Open-Label Hepatic Impairment Study

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: PSI-352938; Drug: PSI-7977

Study type: Interventional

Funder types: Industry

Identifiers

NCT01497327

P2938-0515

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 6 patient groups

PSI-352938 Group A

Experimental group

Description:

Mild (Child-Pugh Class A; 5-6) hepatic impairment

Treatment:

Drug: PSI-352938

PSI-352938 Group B

Experimental group

Description:

Moderate (Child-Pugh Class B; 7-9) hepatic impairment

Treatment:

Drug: PSI-352938

PSI-352938 Group C

Experimental group

Description:

Severe (Child-Pugh Class C; 10-15) hepatic impairment

Treatment:

Drug: PSI-352938

PSI-7977 Group A

Experimental group

Description:

Mild (Child-Pugh Class A; 5-6) hepatic impairment

Treatment:

Drug: PSI-7977

PSI-7977 Group B

Experimental group

Description:

Moderate (Child-Pugh Class B; 7-9) hepatic impairment

Treatment:

Drug: PSI-7977

PSI-7977 Group C

Experimental group

Description:

Severe (Child-Pugh Class C; 10-15) hepatic impairment

Treatment:

Drug: PSI-7977