Brennan – Grant/Research Support: Abbvie, Pfizer, Cubist, Achillion, Sanofi Pasteur, ViiV Healthcare, Glaxo SmithKline Gary Blick – Advisory Committees or Review Panels: viiv healthcare, bms; Grant/
Research Support: abbvie, sangamo biosciences, gilead sciences, viiv healthcare; Speaking and Teaching: viiv healthcare, merck, bms, serono, abbvie, janssen Amit Khatri – Employment: AbbVie, Inc; Patent Held/Filed: AbbVie, Inc; Stock Shareholder: AbbVie, Inc Krystal Gibbons – Employment: AbbVie Yiran Hu – Employment: AbbVie Inc. Linda Fredrick – Employment: AbbVie; Management Position: AbbVie; Stock Shareholder: AbbVie Tami Pilot-Matias – Employment: AbbVie; Stock Shareholder: AbbVie Barbara Da Silva-Tillmann – Employment: AbbVie PLX4032 Barbara H. McGovern – Employment: AbbVie Andrew L. Campbell – Employment: AbbVie; Stock Shareholder: AbbVie Thomas Podsadecki – Employment: AbbVie; Stock Shareholder: AbbVie The following people have nothing this website to disclose: Roger Trinh, Jay Lalezari, Joseph C. Gathe, Chia C. Wang, Richard Elion Background: MK-5172, an inhibitor of the hepatitis C virus (HCV) NS3/4A protease and MK-8742, a HCV NS5A replication complex inhibitor with potent
activity against several HCV genotypes, are being developed as components of an alloral, once-daily direct-acting antiviral regimen for the treatment of chronic HCV. This study evaluated the steady-state plasma pharmacokinetics (PK) of MK-5172 and MK-8742 when coad-ministered in volunteers with end-stage renal disease (ESRD) on hemodialysis (HD) or severe renal impairment (SRI) not on hemodialysis. Methods: This was an open-label, multiple-dose (MD) study to evaluate the PK and
safety of MK-5172 and MK-8742 when coadministered in subjects with ESRD on HD and non-HD days (Part 1, N=8) and subjects with SRI (Part 2, N=8). The PK in Parts 1 and 2 were compared with those in healthy matched control (HMC) subjects who were matched for mean age, BMI, and gender in Parts 1 and 2 (N=8). All subjects received daily Tolmetin doses of 100 mg MK-5172 and 50 mg MK 8742 for 10 days. In Part 1, PK assessments were performed on non-HD Day 9 and HD Day 10 to quantify MK-5172 and MK 8742 removal during HD. Results: Multiple doses of co-administered MK-5172 and MK-8742 were generally well-tolerated in subjects with SRI, with ESRD on HD, and in HMC. The AUC0-24 of MK-5172 and MK-8742 in subjects with ESRD on HD were similar when comparing HD to non-HD days with geometric mean ratios (GMRs) [90% confidence intervals (CI)] of 0.97 [0.87, 1.09] and 1.14 [1.08, 1.21], respectively. Dialysis removed < 0.5% of MK-5172 from plasma and did not remove MK-8742 (0%). The PK of MK-5172 and MK 8742 were similar between subjects with ESRD and HMC with AUC0-24 GMRs [90% CIs] for MK-5172 and MK-8742 of 0.