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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00071760
First received: October 30, 2003
Last updated: May 8, 2014
Last verified: May 2014
Results First Received: March 2, 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
Interventions: Drug: 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
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  



  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/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  
Number of Participants  
[units: participants]
  54  
Age  
[units: Months]
Mean ± Standard Deviation
  8.6  ± 6.43  
Gender  
[units: Participants]
 
Female     31  
Male     23  
Race/Ethnicity, Customized  
[units: participants]
 
Black     44  
White/Caucasian     2  
American Indian     8  



  Outcome Measures
  Show All Outcome Measures

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 ]
  Hide Outcome Measure 11

Measure Type Primary
Measure Title Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities
Measure Description TE toxicities were presented for each laboratory parameter. A toxicity was considered TE if it was greater than the Baseline grade, and if it was observed on/after the date of the first dose of study drug (SD), and on/before the date of the last dose of SD. Neutropenia is a decrease (d) in the number of Ns, d/increase (I) in glucose is hypo (Hp)/hyper (Hy)glycemia, in potassium is Hp/Hykalemia, and in sodium is Hp/Hynatremia. Per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Grade 3=severe; Grade 4=potentially life-threatening.
Time Frame Baseline (Day 1) until 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.
Safety Population. Only those participants contributing data were analyzed.

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.

Measured Values
    FPV/RTV BID  
Number of Participants Analyzed  
[units: participants]
  51  
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities  
[units: participants]
 
ALT >5.0x upper limit of normal (ULN); n=51     3  
AST >5.0x ULN; n=51     0  
Cholesterol >7.77 millimoles/liter (mmol/L); n=49     0  
Lipase increased >3.0x ULN; n=10     0  
Hypoglycemia <2.22 mmol/L; n=51     0  
Hyperglycemia >13.88 mmol/L; n=51     0  
Hemoglobin <1.16 mmol/L; n=51     1  
Platelet count <50.000x10^9/L; n=51     0  
Albumin <20 grams (g)/L; n=51     0  
Alkaline Phosphatase >5.0x ULN; n=51     4  
Creatine Kinase >=10x ULN; n=51     3  
Hyperkalemia >6.5 mmol/L; n=51     0  
Hypokalemia <2.5 mmol/L; n=51     0  
Hypernatremia >=155 mmol/L; n=51     0  
Hyponatremia <125 mmol/L; n=51     0  
Total Neutrophils (Ns) <0.750x10^9/L; n=51     5  

No statistical analysis provided for Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities



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 ]


  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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  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.


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: NCT00071760     History of Changes
Other Study ID Numbers: APV20002
Study First Received: October 30, 2003
Results First Received: March 2, 2012
Last Updated: May 8, 2014
Health Authority: Spain: Spanish Agency of Medicines
United States: Food and Drug Administration