc and Wieczorek, Grazyna and Menninger, Klaus and Barbet, Irène and Jean, Christian and Beerli, Christian and Audet, Maxime and Blancher, Antoine and Heusser, Christoph and Morris, Randall and Wagner, Juergen (2012) SOTRASTAURIN, (AEB071), PROLONGS KIDNEY ALLOGRAFT SURVIVAL ALONE OR IN COMBINATION WITH CYCLOSPORINE IN NON-HUMAN PRIMATES. Transplantation, 93 (2). pp. 156-164. ISSN 0041-1337

Abstract

Background: Sotrastaurin (STN), a novel oral protein kinase C inhibitor, blocks early T-cell activation. Its immunosuppressive effect was assessed in a non-human primate (NHP) model of kidney transplantation (Tx).
Methods: Cynomolgus monkeys received life-supporting kidney allografts and daily oral treatments with STN or cyclosporine A (CsA) alone or in combination.
Results: STN alone at 50 mg/kg QD prolonged graft survival up to predefined end point of 29 days (n=2). When STN was given at 25 mg/kg BID, median survival time (MST) of grafts was 27 days (n=4). STN or CsA monotherapy (both at 20 mg/kg/day) did not increase MST (6 and 7 days, with n=2 and 5, respectively), whereas when given as combination (20/20 mg/kg/d) prolonged MST by >100 days (n=5). The MSTs for STN/CsA combinations at 7/20 and 2/20 mg/kg/day were >100 days (n=3) and 22 days (n=2), respectively. In all of these combination groups, the STN trough levels (C0) were dose-related (30–182, 7–41 and 3–5 ng/mL, respectively), while the CsA-C0 levels remained unchanged, suggesting that the potentiation of CsA efficacy by STN was not due to PK interactions. This was confirmed by separate PK studies in normal NHP.
Conclusion: STN appears to be an efficacious immunosuppressive agent for the prevention of organ rejection in NHP. This supports its current development in clinical transplantation.

Item Type: Article
Related URLs:
Keywords: Kidney, Non-human primates, Sotrastaurin, Transplantation
Related URLs:
Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/3729

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.