About the Clinical Trialsin the PK study in the oral presentation Aryx referenced, two groups were randomized from healthy volunteers of a single oral dose of either equieffective warfarin or ATI received-5923 treatments for ed . ATI-5923, ATI-5900 , infarin and S-warfarin concentrations collected collected AUC, Tmax and T1 / 2) in serial plasma samples over a period of seven days and the PK parameters determined. On day seven, subjects were given FCZ for 14 days, and on day 21, subjects received a second dose of either warfarin or ATI 5923rd FCZ co-administration was continued for 7 days and the PK study was repeated.
An oral presentation entitled ‘The CYP450 inhibitor fluconazole increased plasma concentrations of – and – Warfarin, but not ATI-5923, a novel VKOR inhibitor ‘, described results of a clinical pharmacokinetic study of Aryx. The study compared exposure and elimination rates of ATI-5923 and warfarin in subjects who also were administered the CYP 2C9/3A4 inhibitor fluconazole . The data from this study suggest that exposure and elimination of ATI-5923, the esterase-mediated metabolism is subject, unaffected by FCZ treatment. In contrast, drug levels of warfarin, the CYP450-mediated metabolism is subject dramatically increased FCZ treatment. ‘These data are important because being associated in the clinical setting, DDI-induced increase in warfarin exposure with increased anticoagulant effect and risk of bleeding,’said Peter Milner, President, Research and Development of Aryx. ‘ATI-5923 is designed to have an alternative pathway, so it should inhibit metabolic DDIs with other medicines, or induce CYP450 enzymes avoided. ATI-5923 ‘The poster described results from a 3 – month clinical trial of ATI-5923 in 66 patients with atrial fibrillation, is configuredof genetic variations of CYP2C9 and VKORC1 . It has been found that individuals with CYP2C9 genetic subtype variants are among the most difficult to obtain an appropriate level of anticoagulation during warfarin. The expectation that ATI-5923 has a particularly positive effect on these patients due to ATI-5923 ensures the protection of the CYP pathway is suggested by the results of of this clinical trial. The study data show that patients had more stable control of anticoagulation with ATI-5923 than with prior warfarin therapy, and that patients exhibited with CYP2C9 genetic variation even greater improvements in the control of anticoagulation if them on ATI-5923 than with warfarin. ‘The results of this clinical study reflect what we had hypothesized, based on the unique properties of ATI-5923,’said Dr. ‘Because ATI-5923 is designed to to the metabolism of human and non subject carboxylesterase by CYP2C9, it should not affect on CYP2C9 genetic variations. This genotyping analysis shows us that ATI-5923 is behaving as expected, and that they provide stable control of anticoagulation as a result of its unique metabolism. ‘. Continue reading