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

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

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.  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 ]

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.) With Treatment-emergent Reductions in Drug Susceptibility (DS)   [ Time Frame: Baseline through 48 Weeks ]

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 ]

38.  Secondary:

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