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Completed

NCT Number: NCT01054586

Fosamprenavir in Pts With 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.

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Key information

Conditions

Infection, Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intervention A Standard dose

Drug

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.

Intervention B Reduced Dose

Drug

HIV subjects with mild hepatic impairment, defined by receipt of the recommended reduced FPV/RTV dose (700mg BID/100mg QD).

Intervention C

Drug

HIV subjects with moderate hepatic impairment, defined by receipt of FPV 450mg BID/RTV 100mg QD.

Intervention D

Drug

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.

Intervention E

Drug

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.

Primary outcomes

  1. 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

    An elevation in ALT is defined as a single value >200 IU/I.

  2. 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.

  3. 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.

  4. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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).

  10. 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

  11. 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

  12. 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)

  13. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. Median ALT and AST Scores at Baseline

    Time frame: Baseline

    Participants characteristics at baseline according to treatment group.

  7. Median Blood Platelet Count at Baseline

    Time frame: Baseline

    Participant characteristics at baseline according to treatment group.

  8. Median Bilirubin Level at Baseline

    Time frame: Baseline

    Participant characteristics at baseline according to treatment group.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

HI FPV Study: Using Observational Cohorts to Monitor Safety of Fosamprenavir in Patients With Mild/Moderate Hepatic Impairment

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Jan 22, 2010
Registry last updated
May 7, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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