Clinical trial NCT01054586: Fosamprenavir in Pts With Hepatic Impairment
Official title: HI FPV Study: Using Observational Cohorts to Monitor Safety of Fosamprenavir in Patients With Mild/Moderate Hepatic Impairment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infection, Human Immunodeficiency Virus
Keywords: antiretroviral therapy
hepatic impairment
HIV
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-01-22
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The source population is from three HIV patient cohorts; ICONA, HEPAVIH and MASTER cohort in Europe. Data from these cohorts are comprised of the clinical records (or a defined subset thereof) of HIV infected patients. The ICONA Foundation study collects data on HIV infected individuals from 67 infectious disease centres across Italy and has been established since 1997. The ICONA cohort only includes patients who are treatment naïve at initial presentation. HEPAVIH is a cohort of HIV-hepatitis co-infected patients, identified from three other ongoing French HIV cohorts: RIBAVIC, SEROCO and AQUITAINE and an additional 12 clinical departments. The MASTER cohort collects data on HIV infected individuals from centres across Italy and includes treatment-experienced and naive patients.

Brief summary: APV10017 was a pharmacokinetic study that evaluated the pharmacokinetics, safety and tolerability of fosamprenavir/ritonavir (FPV/RTV) at reduced doses over 14 days in HIV-infected subjects with mild to moderate hepatic impairment (HI). Based on these data, two new regimens have recently been approved by the EMEA and FDA in these patient groups; FPV 700mg BID/RTV 100mg QD for those with mild HI (Child-Pugh score 4-6) and FPV 450mg BID/RTV 100mg QD for those with moderate HI (Child Pugh score 7-9). The Committee for Medicinal Products for Human Use (CHMP) has requested longer-term safety data among this hepatically impaired HIV-infected population who have received the recently updated FPV/RTV dosing regimens.

An observational cohort study will be conducted using routinely collected data in three European HIV patient cohorts with a high proportion of hepatitis co-infected individuals. Patients who received FPV/RTV will be followed to address the following objectives.

Primary: To assess the safety and tolerability of FPV/RTV-based ART in subjects with mild to moderate hepatic impairment.

Secondary: A). To compare the safety and tolerability of FPV/RTV-based ART in subjects with mild to moderate hepatic impairment when compared to FPV/RTV-based ART in hepatitis B (HBV) or hepatitis C (HCV) co-infected subjects with normal hepatic function. B). To compare the safety and tolerability of FPV/RTV-based ART to lopinavir/ritonavir LPV/RTV-based ART in subjects with mild to moderate hepatic impairment.

Detailed description: Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

Eligibility criteria: Inclusion Criteria:

* HIV infected patients with or without hepatic impairment coinfected with HBV or HCV who started FPV/RTV-based therapy on or after January 1, 2008. The FPV/RTV exposed patients will be stratified into four groups for analysis (see interventions A-D for label/description above), according to their degree of baseline hepatic impairment, which will be defined according to FPV/RTV dose received (and APRI score for interventions A and D). The LPV/RTV intervention group must have started this therapy at approved standard doses on or after January 1, 2008.

Exclusion Criteria:

* Receipt of FPV/RTV or LPV/RTV within the year preceding the baseline visit.

Primary outcomes:
measure: Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables
timeFrame: The incidence of these events was assessed over time during Year 1, censoring participants' follow-up at date of last ALT
measure: Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for APRI-score, and Other Variables
timeFrame: Incidence of these events was assessed over time during Year 1, censoring patients' follow-up at date of last ALT
measure: Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for FIB-score, and Other Variables
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts
timeFrame: Incidence was assessed over time during Year 1
Secondary outcomes:
measure: Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for FIB-score, and Other Variables
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of FPV/RTV- or LPV/RTV Alone by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to Adverse Events Only
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling for APRI-score and Other Variables (See Comments)
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling for FIB-score and Other Variables
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling Current Values of CD4 and Platelet Counts
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of Discontinuation of One or More Drugs in the FPV/RTV- or LPV/RTV Regimen Due to Adverse Events Only
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to the Indicated Adverse Events
timeFrame: Incidence was assessed over time during Year 1
measure: Number of Participants Who Discontinued the Indicated Antiretrovirals for the First Time After Starting FPV/r or LPV/r
timeFrame: Assessed over time during Year 1
measure: Number of Participants With the Indicated Major Reasons for Discontinuing One or More Drugs in the FPV/r or LPV/r Regimen
timeFrame: Assessed over time during Year 1
measure: Number of Participants for Which the Reason for Discontinuation of One or More Drugs in the FPV/RTV or LPV/RTV Regimen Was Due to Adverse Events Only
timeFrame: The incidence of these events was assessed over time during Year 1
measure: Incidence Rates Per 100 Person-years of Follow-up (PYFU) of Study Main Outcome Measures
timeFrame: Incidence of these events was assessed over time during Year 1
Other outcomes:
measure: Median Length of Participant Follow-up and Length of Time on Antiretroviral Therapy (ART) at Baseline
timeFrame: Baseline
measure: Cluster of Differentiation (CD4) Count at Baseline
timeFrame: Baseline
measure: Median Aspartate Aminotransferase (AST)-Platelet Ratio Index (APRI) Score at Baseline
timeFrame: Baseline
measure: Median FIB (a Model of End-stage Liver Disease) Score at Baseline
timeFrame: Baseline
measure: Median Model of End-stage Liver Disease (MELD) Score at Baseline
timeFrame: Baseline
measure: Median ALT and AST Scores at Baseline
timeFrame: Baseline
measure: Median Blood Platelet Count at Baseline
timeFrame: Baseline
measure: Median Bilirubin Level at Baseline
timeFrame: Baseline
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: