Patients tolerated the treatment well without any serious side effects. The treatment course in the remaining 2 patients would finish by
July 2014 and we plan to present our full data including SVR at the 2014 AASLD meeting. Sofosbuvir Treatment in patients RO4929097 with GFR < 30ml/min Disclosures: Cynthia Levy - Consulting: Lumena, Gilead, Evidera Paul Martin - Consulting: Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex; Speaking and Teaching: Roche, BMS, Roche, BMS, Roche, BMS, Roche, BMS The following people have nothing to disclose: Kalyan R. Bhamidimarri, Julio A. Gutierrez, Alla Grigorian, Adam L. Peyton, Christopher O'Brien BACKGROUND: The addition of Telaprevir (TVR) to Pegylated Interferon and Ribavirin for the
treatment of chronic hepatitis C genotype 1 infection has resulted in a significant increase in the rates of sustained virologic response (SVR). However, triple therapy is associated with more side effects, and certain see more groups such as those with cirrhosis are less responsive to therapy. It is unclear whether interindividual pharmacokinetic variability affects treatment outcome. METHODS: TVR pharma-cokinetics was determined in patients undergoing treatment for HCV genotype 1 infection receiving TVR based triple therapy. Patients underwent intensive (rich) PK sampling at steady-state following the administration of 1125mg of Telaprevir bid with food. Samples were collected at 0,1,2,4,6,8,10 and 12 hours post dose, and TVR and its R-diastereomer (VRT-127394) were measured in plasma using a validated HPLC-MS/MS assay. One hundred and sixty eight samples from 21 patients (17 treatment naïve, 4 non-responders; 15 male; 2 cirrhotic) were analysed. The mean age was 41.9+7.9yrs, and mean baseline viral load was log105.66+1.12.
The majority of patients (85%) were IL-28B non-CC. TVR area-under-the-curve-time concentration BCKDHA curves (AUC) were compared between cirrhot-ics and non-cirrhotics, patients achieving a rapid virological response (RVR) vs no RVR, and those with anaemia [Haemoglobin (Hb) < 10 vs >10 g/dl] using an independent samples t-test. The relationship between Telaprevir exposure and Hb decline (by week 2), or liver stiffness were assessed using Pearson correlation. RESULTS: TVR AUC ranged from 17,960-56,009 ng*hr/mL, and mean TVR AUC was lower in patients with cirrhosis (20,323 + 3341 ng*hr/mL) compared to non-cir-rhotics (35,661 + 9888 ng*hr/mL), p = 0.046. There was no significant difference in TVR exposure between RVR and non-RVR patients. Mean TVR AUC was higher in patients with Hb decline below 10g/dl, although this was not statistically significant. Furthermore, there was no significant correlation between TVR AUC and Hb decline by week 2, or liver stiffness. CONCLUSION: TVR AUC is significantly lower in patients with cirrhosis, and this may partly account for the reduced SVR rates reported.
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