Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
59 unique participants (par.) received >=1 investigational product (IP) dose; however, 1 par. was not given a randomization number and therefore was not enrolled into the study. Thus, the number of par. enrolled in the protocol record=58. 5/59 par. receiving only single doses of IP are not included in the Intent-to-Treat Exposed Population (N=54).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Per protocol, the initial intention was to enroll par. to receive fosamprenavir; however, ultimately, no par. were enrolled into cohorts to receive repeat dosing of fosamprenavir without ritonavir boosting. The 59 par. who received >=1 IP dose were included in the Safety Population.

Reporting Groups

Description

FPV/RTV BID

Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.

Participant Flow:   Overall Study

	FPV/RTV BID
STARTED	54
Ongoing	25
COMPLETED	0
NOT COMPLETED	54
Adverse Event	3
Lost to Follow-up	4
Protocol Violation	1
Withdrawal by Subject	3
Insufficient Viral Load Response	3
Pulmonary Tuberculosis	1
Unavailability of RTV	8
Relocation	1
Investigator's Recommendation (Rec.)	4
Study Team Rec./Resistance	1
Ongoing	25

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 mL/Min/kg   [ Time Frame: Week 48 ]

5.  Primary:

Plasma APV CL/F Following Dosing Expressed in mL/Min   [ Time Frame: Week 48 ]

6.  Primary:

Plasma Unbound APV Cτ   [ Time Frame: Week 48 ]

7.  Primary:

Plasma Unbound APV Percent Protein Binding (%Cτ)   [ Time Frame: Week 48 ]

8.  Primary:

Median Change From Baseline in Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) at Weeks 4, 12, 24, 36, and 48   [ Time Frame: Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48 ]

9.  Primary:

Median Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Triglyceride (TG), Potassium, and Sodium at Weeks 4, 12, 24, 36, and 48   [ Time Frame: Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48 ]

10.  Primary:

Median Change From Baseline in Serum Lipase at Weeks 4, 12, 24, and 48   [ Time Frame: Baseline (Day 1) and Weeks 4, 12, 24, and 48 ]

11.  Primary:

Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities   [ Time Frame: Baseline (Day 1) until Week 48 ]

12.  Primary:

Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Adverse Events (AE)   [ Time Frame: Baseline (Day 1) until Week 48 ]

13.  Primary:

Number of Participants Who Permanently Discontinued the Treatment Due to an AE   [ Time Frame: Baseline (Day 1) until Week 48 ]

14.  Secondary:

Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 4, 12, 24, 36, and 48 (MSD=F)   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

15.  Secondary:

Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 4, 12, 24, 36, and 48 (Observed Analysis)   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

16.  Secondary:

Median Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 4, 12, 24, 36, and 48 (Observed Analysis)   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

17.  Secondary:

Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 4, 12, 24, 36, and 48 (MSD=F Analysis)   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

18.  Secondary:

Median Percent Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 4, 12, 24, 36, and 48   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

19.  Secondary:

Median Percent Change From Baseline in CD4+ Cell Count at Weeks 4, 12, 24, 36, and 48   [ Time Frame: Baseline and Weeks 4, 12, 24, 36, and 48 ]

20.  Secondary:

Number of Participants With the Indicated Virological Outcome at Week 48   [ Time Frame: Week 48 ]

21.  Secondary:

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

22.  Secondary:

Plasma RTV Cmax   [ Time Frame: Week 48 ]

23.  Secondary:

Plasma RTV Cτ   [ Time Frame: Week 48 ]

24.  Secondary:

Plasma RTV CL/F Expressed in mL/Min/kg   [ Time Frame: Week 48 ]

25.  Secondary:

Plasma RTV CL/F Expressed in mL/Min   [ Time Frame: Week 48 ]

26.  Secondary:

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

27.  Secondary:

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

28.  Secondary:

Number of Participants Reporting Perfect Adherence Over the 3 Days and Last Weekend Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by the Study Coordinator Using the Adherence Questionnaire   [ Time Frame: Weeks 2, 12, 24, and 48 ]

29.  Secondary:

Number of Participants With the Indicated Response Scores for the Parent/Guardian (P/G) Perception of FPV Oral Suspension Questionnaire: Items 1 to 4   [ Time Frame: Weeks 2, 24, and 48/premature study discontinuation ]

30.  Secondary:

Number of Participants With the Indicated Response Scores for the Parent/Guardian Perception of the Child’s Assessment of FPV Oral Suspension Questionnaire: Items (I) 5 to 10   [ Time Frame: Weeks (W) 2, 24, and 48/premature study discontinuation ]

31.  Secondary:

Correlation Between Steady-state Plasma APV PK Parameters to Changes in Plasma HIV-1 RNA Concentrations, CD4+ Percentages, and/or the Occurrence of Adverse Events   [ Time Frame: Week 48 ]

32.  Secondary:

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

33.  Secondary:

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

34.  Secondary:

Plasma FPV CL/F Expressed in mL/Min/kg   [ Time Frame: Week 48 ]

35.  Secondary:

Plasma FPV CL/F Expressed in mL/Min   [ Time Frame: Week 48 ]