6 BMS-790052 was previously found to be safe and well tolerated when administered in healthy non-HCV-infected subjects at doses up Enzalutamide order to 200 mg as a single dose, and up to 60 mg once daily for 14 days. In a previous trial of patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 hours postdose. This response was sustained for an additional 120 hours in two patients infected with genotype 1b virus.6 Here we report the results of the first placebo-controlled, multiple ascending dose clinical study
to evaluate the antiviral activity, resistance profile, pharmacokinetics (PK), safety, and tolerability BMN 673 mw of an HCV NS5A replication complex inhibitor, BMS-790052, in patients chronically infected with HCV genotype 1. AE, adverse event; AUC, area under the plasma concentration time curve; AUC(TAU), AUC over 12-hour dosing interval for 30 mg twice daily; Cmin, minimum observed plasma concentration; Cmax, maximum observed plasma concentration; Ctrough, trough concentrations; CLT/F, apparent total body clearance;
CV, coefficient of variation; DAA, direct-acting antiviral; ECG, electrocardiogram; HCV, hepatitis C virus; ISG, interferon-stimulated gene; NS5A, nonstructural protein 5A; PCR, polymerase chain reaction; PEG-IFN, pegylated interferon; PK, pharmacokinetics; daily; RBV, ribavirin; Tmax, time of maximum observed plasma concentration; T1/2, half life. This study was a double-blind, placebo-controlled, sequential panel, multiple ascending dose study. Six dose regimens of BMS-790052 in HCV genotype 1-infected patients were evaluated (1 mg once daily, 10 mg once daily, 30 mg once or twice daily, 60 mg once daily, and 100 mg once daily) (ClinicalTrials.gov number,
NCT00663208). Five patients in each panel were randomized to receive a 14-day course of orally administered BMS-790052 or placebo in a ratio of 4:1. Patients were admitted to one of eight clinical facilities in the United States between May 2008 and June 2009, and required to remain in-house from day −1 (screening day) to day 2, and from day 13 to day 15. Patients were permitted 上海皓元 to be furloughed from the clinical facility from day 3 to day 12 and from day 16 to study discharge, which occurred at approximately day 182 for patients receiving active drug, following completion of additional blood sampling for analysis of HCV RNA and genomic substitutions. Patients treated with placebo were not required to return for follow-up visits beyond day 28. The majority of patients were treated as inpatients from day −1 to day 15. BMS-790052 or placebo was administered under fasting conditions. No intrapatient dose escalation was allowed.