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: April 10, 2014
Last verified: April 2014
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  
COMPLETED     13     51  
NOT COMPLETED     7     38  
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                 4  
Poor Medical Compliance/Adherence Issues                 0                 3  
Participant Management Criteria Met                 0                 1  
Reason Not Provided                 0                 1  
Protocol Violation                 0                 3  
Principal Investigator Decision                 0                 10  
Start of Disallowed Medication                 0                 1  
Necessity to Use Prohibited Drug                 1                 0  
Participant Incarcerated                 0                 1  



  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 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
  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 ]

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

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

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

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

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

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

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

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 ]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 ]
  Hide Outcome Measure 26

Measure Type Secondary
Measure Title Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48
Measure Description Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced.Virologic success was defined as plasma HIV-1 RNA <400 copies/mL. Virologic failure: (1) HIV-1 RNA >=400 copies/mL, (2) change of background antiretroviral treatment (ART), (3) discontinued study due to lack of efficacy, (4) discontinued study with last HIV-1 >=400 copies/mL. No virologic data at Week 48 window: (a) discontinued study due to an adverse event or death, (b) discontinued study due to other reasons, (c) missing data during window but still on study.
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.
Intent-to-Treat Exposed (ITT-E) Population: par. with documented evidence of receiving >=1 treatment dose. Only par. contributing data were analyzed. The number of par. analyzed is the sum of the PI-naïve (received <1week's treatment with a PI) and -experienced (received >1week prior PI therapy with no more than 3 PIs before trial enrollment) par.

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]
  20     89  
Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48  
[units: participants]
   
PI-naïve, virological (V) success; n=20, 49     12     36  
PI-exp, V success; n=0, 40     NA [1]   19  
PI-naïve, V failure (1); n=20, 49     4     3  
PI-exp, V failure (1); n=0, 40     NA [1]   8  
PI-naïve, V failure (2); n=20, 49     2     4  
PI-exp, V failure (2); n=0, 40     NA [1]   7  
PI-naïve, V failure (3); n=20, 49     1     0  
PI-exp, V failure (3); n=0, 40     NA [1]   0  
PI-naïve;, V failure (4); n=20, 49     1     3  
PI-exp, V failure (4); n=0, 40     NA [1]   3  
PI-naïve, No V data at Week 48 (a); n=20, 49     0     1  
PI-exp, No V data at Week 48 (a); n=0, 40     NA [1]   1  
PI-naïve, No V data Week 48 (b); n=20, 49     0     1  
PI-exp, No V data at Week 48 (b); n=0, 40     NA [1]   0  
PI-naïve, No V data at Week 48 (c); n=20, 49     0     1  
PI-exp, No V data at Week 48 (c); n=0, 40     NA [1]   2  
[1] No participants were analyzed for this population at this time point.

No statistical analysis provided for Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48



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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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

36.  Secondary:   Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease   [ Time Frame: After Week 48 through Week 240 ]

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

38.  Secondary:   Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS)   [ Time Frame: Week 60 through Week 240 ]

39.  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 ]

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


  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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