Fosamprenavir in Pts With Hepatic Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01054586
First received: January 21, 2010
Last updated: May 2, 2013
Last verified: April 2013
Results First Received: January 14, 2011  
Study Type: Observational
Study Design: Observational Model: Cohort;   Time Perspective: Prospective
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: Intervention A Standard dose
Drug: Intervention B Reduced Dose
Drug: Intervention C
Drug: Intervention D
Drug: Intervention E

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
As this was an observational, retrospective study, no participants were recruited for participation in this study. For more information about this study, see the protocol in ClinicalTrials.gov and/or search for this study (111949) on http://www.gsk-clinicalstudyregister.com/.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
FPV 700 mg BID/RTV 100 mg BID Fosamprenavir 700 milligrams (mg) twice a day (BID)/Ritonavir 100 mg BID
FPV 700 mg BID/RTV 100 mg QD FPV 700 mg BID/RTV 100 mg once a day (QD)
FPV, Other All other dosages of FPV (excluding FPV 700 mg BID/RTV 100 mg BID and FPV 700 mg BID/RTV 100 mg QD)
LPV, Standard Dose Lopinavir (LPV), Standard Dose

Participant Flow:   Overall Study
    FPV 700 mg BID/RTV 100 mg BID     FPV 700 mg BID/RTV 100 mg QD     FPV, Other     LPV, Standard Dose  
STARTED     43     15     8     101  
COMPLETED     43     15     8     101  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FPV 700 mg BID/RTV 100 mg BID Fosamprenavir 700 milligrams (mg) twice a day (BID)/Ritonavir 100 mg BID
FPV 700 mg BID/RTV 100 mg QD FPV 700 mg BID/RTV 100 mg once a day (QD)
FPV, Other All other dosages of Fosamprenavir
LPV, Standard Dose Lopinavir (LPV), Standard Dose
Total Total of all reporting groups

Baseline Measures
    FPV 700 mg BID/RTV 100 mg BID     FPV 700 mg BID/RTV 100 mg QD     FPV, Other     LPV, Standard Dose     Total  
Number of Participants  
[units: participants]
  43     15     8     101     167  
Age  
[units: years]
Median ( Full Range )
  45  
  ( 36 to 62 )  
  45  
  ( 29 to 51 )  
  44  
  ( 36 to 53 )  
  44  
  ( 25 to 74 )  
  44  
  ( 25 to 74 )  
Gender  
[units: participants]
         
Female     11     3     0     38     52  
Male     32     12     8     63     115  
Cohort Distribution [1]
[units: participants]
         
Cohort - MASTER     36     13     4     72     125  
Cohort - HEPAVIH     3     2     2     6     13  
Cohort - ICONA     4     0     2     23     29  
Number of participants positive for Hepatitis B and/or C at baseline [2]
[units: participants]
         
HCV-Ab positive test     37     14     7     82     140  
HBs-Ag positive test     9     2     2     21     34  
Number of participants who were ART naïve at baseline [3]
[units: participants]
  12     5     2     50     69  
Number of participants with acquired immunodeficiency syndrome (AIDS) at baseline [4]
[units: participants]
  9     0     3     24     36  
Number of participants with the indicated alanine aminotransferase (ALT) levels at baseline [5]
[units: participants]
         
Baseline ALT <= 200 IU/L     40     11     6     83     140  
Baseline ALT > 200 IU/L     1     2     1     3     7  
Baseline ALT Unknown     2     2     1     15     20  
[1] Source population from three human immunodeficiency virus (HIV)-infected patient cohorts: ICONA (Italian Cohort of Antiretroviral Naïve Patients), treatment naïve participants at initial presentation in Italy; HEPAVIH, HIV-hepatitis coinfected in France; MASTER (Management Standardizzato di Terapia Antiretrovirale), HIV-infected participants who are either treatment experienced or naïve patients in Italy
[2] Participant characteristics at baseline according to treatment group. Participants were tested for Hepatitis C antibody (HCV-Ab) and Hepatitis B surface antigen (HBs-Ag).
[3] Participant characteristics at baseline according to treatment group. The number of participants who had not received antiretroviral therapy (ART) was recorded.
[4] Participant characteristics at baseline according to treatment group. The number of participants with AIDS was recorded.
[5] Participant characteristics at baseline according to treatment group. The number of participants with the indicated ALT levels was recorded. IU/L = International Units per Liter.



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   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 ]

7.  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   [ Time Frame: Incidence was assessed over time during Year 1 ]

8.  Secondary:   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 ]

9.  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)   [ Time Frame: Incidence was assessed over time during Year 1 ]

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 FIB-score and Other Variables   [ Time Frame: Incidence was assessed over time during Year 1 ]

11.  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   [ Time Frame: Incidence was assessed over time during Year 1 ]

12.  Secondary:   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 ]

13.  Secondary:   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 ]

14.  Secondary:   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 ]

15.  Secondary:   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 ]

16.  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   [ Time Frame: The incidence of these events was assessed over time during Year 1 ]

17.  Secondary:   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 ]

18.  Other Pre-specified:   Median Length of Participant Follow-up and Length of Time on Antiretroviral Therapy (ART) at Baseline   [ Time Frame: Baseline ]

19.  Other Pre-specified:   Cluster of Differentiation (CD4) Count at Baseline   [ Time Frame: Baseline ]

20.  Other Pre-specified:   Median Aspartate Aminotransferase (AST)-Platelet Ratio Index (APRI) Score at Baseline   [ Time Frame: Baseline ]

21.  Other Pre-specified:   Median FIB (a Model of End-stage Liver Disease) Score at Baseline   [ Time Frame: Baseline ]
  Hide Outcome Measure 21

Measure Type Other Pre-specified
Measure Title Median FIB (a Model of End-stage Liver Disease) Score at Baseline
Measure Description 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).
Time Frame Baseline  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
HIV/hepatitis virus co-infected participants enrolled in a number of cohort studies in Europe

Reporting Groups
  Description
FPV 700 mg BID/RTV 100 mg BID Fosamprenavir 700 mg BID/Ritonavir 100 mg BID
FPV 700 mg BID/RTV 100 mg QD Fosamprenavir 700 mg BID/Ritonavir 100 mg QD
FPV, Other All other dosages of Fosamprenavir
LPV, Standard Dose Lopinavir, Standard Dose

Measured Values
    FPV 700 mg BID/RTV 100 mg BID     FPV 700 mg BID/RTV 100 mg QD     FPV, Other     LPV, Standard Dose  
Number of Participants Analyzed  
[units: participants]
  43     15     8     101  
Median FIB (a Model of End-stage Liver Disease) Score at Baseline  
[units: FIB┬áScore]
Median ( Full Range )
  0.49  
  ( 0.17 to 3.00 )  
  0.64  
  ( 0.18 to 5.87 )  
  1.96  
  ( 0.25 to 13.47 )  
  0.74  
  ( 0.19 to 4.38 )  

No statistical analysis provided for Median FIB (a Model of End-stage Liver Disease) Score at Baseline



22.  Other Pre-specified:   Median Model of End-stage Liver Disease (MELD) Score at Baseline   [ Time Frame: Baseline ]

23.  Other Pre-specified:   Median ALT and AST Scores at Baseline   [ Time Frame: Baseline ]

24.  Other Pre-specified:   Median Blood Platelet Count at Baseline   [ Time Frame: Baseline ]

25.  Other Pre-specified:   Median Bilirubin Level at Baseline   [ Time Frame: Baseline ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information