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
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 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
  Show All Outcome Measures

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 ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title 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
Measure Description A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV
Time Frame Incidence was assessed over time during Year 1  
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 milligrams (mg) twice a day (BID)/Ritonavir 100 mg BID
FPV 700 mg BID/RTV 100 mg QD Fosamprenavir 700 mg BID/Ritonavir 100 mg once a day (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  
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  
[units: events]
  9     1     4     19  


Statistical Analysis 1 for 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
Groups [1] FPV 700 mg BID/RTV 100 mg BID vs. LPV, Standard Dose
Method [2] Regression, Cox
P Value [3] 0.72
Hazard Ratio (HR) [4] 1.16
95% Confidence Interval ( 0.51 to 2.66 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Only variables showing an imbalance between treatment groups were included: gender, mode of HIV transmission, ART naive, use of non-ARV drug, baseline bilirubin.
[4] Other relevant estimation information:
  Confidence Interval and Hazard Ratio for " FPV 700 mg BID/RTV 100 mg BID". "LPV" is the reference group.

Statistical Analysis 2 for 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
Groups [1] FPV 700 mg BID/RTV 100 mg QD vs. LPV, Standard Dose
Method [2] Regression, Cox
P Value [3] 0.21
Hazard Ratio (HR) [4] 0.27
95% Confidence Interval ( 0.03 to 2.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Only variables showing an imbalance between treatment groups were included: gender, mode of HIV transmission, ART naive, use of non-ARV drug, baseline bilirubin.
[4] Other relevant estimation information:
  Confidence Interval and Hazard Ratio for " FPV 700 mg BID/RTV 100 mg QD". "LPV" is the reference group.

Statistical Analysis 3 for 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
Groups [1] FPV, Other vs. LPV, Standard Dose
Method [2] Regression, Cox
P Value [3] 0.15
Hazard Ratio (HR) [4] 2.26
95% Confidence Interval ( 0.74 to 6.97 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Only variables showing an imbalance between treatment groups were included: gender, mode of HIV transmission, ART naive, use of non-ARV drug, baseline bilirubin.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Confidence Interval and Hazard Ratio for " FPV, other". "LPV" is the reference group.



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 ]

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


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01054586     History of Changes
Other Study ID Numbers: 111949, WEUKSTV2430, EPI40537
Study First Received: January 21, 2010
Results First Received: January 14, 2011
Last Updated: May 2, 2013
Health Authority: United Kingdon: No Health Authority