1131 ACTIVE INJECTION DRUG USER'S CAN BE SUCCESSFULLY TREATED FOR HCV AND SIGNIFICANTLY REDUCE ILLICIT DRUG USE POST TREATMENT: REAL LIFE COHORT OF 152 PATIENTS

Abstract

the primary systemic metabolite of PSI-7977, PSI-6206, were determined following the first and 7th dose of PSI-7977. HCVRNA and safety were monitored throughout the study. All data were compared to that obtained from non-cirrhotic HCV-infected subjects receiving 7 days of PSI-7977 400mg QD in the NUCLEAR study (Cohort 3). Results: Nine moderately hepatic-impaired HCV-infected subjects were enrolled. One subject withdrew study consent without explanation or reported AEs and was replaced. Two AEs of nausea and diarrhea (single instances) were reported, with no severe AEs or SAEs reported. Geometric least squares mean ratios (90% CIs) for PSI-6206 Day 7 Cmax and AUCtau in subjects with moderate hepatic impairment relative to non-cirrhotic subjects were 0.94 (0.67, 1.31) and 1.18 (0.84, 1.64), respectively. Median baseline HCVRNA was 5.8 log10 IU/mL, and at Day 7, a median reduction in HCVRNA of 3.7 log10 IU/mL was observed (range 2.8–4.1). One subject achieved HCVRNA <LOD (15 IU/mL). Following a review of the PSI-7977 safety profile in subjects with moderate hepatic impairment, HCV-infected subjects with severe hepatic impairment (Child-Pugh C) will be enrolled, with data available at the time of the presentation. Conclusions: HCV-infected subjects with moderate hepatic impairment were administered PSI-7977 400mg QD for 7 days; PSI-7977 was generally well-tolerated and resulted in similar systemic exposure to PSI-6206 as non-cirrhotic subjects. Significant declines in HCVRNA were observed in all subjects over 7 days of dosing, confirming the intrahepatic activity of PSI-7977 in these considerably more advanced individuals. Viral kinetics were less profound than those observed in less advanced patients, potentially related to absorption and hepatic blood flow (shunting). Additional studies of individuals with advanced cirrhosis will be conducted to determine optimal duration of therapy in these patients.