Open-Label Hepatic Impairment Study

NCT01497327 | Completed Phase 1

• 1 other identifier: P2938-0515
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hepatitis C

Keywords

HEPATITIS C, CHRONIC; HCV; hepatic impairment

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Number and severity of adverse events

  Seven Days

• Viral dynamics/ changes in HCV (ribonucleic acid) RNA

  Baseline through follow-up (post-Day 14)

• Changes in genotypic or phenotypic measurements

  Seven Days

• Dosage adjustment in hepatically impaired patients

  Seven days

Study Arms (6)

PSI-352938 Group A

EXPERIMENTAL

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

Drug: PSI-352938

PSI-352938 Group B

EXPERIMENTAL

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

Drug: PSI-352938

PSI-352938 Group C

EXPERIMENTAL

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

Drug: PSI-352938

PSI-7977 Group A

EXPERIMENTAL

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

Drug: PSI-7977

PSI-7977 Group B

EXPERIMENTAL

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

Drug: PSI-7977

PSI-7977 Group C

EXPERIMENTAL

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

Drug: PSI-7977

Interventions

PSI-352938 DRUG

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

PSI-352938 Group A; PSI-352938 Group B; PSI-352938 Group C

PSI-7977 DRUG

PSI-7977 400mg QD for seven days

PSI-7977 Group A; PSI-7977 Group B; PSI-7977 Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (2)

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

San Juan, Puerto Rico, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Hepatitis C; Hepatitis C, Chronic

Interventions

PSI 352938; Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2011
• First Posted: December 22, 2011
• Study Start: July 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: June 8, 2012

Record last verified: 2012-06

Locations

US (1); PR (1)