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

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/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.

Baseline Measures

	FPV/RTV BID
Overall Participants Analyzed  [Units: Participants]	54
Age  [Units: Months] Mean (Standard Deviation)	8.6  (6.43)
Gender  [Units: Participants] Count of Participants
Female	31  57.4%
Male	23  42.6%
Race/Ethnicity, Customized  [Units: Participants]
Black	44
White/Caucasian	2
American Indian	8

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 ]

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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