1201 NO CLINICALLY SIGNIFICANT PHARMACOKINETIC INTERACTION BETWEEN SOVAPREVIR AND ACH-3102 IN HEALTHY VOLUNTEERS

Background: This study evaluated the potential for a pharmacokinetic (PK) interaction when sovaprevir (formerly ACH-1625), a novel NS3 HCV protease inhibitor, and ACH-3102, a second generation NS5A inhibitor, were coadministered. Sovaprevir was administered as an oral tablet, while ACH-3102 was administered as an oral liquid-filled capsule (LFC). This study also investigated whether a PK interaction existed between sovaprevir and the excipients of the ACH-3102 LFC. Methods: Twenty-four (24) healthy volunteers were divided into 4 groups. Subjects in Groups 1 (n=6) and 2 (n=6) each received a single 300 mg dose of sovaprevir with a standard meal on Day 1, followed by a washout period (Days 2 to 4), and then a single 300 mg dose of sovaprevir, co-administered with either 300 mg ACH-3102 LFC (Group 1) or placebo (Group 2) while fed a standard meal (Day 5). Subjects in Groups 3 (n=6) and 4 (n=6) each received a single 300 mg dose of sovaprevir while fasted on Day 1, followed by a washout period (Days 2 to4), and then a single 300 mg dose of sovaprevir co-administered with either 300 mg ACH3102 LFC (Group 3) or placebo (Group 4) while fasted (Day 5). Results: For sovaprevir, the respective mean Day 5/Day 1 ratios (coadministered with ACH- 3102 versus dosed alone) of Cmax, AUC(0-24) and AUC(O-∞) were 0.96, 1.05 and 1.05 when fed, and 0.89, 0.77 and 0.77 when fasted. Similarly, for sovaprevir, the respective mean Day 5/Day 1 ratios (co-administered with placebo for ACH-3102 LFC versus dosed alone) of Cmax, AUC(0-24) and AUC(O-∞) were 0.84, 0.91 and 0.90 when fed, and 1.17, 1.12 and 1.08 when fasted. Mean observed Cmax, AUC(0-24) and AUC(0-192) of ACH-3102 when coadministered with sovaprevir were all within approximately 25% of values from previous studies. Conclusions: No clinically significant change was observed in the PK of either sovaprevir or ACH-3102 when co-administered in either the fed or fasted state. No clinically significant change was observed in the PK of sovaprevir when coadministered with the excipients of the ACH-3102 LFC. Co-administration of the two agents was safe and well-tolerated.