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Open-Label Hepatic Impairment Study

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PSI-352938

PSI-7977

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring HEPATITIS C, CHRONIC, HCV, hepatic impairment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

PSI-352938 Group A

PSI-352938 Group B

PSI-352938 Group C

PSI-7977 Group A

PSI-7977 Group B

PSI-7977 Group C

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT01497327

First Posted

November 30, 2011

Last Updated

June 7, 2012

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT01497327

Brief Title

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

2. Study Status

Record Verification Date

June 2012

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

Keywords

HEPATITIS C, CHRONIC, HCV, hepatic impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PSI-352938 Group A

Arm Type

Experimental

Arm Description

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

Arm Title

PSI-352938 Group B

Arm Type

Experimental

Arm Description

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

Arm Title

PSI-352938 Group C

Arm Type

Experimental

Arm Description

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

Arm Title

PSI-7977 Group A

Arm Type

Experimental

Arm Description

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

Arm Title

PSI-7977 Group B

Arm Type

Experimental

Arm Description

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

Arm Title

PSI-7977 Group C

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

PSI-352938

Intervention Description

PSI-352938 300mg once daily (QD) for seven days

Intervention Type

Drug

Intervention Name(s)

PSI-7977

Intervention Description

PSI-7977 400mg QD for seven days

Primary Outcome Measure Information:

Title

Pharmacokinetic data derived from plasma samples collected over 7 days

Description

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.

Time Frame

28 time points over Seven Days

Title

Pharmacokinetic comparison with historical data over 7 days of dosing with PSI-7977

Description

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.

Time Frame

Seven Days

Secondary Outcome Measure Information:

Title

Number and severity of adverse events

Description

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.

Time Frame

Seven Days

Title

Viral dynamics/ changes in HCV (ribonucleic acid) RNA

Description

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.

Time Frame

Baseline through follow-up (post-Day 14)

Title

Changes in genotypic or phenotypic measurements

Description

To assess the presence of baseline polymorphisms in viral isolates and development of viral genotypic and phenotypic changes from baseline.

Time Frame

Seven Days

Title

Dosage adjustment in hepatically impaired patients

Description

To provide dosage adjustment guidance for PSI-352938 or PSI-7977 based on the degree of hepatic impairment, if applicable.

Time Frame

Seven days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Facility Information:

City

San Antonio

State/Province

Texas

Country

United States

City

San Juan

ZIP/Postal Code

00927

Country

Puerto Rico

12. IPD Sharing Statement

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Open-Label Hepatic Impairment Study

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