Open-Label Hepatic Impairment Study
- Registration Number
- NCT01497327
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Hepatic impaired Males or females of non-childbearing potential aged > 18 years with Chronic HCV-infection
- Naïve to all direct acting anti-viral (DAA) treatments for chronic HCV infection.
- Documented Cirrhosis
- Prior PEG/RBV null responders.
- Unstable cardiac disease, recent Myocardial infarction, or family history of QTc prolongation or unexplained cardiac arrest.
- Positive test at Screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti-human immunodeficiency virus (HIV) Ab.
- History of clinically significant medical condition associated with other chronic liver disease
- Any current signs or symptoms of severe hepatic encephalopathy
- History of gastric or esophageal variceal bleeding in which varices have not been adequately treated with medication and surgical procedures
- Prior placement of a portosystemic shunt
- History of hepatorenal, or hepatopulmonary syndrome.
- Active spontaneous bacterial peritonitis.
- Use of medications associated with QT prolongation within 28 days prior to dosing.
- Current Hypotension
- History of Torsades de Pointes, evidence of an active or suspected cancer, or a history of malignancy, Abnormal hematological and biochemical parameters
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PSI-7977 Group A PSI-7977 Mild (Child-Pugh Class A; 5-6) hepatic impairment PSI-7977 Group B PSI-7977 Moderate (Child-Pugh Class B; 7-9) hepatic impairment PSI-7977 Group C PSI-7977 Severe (Child-Pugh Class C; 10-15) hepatic impairment PSI-352938 Group B PSI-352938 Moderate (Child-Pugh Class B; 7-9) hepatic impairment PSI-352938 Group A PSI-352938 Mild (Child-Pugh Class A; 5-6) hepatic impairment PSI-352938 Group C PSI-352938 Severe (Child-Pugh Class C; 10-15) hepatic impairment
- Primary Outcome Measures
Name Time Method Pharmacokinetic data derived from plasma samples collected over 7 days 28 time points over Seven 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.
Pharmacokinetic comparison with historical data over 7 days of dosing with PSI-7977 Seven Days 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.
- Secondary Outcome Measures
Name Time Method Viral dynamics/ changes in HCV (ribonucleic acid) RNA Baseline through follow-up (post-Day 14) 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.
Dosage adjustment in hepatically impaired patients Seven days To provide dosage adjustment guidance for PSI-352938 or PSI-7977 based on the degree of hepatic impairment, if applicable.
Number and severity of adverse events Seven Days 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.
Changes in genotypic or phenotypic measurements Seven Days To assess the presence of baseline polymorphisms in viral isolates and development of viral genotypic and phenotypic changes from baseline.