- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01054586
Fosamprenavir in Pts With Hepatic Impairment
HI FPV Study: Using Observational Cohorts to Monitor Safety of Fosamprenavir in Patients With Mild/Moderate Hepatic Impairment
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
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.
HIV subjects with mild hepatic impairment, defined by receipt of the recommended reduced FPV/RTV dose (700mg BID/100mg QD).
HIV subjects with moderate hepatic impairment, defined by receipt of FPV 450mg BID/RTV 100mg QD.
HIV subjects receiving the standard dose of FPV/RTV despite evidence of abnormal hepatic function according to APRI score: HIV subjects with HBV or HCV co-infection, receipt of FPV 700mg BID/RTV 100mg BID and a baseline APRI score of ≥2.0.
HIV subjects coinfected with HBV or HCV who have initiated standard doses of LPV 400mg/RTV 100mg and enrolled in the same cohorts as the FPV/RTV exposed subjects.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables
Time Frame: The incidence of these events was assessed over time during Year 1, censoring participants' follow-up at date of last ALT
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An elevation in ALT is defined as a single value >200 IU/I.
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The incidence of these events was assessed over time during Year 1, censoring participants' follow-up at date of last ALT
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Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for APRI-score, and Other Variables
Time Frame: Incidence of these events was assessed over time during Year 1, censoring patients' follow-up at date of last ALT
|
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
Time Frame: Incidence was assessed over time during Year 1
|
An elevation in ALT is defined as a single value >200 IU/I.
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Incidence was assessed over time during Year 1
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Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts
Time Frame: Incidence was assessed over time during Year 1
|
An elevation in ALT is defined as a single value >200 IU/I.
|
Incidence was assessed over time during Year 1
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV.
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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
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV.
|
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
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV
|
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
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attritubed 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)
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime
|
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 FIB-score and Other Variables
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime.
|
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 Current Values of CD4 and Platelet Counts
Time Frame: Incidence was assessed over time during Year 1
|
A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime.
|
Incidence was assessed over time during Year 1
|
Number of Events of Discontinuation of One or More Drugs in the FPV/RTV- or LPV/RTV Regimen Due to Adverse Events Only
Time Frame: Incidence was assessed over time during Year 1
|
Defined as the occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attributed to adverse events only
|
Incidence was assessed over time during Year 1
|
Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to the Indicated Adverse Events
Time Frame: Incidence was assessed over time during Year 1
|
Defined as the first occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attributed to adverse events only.
Adverse events can only be attributed to the body system stated (no further specificity is available).
|
Incidence was assessed over time during Year 1
|
Number of Participants Who Discontinued the Indicated Antiretrovirals for the First Time After Starting FPV/r or LPV/r
Time Frame: Assessed over time during Year 1
|
Antiretrovirals discontinued for the first time after starting FPV/r or LPV/r
|
Assessed over time during Year 1
|
Number of Participants With the Indicated Major Reasons for Discontinuing One or More Drugs in the FPV/r or LPV/r Regimen
Time Frame: Assessed over time during Year 1
|
Major reasons for discontinuing one or more drugs in the FPV/r or LPV/r regimen
|
Assessed over time during Year 1
|
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
Time Frame: The incidence of these events was assessed over time during Year 1
|
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.
Adverse events can only be attributed to the body system stated (no further specificity is available)
|
The incidence of these events was assessed over time during Year 1
|
Incidence Rates Per 100 Person-years of Follow-up (PYFU) of Study Main Outcome Measures
Time Frame: Incidence of these events was assessed over time during Year 1
|
Incidence rates per 100 person-years of follow-up of study primary outcome.
The numbers analyzed in the category titles represent the number of patients with each event.
Incidence rate is the number of new cases per population in a given time period, where the denominator is the sum of the person-time of the at-risk population.
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Incidence of these events was assessed over time during Year 1
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Length of Participant Follow-up and Length of Time on Antiretroviral Therapy (ART) at Baseline
Time Frame: Baseline
|
Participant characteristics at baseline are presented according to treatment group.
ART is used for the treatment of HIV.
|
Baseline
|
Cluster of Differentiation (CD4) Count at Baseline
Time Frame: Baseline
|
Participant characteristics at baseline according to treatment group.
CD4 count is a measurement of how many functional CD4 T-cells are circulating in the blood.
The lower the absolute CD4 count, the weaker the immune system.
|
Baseline
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Median Aspartate Aminotransferase (AST)-Platelet Ratio Index (APRI) Score at Baseline
Time Frame: Baseline
|
The APRI score (AST to platelet ratio index) is an index comprised of biochemical values and is used to determine the degree of hepatic fibrosis.
It is calculated as follows: APRI score = ([AST level/Upper Limit Normal]/Platelet counts) x 100.
AST = Aspartate aminotransferase.
In general, APRI scores range from 0 to >2.0, where scores <0.5 indicate no significant fibrosis, scores >1.5 indicate significant fibrosis, and scores >2.0 have been shown to be best correlated with the presence of cirrhosis.
|
Baseline
|
Median FIB (a Model of End-stage Liver Disease) Score at Baseline
Time Frame: Baseline
|
The FIB-4 score is an index that combines biochemical values (platelets, ALT, AST) and age to determine the degree of hepatic fibrosis.
FIB-4 = (Age x AST)/(Platelet counts x ALT1/2).
The FIB-4 score ranges between values of 0 to 13.
A score of <1.45 indicates no/moderate fibrosis (F0-F1-F2-F3 in the ISHAK classification of fibrosis), whereas a score >3.25 is indicative of extensive fibrosis or cirrhosis (F4-F5-F6).
The ISHAK classification of fibrosis is a commonly used scoring system that stages fibrosis from 0-6 (1-2, portal fibrotic expansion; 3-4, bridging fibrosis; 5-6, cirrhosis).
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Baseline
|
Median Model of End-stage Liver Disease (MELD) Score at Baseline
Time Frame: Baseline
|
MELD is a scoring system for assessing the severity of chronic liver disease and is used to predict participant survival.
It is calculated using biochemical values as follows: MELD = (0.957 x Log[Creatinine]) + (0.378 x Log[Bilirubin]) + (1.120 x Log[INR]) + 0.6431.
INR = International Normalized Ratio for prothrombin time.
MELD scores range between 0 and 40, with 40 being the most severe, i.e., 100% mortality.
In interpreting the MELD score in hospitalized participants, the 3-month mortality is: score >=40, 100% mortality; 30-39, 83% mortality; 20-29, 76% mortality; 10-19, 27% mortality.
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Baseline
|
Median ALT and AST Scores at Baseline
Time Frame: Baseline
|
Participants characteristics at baseline according to treatment group.
|
Baseline
|
Median Blood Platelet Count at Baseline
Time Frame: Baseline
|
Participant characteristics at baseline according to treatment group.
|
Baseline
|
Median Bilirubin Level at Baseline
Time Frame: Baseline
|
Participant characteristics at baseline according to treatment group.
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Baseline
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
Other Study ID Numbers
- 111949
- WEUKSTV2430 (Other Identifier: GSK)
- EPI40537 (Other Identifier: GSK)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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