N/A
N=167
Fosamprenavir in Pts With Hepatic Impairment
Infection, Human Immunodeficiency Virus
Bottom Line
View on ClinicalTrials.gov: NCT01054586 ↗Enrolled (actual)
167
Serious AEs
—
Results posted
Jun 2011
Primary outcome: Primary: Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables — 9; 4 events — p=0.02
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Intervention A Standard dose (Drug); Intervention B Reduced Dose (Drug); Intervention C (Drug); Intervention D (Drug); Intervention E (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Mar 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables |
9; 4 | 0.02 sig |
| PRIMARY Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for APRI-score, and Other Variables |
6; 1; 6 | 0.05 |
| PRIMARY Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for FIB-score, and Other Variables |
6; 1; 6 | 0.17 |
| PRIMARY Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts |
6; 1; 6 | 0.06 |
| SECONDARY Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables |
9; 1; 4; 19 | 0.57 |
| SECONDARY Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for FIB-score, and Other Variables |
9; 1; 4; 19 | 0.48 |
| SECONDARY 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 |
9; 1; 4; 19 | 0.72 |
| SECONDARY Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to Adverse Events Only |
5; 7 | 0.10 |
| SECONDARY 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) |
16; 8; 5; 24 | 0.02 sig |
| SECONDARY 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 |
16; 8; 5; 24 | 0.01 sig |
| SECONDARY 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 |
16; 8; 5; 24 | 0.03 sig |
| SECONDARY Number of Events of Discontinuation of One or More Drugs in the FPV/RTV- or LPV/RTV Regimen Due to Adverse Events Only |
3; 5 | 0.03 sig |
| SECONDARY Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to the Indicated Adverse Events |
1; 5; 1; 2; 1; 3 | — |
| SECONDARY Number of Participants Who Discontinued the Indicated Antiretrovirals for the First Time After Starting FPV/r or LPV/r |
11; 7; 2; 0; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Major Reasons for Discontinuing One or More Drugs in the FPV/r or LPV/r Regimen |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY 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 |
2; 6; 1; 2; 1; 3 | — |
| SECONDARY Incidence Rates Per 100 Person-years of Follow-up (PYFU) of Study Main Outcome Measures |
18; 55; 102; 0; 1 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT01054586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.