Open-Label Hepatic Impairment Study

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: PSI-352938; Drug: PSI-7977

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
• United States
  • Texas
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PSI-352938 Group A; Mild (Child-Pugh Class A; 5-6) hepatic impairment	Drug: PSI-352938; PSI-352938 300mg once daily (QD) for seven days
Experimental: PSI-352938 Group B; Moderate (Child-Pugh Class B; 7-9) hepatic impairment	Drug: PSI-352938; PSI-352938 300mg once daily (QD) for seven days
Experimental: PSI-352938 Group C; Severe (Child-Pugh Class C; 10-15) hepatic impairment	Drug: PSI-352938; PSI-352938 300mg once daily (QD) for seven days
Experimental: PSI-7977 Group A; Mild (Child-Pugh Class A; 5-6) hepatic impairment	Drug: PSI-7977; PSI-7977 400mg QD for seven days
Experimental: PSI-7977 Group B; Moderate (Child-Pugh Class B; 7-9) hepatic impairment	Drug: PSI-7977; PSI-7977 400mg QD for seven days
Experimental: PSI-7977 Group C; Severe (Child-Pugh Class C; 10-15) hepatic impairment	Drug: PSI-7977; PSI-7977 400mg QD for seven days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Seven Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Seven days

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Estimate): June 8, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: HCV; hepatic impairment; HEPATITIS C, CHRONIC
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: P2938-0515