This study will be conducted in Hepatitis C positive patients to determine whether the pharmacodynamic effects of PSI-7977 or PSI-352938 are similar to HCV-infected patients with normal hepatic function, which may allow inclusion of patients with cirrhosis and varying degrees of hepatic dysfunction in future clinical studies.
This study is designed per the Food and Drug Administration (FDA) guidance for patients with impaired hepatic function to assess the influence of hepatic impairment on the PK and pharmacodynamics (PD) of PSI-7977 and PSI-352938 This study will be conducted in Hepatitis C positive patients to ascertain whether the PD effects of PSI-7977 or PSI-352938 are similar to HCV-infected patients with normal hepatic function, which may allow inclusion of patients with cirrhosis and varying degrees of hepatic dysfunction in future clinical studies. Data from subjects who participated in the P2938-0212 study (PSI-352938 MAD) will be used as the control group. These subjects were documented non-cirrhotic subjects with normal hepatic function. Hepatitis C Virus (HCV) Genotypes 1-6 will be enrolled in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
PSI-352938 300mg once daily (QD) for seven days
PSI-7977 400mg QD for seven days
Unnamed facility
San Antonio, Texas, United States
Unnamed facility
San Juan, Puerto Rico, Puerto Rico
Pharmacokinetic data derived from plasma samples collected over 7 days
To characterize the pharmacokinetics (PK) of PSI-352938 over 7 days of dosing with PSI-352938 in HCV-infected patients with varying degrees of hepatic impairment compared to historical PK data.
Time frame: 28 time points over Seven Days
Pharmacokinetic comparison with historical data over 7 days of dosing with PSI-7977
To characterize the PK of PSI-7977 and metabolites over 7 days of dosing with PSI-7977 in HCV-infected patients with varying degrees of hepatic impairment compared to historical PK data.
Time frame: Seven Days
Number and severity of adverse events
To assess the safety and tolerability of 7 days of dosing of PSI-352938 or PSI-7977 in HCV infected patients with varying degrees of hepatic impairment.
Time frame: Seven Days
Viral dynamics/ changes in HCV (ribonucleic acid) RNA
To evaluate the viral dynamics as measured by changes in the HCV RNA in HCV-infected patients with varying degrees of hepatic impairment after 7 days of dosing with PSI-352938 or PSI-7977.
Time frame: Baseline through follow-up (post-Day 14)
Changes in genotypic or phenotypic measurements
To assess the presence of baseline polymorphisms in viral isolates and development of viral genotypic and phenotypic changes from baseline.
Time frame: Seven Days
Dosage adjustment in hepatically impaired patients
To provide dosage adjustment guidance for PSI-352938 or PSI-7977 based on the degree of hepatic impairment, if applicable.
Time frame: Seven days
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