Infection, Human Immunodeficiency Virus Clinical Trial
Official title:
HI FPV Study: Using Observational Cohorts to Monitor Safety of Fosamprenavir in Patients With Mild/Moderate Hepatic Impairment
Verified date | April 2013 |
Source | GlaxoSmithKline |
Contact | n/a |
Is FDA regulated | No |
Health authority | United Kingdon: No Health Authority |
Study type | Observational |
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.
Status | Completed |
Enrollment | 167 |
Est. completion date | March 2012 |
Est. primary completion date | March 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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. |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
GlaxoSmithKline |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Median Length of Participant Follow-up and Length of Time on Antiretroviral Therapy (ART) at Baseline | Participant characteristics at baseline are presented according to treatment group. ART is used for the treatment of HIV. | Baseline | No |
Other | Cluster of Differentiation (CD4) Count at 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 | No |
Other | Median Aspartate Aminotransferase (AST)-Platelet Ratio Index (APRI) Score at 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 | No |
Other | Median FIB (a Model of End-stage Liver Disease) Score at 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). | Baseline | No |
Other | Median Model of End-stage Liver Disease (MELD) Score at 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. | Baseline | No |
Other | Median ALT and AST Scores at Baseline | Participants characteristics at baseline according to treatment group. | Baseline | No |
Other | Median Blood Platelet Count at Baseline | Participant characteristics at baseline according to treatment group. | Baseline | No |
Other | Median Bilirubin Level at Baseline | Participant characteristics at baseline according to treatment group. | Baseline | No |
Primary | 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 | Yes |
Primary | 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 | No |
Primary | 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 | No |
Primary | 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 | No |
Secondary | Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV. | Incidence was assessed over time during Year 1 | No |
Secondary | Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for FIB-score, and Other Variables | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV. | Incidence was assessed over time during Year 1 | No |
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 | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV | Incidence was assessed over time during Year 1 | No |
Secondary | Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to Adverse Events Only | 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 | No |
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) | 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 | No |
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 | 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 | No |
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 | 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 | No |
Secondary | Number of Events of Discontinuation of One or More Drugs in the FPV/RTV- or LPV/RTV Regimen Due to Adverse Events Only | 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 | No |
Secondary | Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to the Indicated Adverse Events | 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 | No |
Secondary | Number of Participants Who Discontinued the Indicated Antiretrovirals for the First Time After Starting FPV/r or LPV/r | Antiretrovirals discontinued for the first time after starting FPV/r or LPV/r | Assessed over time during Year 1 | No |
Secondary | Number of Participants With the Indicated Major Reasons for Discontinuing One or More Drugs in the FPV/r or LPV/r Regimen | Major reasons for discontinuing one or more drugs in the FPV/r or LPV/r regimen | Assessed over time during Year 1 | No |
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 | 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 | No |
Secondary | Incidence Rates Per 100 Person-years of Follow-up (PYFU) of Study Main Outcome Measures | 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. | Incidence of these events was assessed over time during Year 1 | No |
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