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48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00089583
First received: August 6, 2004
Last updated: December 6, 2012
Last verified: December 2012
History of Changes
Results First Received: February 24, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus I
Interventions: Drug: LEXIVA (GW433908)
Drug: Ritonavir

  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
A total of 110 participants (par.) were enrolled in the study; however, 1 par. withdrew from the study prior to the first dose of study drug and was not included in the Intent-to-Treat Exposed or Safety Populations. Therefore, 109 par. received >=1 dose of study drug and are thus categorized as starting the study in the Participant Flow module.

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 Treatment Group Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs).
FPV/RTV Treatment Group HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent.

Participant Flow:   Overall Study
    FPV Treatment Group     FPV/RTV Treatment Group  
STARTED     20     89  
Ongoing     0     6  
COMPLETED     13     43  
NOT COMPLETED     7     46  
Adverse Event                 0                 3  
Insufficient Viral Load Response                 5                 5  
Withdrawal by Subject                 0                 4  
Participant (Par) Didn't Take Medication                 1                 0  
Participant Refused Study Medication                 0                 2  
Non-Compliance                 0                 2  
Poor Medical Compliance/Adherence Issues                 0                 4  
Participant Management Criteria Met                 0                 1  
Reason Not Provided                 0                 1  
Protocol Violation                 0                 2  
Par 18 Years, Commercial FPV Available                 0                 1  
Principle Investigator Decision                 0                 10  
Participant Refused Liquid                 0                 1  
Start of Disallowed Medication                 0                 1  
Necessity to Use Prohibited Drug                 1                 0  
Participant Incarcerated                 0                 1  
Par >6 Years Old and Dosage Approved                 0                 1  
Participant Moved to Adult Clinic                 0                 1  
Ongoing                 0                 6  



  Baseline Characteristics
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Reporting Groups
  Description
FPV Treatment Group Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs).
FPV/RTV Treatment Group HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent.
Total Total of all reporting groups

Baseline Measures
    FPV Treatment Group     FPV/RTV Treatment Group     Total  
Number of Participants  
[units: participants]
 		  20     89     109  
Age  
[units: Years]
Mean ± Standard Deviation 		     
Years     2.9  ± 1.07     10.0  ± 4.49     8.7  ± 4.93  
Gender  
[units: Participants]
 		     
Female     15     43     58  
Male     5     46     51  
Race/Ethnicity, Customized  
[units: participants]
 		     
Arabic/North African     0     1     1  
Black     0     43     43  
South Asian     0     1     1  
White/Caucasian     19     41     60  
Race Not Specified     1     3     4  
Par with the Indicated 1993 Center for Disease Control and Prevention (CDC) Baseline Classification [1]
[units: participants]
 		     
<13 years (yrs); mildly symptomatic (S)     18     26     44  
<13 yrs; moderately S     1     15     16  
<13 yrs; severely S     0     10     10  
<13 yrs; non-S     1     5     6  
>=13 yrs; asymptomatic/lymphadenopathy/acute HIV     0     12     12  
>=13 yrs; asymptomatic, not AIDS     0     14     14  
>=13 yrs; AIDS     0     5     5  
>=13 yrs; not reported     0     2     2  
[1] The adult/adolescent (>=13 years) HIV infection CDC classification system was based on 3 categories (Cat). Cat A, asymptomatic acute/primary HIV infection or persistent generalized lymphadenopathy. Cat B, symptomatic conditions not included in Cat A or C but attributed to a cell-mediated immunity defect or for which the clinical course or management was complicated by HIV infection. Cat C, acquired immune deficiency syndrome (AIDS)-defining conditions. Infected children (<13 years) are classified into mutually exclusive categories per 3 parameters: infection, clinical, and immunologic status.



  Outcome Measures
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1.  Primary:   Plasma Amprenavir (APV) AUC (0-tau[τ])   [ Time Frame: Week 48 ]
  Show Outcome Measure 1

2.  Primary:   Plasma APV Cmax   [ Time Frame: Week 48 ]
  Show Outcome Measure 2

3.  Primary:   Plasma APV Cτ   [ Time Frame: Week 48 ]
  Show Outcome Measure 3

4.  Primary:   Plasma APV CL/F Following Dosing Expressed in mg/kg   [ Time Frame: Week 48 ]
  Hide Outcome Measure 4

Measure Type Primary
Measure Title Plasma APV CL/F Following Dosing Expressed in mg/kg
Measure Description Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: APV Dose in mg/kg units divided by AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.
Time Frame Week 48  
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.
PK Population. Only those participants contributing data were analyzed.

Reporting Groups
  Description
FPV Treatment Group Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs).
FPV/RTV Treatment Group HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-&lt;6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent.

Measured Values
    FPV Treatment Group     FPV/RTV Treatment Group  
Number of Participants Analyzed  
[units: participants]
 		  9     14  
Plasma APV CL/F Following Dosing Expressed in mg/kg  
[units: Milliliters/minute/kilogram (mL/min/kg)]
Geometric Mean ( 95% Confidence Interval ) 		   
2 to <6yrs, 30 mg/kg BID; n=9, 0     19.3  
  ( 13.2 to 28.2 )   		  NA  
  ( NA to NA ) [1]
2 to <6yrs, 40 mg/kg BID; n=7, 0     23.4  
  ( 14.9 to 36.8 )   		  NA  
  ( NA to NA ) [1]
2 to <6yrs, 23/3 mg/kg BID; n=0, 14     NA  
  ( NA to NA ) [1] 		  6.06  
  ( 4.12 to 8.91 )  
6 to <12 yrs, 15/3 mg/kg BID; n=0, 9     NA  
  ( NA to NA ) [1] 		  6.48  
  ( 4.68 to 8.98 )  
6 to <12 yrs, 18/3 mg/kg BID; n=0, 12     NA  
  ( NA to NA ) [1] 		  5.27  
  ( 4.16 to 6.68 )  
6 to <12 yrs, 700/100 mg BID; n=0, 3     NA  
  ( NA to NA ) [1] 		  5.94  
  ( 2.59 to 13.9 )  
12 to 18 yrs, 15/3 mg/kg BID; n=0, 4     NA  
  ( NA to NA ) [1] 		  10.1  
  ( 8.35 to 12.3 )  
12 to 18 yrs, 18/3 mg BID; n=0, 3     NA  
  ( NA to NA ) [1] 		  6.00  
  ( 2.37 to 15.2 )  
12 to 18 yrs, 700/100 mg BID; n=0, 13     NA  
  ( NA to NA ) [1] 		  5.33  
  ( 4.26 to 6.68 )  
[1] No participants were analyzed at this dose in this age group.

No statistical analysis provided for Plasma APV CL/F Following Dosing Expressed in mg/kg



5.  Primary:   Plasma APV CL/F Following Dosing Expressed in mg   [ Time Frame: Week 48 ]
  Show Outcome Measure 5

6.  Primary:   Plasma APV Tmax   [ Time Frame: Week 48 ]
  Show Outcome Measure 6

7.  Primary:   Plasma APV t1/2   [ Time Frame: Week 48 ]
  Show Outcome Measure 7

8.  Primary:   Number of Participants Who Permanently Discontinued the Treatment Due to Any Adverse Event (AE)   [ Time Frame: Week 48 ]
  Show Outcome Measure 8

9.  Primary:   Change From Baseline in Triglycerides, Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Serum Glucose at Week 48   [ Time Frame: Baseline (Day 1) and Week 48 ]
  Show Outcome Measure 9

10.  Primary:   Change From Baseline in Serum Lipase at Week 48   [ Time Frame: Baseline (Day 1) and Week 48 ]
  Show Outcome Measure 10

11.  Primary:   Change From Baseline in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at Week 48   [ Time Frame: Baseline (Day 1) and Week 48 ]
  Show Outcome Measure 11

12.  Primary:   Number of Participants With Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Laboratory Abnormalities   [ Time Frame: Baseline (Day 1) until Week 48 ]
  Show Outcome Measure 12

13.  Secondary:   Plasma Ritonavir (RTV) AUC (0-τ)   [ Time Frame: Week 48 ]
  Show Outcome Measure 13

14.  Secondary:   Plasma RTV Cmax   [ Time Frame: Week 48 ]
  Show Outcome Measure 14

15.  Secondary:   Plasma RTV Cτ   [ Time Frame: Week 48 ]
  Show Outcome Measure 15

16.  Secondary:   Plasma RTV CL/F Following Dosing Expressed in mg/kg   [ Time Frame: Week 48 ]
  Show Outcome Measure 16

17.  Secondary:   Plasma RTV CL/F Following Dosing Expressed in mg   [ Time Frame: Week 48 ]
  Show Outcome Measure 17

18.  Secondary:   Plasma RTV Tmax   [ Time Frame: Week 48 ]
  Show Outcome Measure 18

19.  Secondary:   Plasma RTV t1/2   [ Time Frame: Week 48 ]
  Show Outcome Measure 19

20.  Secondary:   Plasma FPV AUC (0-τ)   [ Time Frame: Week 48 ]
  Show Outcome Measure 20

21.  Secondary:   Plasma FPV Cmax and Cτ   [ Time Frame: Week 48 ]
  Show Outcome Measure 21

22.  Secondary:   Plasma FPV CL/F Following Dosing Expressed in mg/kg   [ Time Frame: Week 48 ]
  Show Outcome Measure 22

23.  Secondary:   Plasma FPV CL/F Following Dosing Expressed in mg   [ Time Frame: Week 48 ]
  Show Outcome Measure 23

24.  Secondary:   Plasma FPV Tmax   [ Time Frame: Week 48 ]
  Show Outcome Measure 24

25.  Secondary:   Plasma FPV t1/2   [ Time Frame: Week 48 ]
  Show Outcome Measure 25

26.  Secondary:   Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 26

27.  Secondary:   Number of Participants (Par.) With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 2,12, 24, and 48 (MSD=F)   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 27

28.  Secondary:   Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis)   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 28

29.  Secondary:   Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis)   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 29

30.  Secondary:   Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 2, 12, 24, and 48 (Observed Analysis)   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 30

31.  Secondary:   Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 2, 12, 24, and 48   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 31

32.  Secondary:   Change From Baseline in CD4+ Cell Count at Weeks 2, 12, 24, and 48   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 32

33.  Secondary:   Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Baseline and Weeks 2, 12, 24, and 48   [ Time Frame: Baseline and Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 33

34.  Secondary:   Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Weeks 2, 12, 24, and 48   [ Time Frame: Baseline and Week 2, 12, 24, 48 ]
  Show Outcome Measure 34

35.  Secondary:   Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease   [ Time Frame: Week 48 ]
  Show Outcome Measure 35

36.  Secondary:   Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS)   [ Time Frame: Baseline through 48 Weeks ]
  Show Outcome Measure 36

37.  Secondary:   Number of Participants Reporting Perfect Adherence Over the 3 Days Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by Study Coordinator Using the Pediatric AIDS Clinical Trials Group (PACTG) Adherence Questionnaire   [ Time Frame: Weeks 2, 12, 24, and 48 ]
  Show Outcome Measure 37

38.  Secondary:   Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events   [ Time Frame: Week 48 ]
  Show Outcome Measure 38


  Serious Adverse Events
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  Other Adverse Events
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  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: ViiV Healthcare
phone: 866-435-7343


No publications provided


Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00089583     History of Changes
Other Study ID Numbers: APV29005
Study First Received: August 6, 2004
Results First Received: February 24, 2012
Last Updated: December 6, 2012
Health Authority: Spain: Spanish Agency of Medicines
United States: Food and Drug Administration