Hepatitis C
Conditions
Keywords
HEPATITIS C, CHRONIC, HCV, hepatic impairment
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.
Interventions
DRUGPSI-352938
PSI-352938 300mg once daily (QD) for seven days
DRUGPSI-7977
PSI-7977 400mg QD for seven days
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Puerto Rico, United States
Outcome results
None listed