Open-Label Hepatic Impairment Study - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C	Drug: PSI-352938 Drug: PSI-7977	Phase 1

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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Pharmacokinetic data derived from plasma samples collected over 7 days [ Time Frame: 28 time points over Seven Days ] [ Designated as safety issue: No ]
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 [ Time Frame: Seven Days ] [ Designated as safety issue: No ]
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 Outcome Measures:

Number and severity of adverse events [ Time Frame: Seven Days ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline through follow-up (post-Day 14) ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Seven Days ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Seven days ] [ Designated as safety issue: No ]
To provide dosage adjustment guidance for PSI-352938 or PSI-7977 based on the degree of hepatic impairment, if applicable.

Enrollment:	24
Study Start Date:	July 2011
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01497327

Locations

United States, Texas

San Antonio, Texas, United States
Puerto Rico

San Juan, Puerto Rico, 00927

Sponsors and Collaborators

Gilead Sciences

More Information

No publications provided

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01497327 History of Changes
Other Study ID Numbers:	P2938-0515
Study First Received:	November 30, 2011
Last Updated:	June 7, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

HEPATITIS C, CHRONIC
HCV
hepatic impairment

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human

Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on May 23, 2013