Conclusions Severe renal impairment had minimal impact on the PK of ASV; data suggest no dose adjustment is needed for ASV in subjects with any level of renal impairment. Disclosures: Tushar Garimella – Employment: Bristol Myers-Squibb; Stock Shareholder: Abbvie Bing He – Employment: Bristol-Myyers Squibb Wen-Lin Luo – Employment: BMS Elizabeth Colston – Employment: Bristol-Myers Squibb Kurt Zhu – Employment: Bristol-Myers Squibb Thomas
C. Marbury- Employment: Orlando Clinical Research Center Timothy Eley- Employment: Bristol-Myers Squibb; Stock Shareholder: Bristol-Myers Squibb The following people have nothing to disclose: Hamza Kandoussi, Harry W. Alcorn, William B. Smith Background: MK-5172, a potent, once-daily competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease, and daclatasvir (DCV), an HCV NS5A replication complex www.selleckchem.com/products/Fulvestrant.html inhibitor with pan-genotypic
activity in vitro, are being developed for the treatment of chronic HCV infection. The aim of the present study was to evaluate Decitabine potential pharmacokinetic interactions as well as safety and tolerability of MK-5172 and daclatasvir co-administration in healthy subjects. Methods: This was a single-center, open-label, fixed-sequence, multiple-dose study in 14 healthy adult male and female volunteers, ages 19-49 years. Since MK-5172 in HCV-infected patients demonstrates ∼2-fold higher exposure compared to healthy subjects, a 200 mg dose of MK-5172 in healthy subjects was used in this study to match the exposure of a 100 mg dose (the intended clinical dose) in HCV-infected patients.
In Period 1, subjects received oral doses of 60 mg daclatasvir once daily on Days 1 to 7. Following a 4 day washout, subjects received oral doses of 200 mg MK-5172 once daily on Days 1 to 7 in Period 2. In Period 3, which commenced immediately after Period 2, subjects were co-administered once daily oral doses of 200 mg MK-5172 and 60 mg daclatasvir on Days 1 to 8. Plasma pharmacokinetic samples were obtained for daclatasvir on Day 7 in Period 1 and Day 8 in MCE Period 3, as well as for MK-5172 on Day 7 in Period 2 and Day 8 in Period 3. Safety assessments included electrocardiograms, vital signs, clinical laboratory tests, physical examination, and adverse event monitoring. Results: Co-administration of MK-51 72 with daclatasvir was safe and well-tolerated. Multiple oral doses of MK-51 72 did not meaningfully change the steady-state AUC0-τ, Cmax, or C24h of daclatasvir with MK-5172+DCV/DCV geometric mean ratios (GMRs) [90% confidence intervals (CIs)] of 1.02 [0.93, 1.11], 0.80 [0.74, 0.86], and 1.23 [1.09, 1.38], respectively. Multiple oral doses of daclatasvir did not meaningfully change the steady-state AUC0-τ, Cmax, or C24h of MK-5172 with MK-5172+DCV/MK-5172 GMRs [90% CIs] of 1.12 [0.87, 1.44], 1.11 [0.77, 1.60], and 1.04 [0.97, 1.12], respectively. Conclusions: Co-administration of MK-5172 and daclatasvir in healthy volunteers did not result in clinically significant drug-drug interactions.