Open-Label Hepatic Impairment Study

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497327
• Other study ID #: P2938-0515
• Status: Completed
• Phase: Phase 1
• First received: November 30, 2011
• Last updated: June 7, 2012
• Start date: July 2011
• Est. completion date: January 2012

Study information

• Verified date: June 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C
• Liver Diseases

Intervention

Drug:
• PSI-352938
PSI-352938 300mg once daily (QD) for seven days
• PSI-7977
PSI-7977 400mg QD for seven days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	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)	Yes
Secondary	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	Yes
Secondary	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	No