P12: Miravirsen does not interact with telaprevir

Abstract

BACKGROUND: Miravirsen sodium is a b-D-oxy-Locked Nucleic Acid (LNA)-modified phosphorothioate anti-sense oligonucleotide inhibitor of the liver-expressed microRNA122 (miR-122). Miravirsen reduces HCV RNA levels indirectly, by targeting the critical host factor miR-122 rather than by directly targeting the virus. Prior clinical and nonclinical studies have demonstrated miravirsen activity against all HCV genotypes (GT) and long-lasting suppression of HCV viremia without evidence of viral resistance. Miravirsen is not metabolized by CYP450 enzymes suggesting it has a low propensity for drug-drug interactions. METHOD: An open-label drug interaction study was performed in healthy subjects to assess the effect of miravirsen on telaprevir plasma PK. Five subjects received telaprevir every day during a week (Days 1–7). The subjects subsequently received five single doses of miravirsen (7 mg/kg, on Days 8, 15, 22, 29 and 36). In the period from Day 30 to Day 36, the subjects once more received telaprevir daily. The plasma PK for telaprevir were followed on Days 1, 7, 30 and 36 and those for miravirsen on Days 15 and 36. The plasma PK of telaprevir before and after miravirsen treatment were compared, as well as those after a singleand multiple dosing with telaprevir. The effect of telaprevir on miravirsen plasma PK was also studied. RESULTS: The study showed that repeated dosing with miravirsen (five doses over 29 days) had no effect on exposure (expressed as AUC values) of the subsequently administered telaprevir, Day 36 versus Day 7 (A). Neither had repeated dosing with telaprevir during 1 week any effect on subsequently administered miravirsen, Day 36 versus Day 15 (B). There was no statistically or clinically significant difference on systemic exposure of telaprevir at steady state or miravirsen when these compounds were co administered as compared with administration alone. CONCLUSION: There is no meaningful drug interaction between miravirsen and telaprevir upon co-administration in healthy subjects. P13 Plasma TIMP-1/MMP-2 ratio dynamics in patients with chronic hepatitis C treated with PegIFN and ribavirin H Fota-Markowska, E Kobylecka and A Przybyla Medical University of Lublin, Lublin, Poland