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.

Trial Health

100

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

167

participants targeted

Target at P50-P75 for all trials

Timeline

Completed

Started Jan 2009

Typical duration for all trials

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.2 years study duration

Study Start

First participant enrolled

January 1, 2009

Completed

1.1 years until next milestone

First Submitted

Initial submission to the registry

January 21, 2010

Completed

1 day until next milestone

First Posted

Study publicly available on registry

January 22, 2010

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

June 28, 2011

Completed

8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed

Last Updated

May 7, 2013

Status Verified

April 1, 2013

Enrollment Period

3.2 years

First QC Date

January 21, 2010

Results QC Date

January 14, 2011

Last Update Submit

May 2, 2013

Conditions

Infection, Human Immunodeficiency Virus

Keywords

antiretroviral therapyhepatic impairmentHIV

Outcome Measures

Primary Outcomes (4)

Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables
An elevation in ALT is defined as a single value \>200 IU/I.
The incidence of these events was assessed over time during Year 1, censoring participants' follow-up at date of last ALT
Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for APRI-score, and Other Variables
An elevation in ALT is defined as a single value \>200 IU/I.
Incidence of these events was assessed over time during Year 1, censoring patients' follow-up at date of last ALT
Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for FIB-score, and Other Variables
An elevation in ALT is defined as a single value \>200 IU/I.
Incidence was assessed over time during Year 1
Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts
An elevation in ALT is defined as a single value \>200 IU/I.
Incidence was assessed over time during Year 1

Secondary Outcomes (13)

Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables
Incidence was assessed over time during Year 1
Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for FIB-score, and Other Variables
Incidence was assessed over time during Year 1
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
Incidence was assessed over time during Year 1
Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to Adverse Events Only
Incidence was assessed over time during Year 1
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)
Incidence was assessed over time during Year 1
+8 more secondary outcomes

Other Outcomes (8)

Median Length of Participant Follow-up and Length of Time on Antiretroviral Therapy (ART) at Baseline
Baseline
Cluster of Differentiation (CD4) Count at Baseline
Baseline
Median Aspartate Aminotransferase (AST)-Platelet Ratio Index (APRI) Score at Baseline
Baseline
+5 more other outcomes

Study Arms (1)

HIV pts w/ HBV or HCV, w/ or w/o mild to moderate HI

Patients with HIV coinfected with HBV or HCV with or without mild to moderate HI who are enrolled in one of the participating HIV patient cohorts. These patients will be exposed to FPV/RTV or LPV/RTV.

Drug: Intervention A Standard doseDrug: Intervention B Reduced DoseDrug: Intervention CDrug: Intervention DDrug: Intervention E

Interventions

Intervention A Standard doseDRUG

HIV subjects with HBV or HCV co-infection but normal hepatic function, defined by receipt of FPV 700mg BID/RTV 100mg BID and a baseline AST-platelet ratio index (APRI) score of \<2.0.