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Open-Label Hepatic Impairment Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01497327
Recruitment Status : Completed
First Posted : December 22, 2011
Last Update Posted : June 8, 2012
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 30, 2011
First Posted Date  ICMJE December 22, 2011
Last Update Posted Date June 8, 2012
Study Start Date  ICMJE July 2011
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2011)
  • Pharmacokinetic data derived from plasma samples collected over 7 days [ Time Frame: 28 time points over Seven 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 [ Time Frame: Seven Days ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2011)
  • Number and severity of adverse events [ Time Frame: Seven Days ]
    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) ]
    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 ]
    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 ]
    To provide dosage adjustment guidance for PSI-352938 or PSI-7977 based on the degree of hepatic impairment, if applicable.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-Label Hepatic Impairment Study
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: PSI-352938
    PSI-352938 300mg once daily (QD) for seven days
  • Drug: PSI-7977
    PSI-7977 400mg QD for seven days
Study Arms  ICMJE
  • Experimental: PSI-352938 Group A
    Mild (Child-Pugh Class A; 5-6) hepatic impairment
    Intervention: Drug: PSI-352938
  • Experimental: PSI-352938 Group B
    Moderate (Child-Pugh Class B; 7-9) hepatic impairment
    Intervention: Drug: PSI-352938
  • Experimental: PSI-352938 Group C
    Severe (Child-Pugh Class C; 10-15) hepatic impairment
    Intervention: Drug: PSI-352938
  • Experimental: PSI-7977 Group A
    Mild (Child-Pugh Class A; 5-6) hepatic impairment
    Intervention: Drug: PSI-7977
  • Experimental: PSI-7977 Group B
    Moderate (Child-Pugh Class B; 7-9) hepatic impairment
    Intervention: Drug: PSI-7977
  • Experimental: PSI-7977 Group C
    Severe (Child-Pugh Class C; 10-15) hepatic impairment
    Intervention: Drug: PSI-7977
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 7, 2012)
24
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2011)
48
Actual Study Completion Date  ICMJE January 2012
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01497327
Other Study ID Numbers  ICMJE P2938-0515
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Gilead Sciences
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP