Clinical trial NCT01497327: Open-Label Hepatic Impairment Study
Official title: An Open-Label Study to Characterize the Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of PSI-7977 or PSI-352938 in HCV-infected Subjects With Varying Degrees of Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Keywords: HEPATITIS C, CHRONIC
HCV
hepatic impairment
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-12-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic data derived from plasma samples collected over 7 days
timeFrame: 28 time points over Seven Days
measure: Pharmacokinetic comparison with historical data over 7 days of dosing with PSI-7977
timeFrame: Seven Days
Secondary outcomes:
measure: Number and severity of adverse events
timeFrame: Seven Days
measure: Viral dynamics/ changes in HCV (ribonucleic acid) RNA
timeFrame: Baseline through follow-up (post-Day 14)
measure: Changes in genotypic or phenotypic measurements
timeFrame: Seven Days
measure: Dosage adjustment in hepatically impaired patients
timeFrame: Seven days
Other outcomes:
Locations:
city: San Antonio
country: United States
state: Texas
city: San Juan
country: Puerto Rico
Study officials:
References: