A Clinical Study Of An Investigational Regimen Including Marketed HIV Drugs In HIV-1 Pediatric Subjects Ages 2-18 Years

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00040664
First received: July 5, 2002
Last updated: January 24, 2011
Last verified: January 2011
Results First Received: August 6, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: ritonavir
Drug: fosamprenavir

  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
Cohorts were recruited in parallel. All Age Cohorts were given the same treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The overall study population consisted of 69 participants presented as "Overall Fosamprenavir (FPV)/ritonavir (RTV)" in the Participant Flow section. Furthermore, the Overall FPV/RTV participants are stratified by age cohorts (Arms 2-4).

Reporting Groups
  Description
Overall Fosamprenavir (FPV)/Ritonavir(RTV) Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)
2-5 Years FPV/RTV Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD), 2-5 years
6-11 Years FPV/RTV Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD), 6-11 years
12-18 Years FPV/RTV Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD), 12-18 years

Participant Flow:   Overall Study
    Overall Fosamprenavir (FPV)/Ritonavir(RTV)     2-5 Years FPV/RTV     6-11 Years FPV/RTV     12-18 Years FPV/RTV  
STARTED     69 [1]   17     17     35  
COMPLETED     16     4     4     8  
NOT COMPLETED     53     13     13     27  
Adverse Event                 12                 3                 2                 7  
Lack of Efficacy                 9                 2                 3                 4  
Insufficient CD4 response                 1                 0                 1                 0  
Lost to Follow-up                 4                 2                 0                 2  
Protocol Violation                 2                 1                 0                 1  
Withdrawal by Subject                 7                 0                 3                 4  
Pregnancy                 3                 0                 0                 3  
Medication adherence/compliance problems                 8                 2                 1                 5  
Poor taste                 2                 0                 2                 0  
Pharmacokinetic target not achieved                 2                 1                 0                 1  
Change of formulation                 2                 2                 0                 0  
Non-viability of oral suspension                 1                 0                 1                 0  
[1] All (69) enrolled on QD; 10 switched to twice daily. Participant flow not collected for this group.



  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 Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Baseline Measures
    FPV/RTV  
Number of Participants  
[units: participants]
  69  
Age  
[units: years]
Mean ± Standard Deviation
  10.2  ± 4.6  
Gender  
[units: participants]
 
Female     39  
Male     30  
Race/Ethnicity, Customized  
[units: participants]
 
White/Caucasian     35  
Black     24  
East and South East Asian     1  
American Hispanic     8  
African Heritage     1  



  Outcome Measures
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1.  Primary:   Number of Participants Who Discontinued Treatment Due to Adverse Events   [ Time Frame: Baseline through end of study (at least Week 168) ]

Measure Type Primary
Measure Title Number of Participants Who Discontinued Treatment Due to Adverse Events
Measure Description The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.
Time Frame Baseline through end of study (at least Week 168)  
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: all participants with documented evidence of having received at least one dose of study drug

Reporting Groups
  Description
FPV/RTV Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Measured Values
    FPV/RTV  
Number of Participants Analyzed  
[units: participants]
  69  
Number of Participants Who Discontinued Treatment Due to Adverse Events  
[units: Participants]
 
Any event     12  
Nausea     3  
Vomiting     3  
Stomach discomfort     1  
Hyperglycaemia     1  
Hypertriglyceridaemia     1  
Blood alkaline phosphatase increased     1  
Hodgkin's disease     1  
Haemoptysis     1  

No statistical analysis provided for Number of Participants Who Discontinued Treatment Due to Adverse Events



2.  Primary:   Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event   [ Time Frame: Baseline through end of study (at least Week 168) ]

Measure Type Primary
Measure Title Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event
Measure Description The number of participants with drug-related adverse events coded as Grade 2 (mild), Grade 3 (severe), or Grade 4 (life-threatening).
Time Frame Baseline through end of study (at least Week 168)  
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: all participants with documented evidence of having received at least one dose of study drug

Reporting Groups
  Description
FPV Tablet Fosamprenavir 700 mg tablets/ritonavir 100 mg capsules once daily
FPV Oral Suspension Fosamprenavir 50 mg/mL oral suspension/ritonavir 80 mg/mL oral solution once daily

Measured Values
    FPV Tablet     FPV Oral Suspension  
Number of Participants Analyzed  
[units: participants]
  24     45  
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event  
[units: Participants]
   
All Grade 2-4 events     7     14  
Vomiting     0     5  
Diarrhea     2     1  
Nausea     2     1  
Blood alkaline phosphatase increased     1     1  
Blood triglycerides increased     1     0  
Abdominal pain     0     1  
Benign salivary gland neoplasm     0     1  
Blood cholesterol increased     1     0  
Eosinophil count increased     0     1  
Hemoptysis     0     1  
Hyperglycemia     0     1  
Hypertrichosis     0     1  
Lipodystrophy acquired     1     0  
Lipohypertrophy     0     1  
Rash     0     1  
Somnolence     1     0  
Stomach discomfort     1     0  

No statistical analysis provided for Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event



3.  Primary:   Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities   [ Time Frame: Baseline through end of study (at least Week 168) ]

Measure Type Primary
Measure Title Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities
Measure Description The number of participants with Grade 3 (severe) or Grade 4 (life-threatening) laboratory abnormalities while on study treatment.
Time Frame Baseline through end of study (at least Week 168)  
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: all participants with documented evidence of having received at least one dose of study drug

Reporting Groups
  Description
FPV/RTV Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Measured Values
    FPV/RTV  
Number of Participants Analyzed  
[units: participants]
  69  
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities  
[units: Participants]
 
All parameters     6  
Alanine aminotransferase     2  
Aspartate aminotransferase     3  
Cholesterol     0  
Hyperglycemia     0  
Hypoglycemia     0  
Serum lipase     0  
Triglycerides     1  
Leucopenia     1  
Neutropenia     12  
Thrombocytopenia     2  
Anemia     1  

No statistical analysis provided for Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities



4.  Primary:   Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)
Measure Description Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. AUC(0-tau)=area under the concentration curve from time 0 to tau.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The Pharmacokinetic (PK) Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)  
[units: hours*micrograms/milliliter]
Geometric Mean ( 95% Confidence Interval )
  47.3  
  ( 34.2 to 65.4 )  
  47.6  
  ( 27.0 to 84.0 )  
  75.5  
  ( 23.4 to 244 )  
  71.8  
  ( 10.6 to 486 )  

No statistical analysis provided for Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)



5.  Primary:   Geometric Mean of Steady State Plasma APV Parameter: Cmax   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Geometric Mean of Steady State Plasma APV Parameter: Cmax
Measure Description Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. Cmax= concentration maximum.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Geometric Mean of Steady State Plasma APV Parameter: Cmax  
[units: micrograms/milliliter]
Geometric Mean ( 95% Confidence Interval )
  4.97  
  ( 3.76 to 6.58 )  
  5.07  
  ( 2.50 to 10.3 )  
  6.88  
  ( 4.31 to 11.0 )  
  7.70  
  ( 2.70 to 21.9 )  

No statistical analysis provided for Geometric Mean of Steady State Plasma APV Parameter: Cmax



6.  Primary:   Median Steady State Plasma APV Tmax   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Median Steady State Plasma APV Tmax
Measure Description tmax: time after administration of the drug when maximum concentration is reached
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Median Steady State Plasma APV Tmax  
[units: hours]
Median ( Full Range )
  1.04  
  ( 0.95 to 4.02 )  
  1.12  
  ( 0.75 to 2.07 )  
  1.08  
  ( 0.92 to 2.00 )  
  3.78  
  ( 1.00 to 4.00 )  

No statistical analysis provided for Median Steady State Plasma APV Tmax



7.  Primary:   Geometric Mean of Steady State Plasma APV Parameter: CL/F   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Geometric Mean of Steady State Plasma APV Parameter: CL/F
Measure Description Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. CL/F=apparent plasma clearance.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years vs. Historical Adult Data
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years vs. Historical Adult Data

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Geometric Mean of Steady State Plasma APV Parameter: CL/F  
[units: milliliters/minute/kilogram]
Geometric Mean ( 95% Confidence Interval )
  10.5  
  ( 7.62 to 14.5 )  
  10.6  
  ( 6.09 to 18.5 )  
  6.57  
  ( 2.08 to 20.7 )  
  4.95  
  ( 0.745 to 32.9 )  

No statistical analysis provided for Geometric Mean of Steady State Plasma APV Parameter: CL/F



8.  Primary:   Geometric Mean of Steady State Plasma APV Parameter: CL/F   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Geometric Mean of Steady State Plasma APV Parameter: CL/F
Measure Description Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. CL/F=apparent plasma clearance.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  3  
Geometric Mean of Steady State Plasma APV Parameter: CL/F  
[units: milliliters/minute]
Geometric Mean ( 95% Confidence Interval )
  278  
  ( 41.2 to 1882 )  

No statistical analysis provided for Geometric Mean of Steady State Plasma APV Parameter: CL/F



9.  Primary:   Geometric Mean of Steady State Plasma APV Parameter: t1/2   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Geometric Mean of Steady State Plasma APV Parameter: t1/2
Measure Description Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. t1/2=elimination half-life. t1/2=elimination half-life.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Geometric Mean of Steady State Plasma APV Parameter: t1/2  
[units: hours]
Geometric Mean ( 95% Confidence Interval )
  17.5  
  ( 11.1 to 27.7 )  
  13.6  
  ( 9.02 to 20.4 )  
  15.0  
  ( 7.93 to 28.2 )  
  14.9  
  ( 4.78 to 46.4 )  

No statistical analysis provided for Geometric Mean of Steady State Plasma APV Parameter: t1/2



10.  Primary:   Least Squares Mean of Plasma APV Parameter: AUC0-tau   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]

Measure Type Primary
Measure Title Least Squares Mean of Plasma APV Parameter: AUC0-tau
Measure Description A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years vs. Historical Adult Data
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years vs. Historical Adult Data

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Least Squares Mean of Plasma APV Parameter: AUC0-tau  
[units: hours*micrograms/milliliters]
Least Squares Mean ( 95% Confidence Interval )
  0.695  
  ( 0.578 to 0.835 )  
  0.699  
  ( 0.577 to 0.848 )  
  1.11  
  ( 0.800 to 1.54 )  
  1.06  
  ( 0.761 to 1.47 )  

No statistical analysis provided for Least Squares Mean of Plasma APV Parameter: AUC0-tau



11.  Primary:   Least Squares Mean of Plasma APV Parameter: Cmax   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4. ]

Measure Type Primary
Measure Title Least Squares Mean of Plasma APV Parameter: Cmax
Measure Description A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years vs. Historical Adult Data
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years vs. Historical Adult Data
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years vs. Historical Adult Data

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Least Squares Mean of Plasma APV Parameter: Cmax  
[units: micrograms/milliliters]
Least Squares Mean ( 95% Confidence Interval )
  0.663  
  ( 0.555 to 0.791 )  
  0.676  
  ( 0.560 to 0.814 )  
  0.917  
  ( 0.667 to 1.26 )  
  1.03  
  ( 0.747 to 1.41 )  

No statistical analysis provided for Least Squares Mean of Plasma APV Parameter: Cmax



12.  Primary:   Least Squares Mean of Plasma APV Parameter: Ctau   [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4. ]

Measure Type Primary
Measure Title Least Squares Mean of Plasma APV Parameter: Ctau
Measure Description A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.
Time Frame 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.  
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.
The PK Parameter Population included all participants who underwent plasma PK sampling and provided full PK profiles with evaluable plasma APV PK parameter data; thus, the sample sizes were limited. Results are stratified by age cohort and formulation since these factors can impact PK profiles.

Reporting Groups
  Description
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years FPV/RTV 30/6 mg/kg once daily (suspension), 2-5 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years FPV/RTV 30/6 mg/kg once daily (suspension), 6-11 years
FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years
FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years FPV/RTV 1400/200 mg once daily (tablet), 12-18 years

Measured Values
    FPV/RTV 30/6 mg/kg Once Daily (Suspension), 2-5 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 6-11 Years     FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years     FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years  
Number of Participants Analyzed  
[units: participants]
  10     9     3     3  
Least Squares Mean of Plasma APV Parameter: Ctau  
[units: microgram per milliliter]
Least Squares Mean ( 95% Confidence Interval )
  0.716  
  ( 0.548 to 0.936 )  
  0.837  
  ( 0.663 to 1.06 )  
  0.963  
  ( 0.696 to 1.33 )  
  0.706  
  ( 0.568 to 0.878 )  

No statistical analysis provided for Least Squares Mean of Plasma APV Parameter: Ctau



13.  Secondary:   Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis)   [ Time Frame: Weeks 12, 48, 96, and 168 ]

Measure Type Secondary
Measure Title Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis)
Measure Description A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies per milliliter (mL) at Weeks 12, 48, 96, and 196. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 12, 48, 96, 168 was determined by the TLOVR algorithm with stratification by the six randomization strata. TLOVR analysis categorizes participants by treatment response. Responders were participants with confirmed viral load <400copies/mL on two consecutive visits.
Time Frame Weeks 12, 48, 96, and 168  
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.
The Intent-to-Treat Exposed (ITT [E]) Population consisted of all subjects with documented evidence of having received at least one dose of study drug. Results are stratified by previous protease inhibitor (PI) experience. Participants with previous PI experience may respond differently to FPV.

Reporting Groups
  Description
PI-Naive Participants with equal to or less than 1 week of treatment with a Protease Inhibitor (PI)
PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)

Measured Values
    PI-Naive     PI-Experienced  
Number of Participants Analyzed  
[units: participants]
  32     37  
Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis)  
[units: percentage of participants]
   
Week 12     22     20  
Week 48     16     16  
Week 96     13     11  
Week 168     11     7  

No statistical analysis provided for Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis)



14.  Secondary:   Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits   [ Time Frame: Baseline and Weeks 12, 48, 96, and 168 ]

Measure Type Secondary
Measure Title Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits
Measure Description A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 12, 24, 48, 96, and 168. Change from Baseline was defined as the HIV-1 RNA level at Weeks 12, 24, 48, 96, and 168 minus the HIV-1 RNA level at Baseline.
Time Frame Baseline and Weeks 12, 48, 96, and 168  
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.
ITT-E Population. Results are stratified by previous PI experience. Participants with previous PI experience may respond differently to FPV.

Reporting Groups
  Description
PI-Naive Participants with equal to or less than 1 week of treatment with a Protease Inhibitor (PI)
PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)

Measured Values
    PI-Naive     PI-Experienced  
Number of Participants Analyzed  
[units: participants]
  32     37  
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits  
[units: log10 copies/mL]
Median ( Inter-Quartile Range )
   
Week 12     -2.85  
  ( -3.12 to -2.54 )  
  -2.03  
  ( -3.02 to -0.64 )  
Week 48     -2.65  
  ( -3.31 to -1.44 )  
  -1.65  
  ( -2.76 to -1.02 )  
Week 96     -2.52  
  ( -3.14 to -1.42 )  
  -1.76  
  ( -2.91 to -0.57 )  
Week 168     -2.88  
  ( -3.49 to -2.15 )  
  -2.39  
  ( -3.13 to -0.94 )  

No statistical analysis provided for Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits



15.  Secondary:   Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits   [ Time Frame: Baseline and Weeks 12, 48, 96, and 168 ]

Measure Type Secondary
Measure Title Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits
Measure Description A blood sample was drawn to determine the CD4+ cell count at Weeks 24, 48, 96, and 168. Change from Baseline was defined as the CD4+ cell count at Weeks 24, 48, 96, and 168 minus the CD4+ cell count at Baseline.
Time Frame Baseline and Weeks 12, 48, 96, and 168  
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.
ITT-E Population. Results are stratified by previous PI experience. Participants with previous PI experience may respond differently to FPV.

Reporting Groups
  Description
PI-Naive Participants with equal to or less than 1 week of treatment with a PI
PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)

Measured Values
    PI-Naive     PI-Experienced  
Number of Participants Analyzed  
[units: participants]
  32     37  
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits  
[units: Cells/mm3]
Median ( Inter-Quartile Range )
   
Week 12     95  
  ( 10 to 150 )  
  40  
  ( -30 to 110 )  
Week 48     150  
  ( 75 to 280 )  
  120  
  ( 0 to 240 )  
Week 96     160  
  ( 55 to 280 )  
  40  
  ( -180 to 180 )  
Week 168     180  
  ( 10 to 430 )  
  0  
  ( -220 to 200 )  

No statistical analysis provided for Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits



16.  Secondary:   Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline   [ Time Frame: Time of virologic failure ]

Measure Type Secondary
Measure Title Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline
Measure Description A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of virologic failure were tabulated by drug class. Virologic failure is defined as HIV-1 RNA greater than or equal to 400 copies/mL.
Time Frame Time of virologic failure  
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.
Participants in the ITT-E Population who met the virologic failure definition. Results are stratified by previous PI experience. Participants with previous PI experience may respond differently to FPV.

Reporting Groups
  Description
PI-Naive Participants with equal to or less than 1 week of treatment with a PI
PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)

Measured Values
    PI-Naive     PI-Experienced  
Number of Participants Analyzed  
[units: participants]
  32     37  
Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline  
[units: Participants]
  2     2  

No statistical analysis provided for Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline




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  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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