Trial Outcomes & Findings for A Clinical Study Of An Investigational Regimen Including Marketed HIV Drugs In HIV-1 Pediatric Subjects Ages 2-18 Years (NCT NCT00040664)

NCT ID: NCT00040664

Last Updated: 2017-03-03

Results Overview

The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 69 participants
• Primary outcome timeframe: Baseline through end of study (at least Week 168)
• Results posted on: 2017-03-03

Participant Flow

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

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).

Participant milestones

Measure	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
Overall Study STARTED	69	17	17	35
Overall Study COMPLETED	16	4	4	8
Overall Study NOT COMPLETED	53	13	13	27

Reasons for withdrawal

Measure	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
Overall Study Adverse Event	12	3	2	7
Overall Study Lack of Efficacy	9	2	3	4
Overall Study Insufficient CD4 response	1	0	1	0
Overall Study Lost to Follow-up	4	2	0	2
Overall Study Protocol Violation	2	1	0	1
Overall Study Withdrawal by Subject	7	0	3	4
Overall Study Pregnancy	3	0	0	3
Overall Study Medication adherence/compliance problems	8	2	1	5
Overall Study Poor taste	2	0	2	0
Overall Study Pharmacokinetic target not achieved	2	1	0	1
Overall Study Change of formulation	2	2	0	0
Overall Study Non-viability of oral suspension	1	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	FPV/RTV n=69 Participants 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)
Age, Continuous	10.2 years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	35 participants n=5 Participants
Race/Ethnicity, Customized Black	24 participants n=5 Participants
Race/Ethnicity, Customized East and South East Asian	1 participants n=5 Participants
Race/Ethnicity, Customized American Hispanic	8 participants n=5 Participants
Race/Ethnicity, Customized African Heritage	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through end of study (at least Week 168)

Population: Safety Population: all participants with documented evidence of having received at least one dose of study drug

The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.

Outcome measures

Measure	FPV/RTV n=69 Participants 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)	PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)	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
Number of Participants Who Discontinued Treatment Due to Adverse Events Any event	12 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Nausea	3 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Vomiting	3 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Stomach discomfort	1 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Hyperglycaemia	1 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Hypertriglyceridaemia	1 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Hodgkin's disease	1 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Haemoptysis	1 Participants	—	—	—
Number of Participants Who Discontinued Treatment Due to Adverse Events Blood alkaline phosphatase increased	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Baseline through end of study (at least Week 168)

Population: Safety Population: all participants with documented evidence of having received at least one dose of study drug

The number of participants with drug-related adverse events coded as Grade 2 (mild), Grade 3 (severe), or Grade 4 (life-threatening).

Outcome measures

Measure	FPV/RTV n=24 Participants 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)	PI-Experienced n=45 Participants Participants treated with equal to or less than 3 PIs (any length of time)	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
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event All Grade 2-4 events	7 Participants	14 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Vomiting	0 Participants	5 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Diarrhea	2 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Nausea	2 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Blood alkaline phosphatase increased	1 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Blood triglycerides increased	1 Participants	0 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Abdominal pain	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Benign salivary gland neoplasm	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Blood cholesterol increased	1 Participants	0 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Eosinophil count increased	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Hemoptysis	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Hyperglycemia	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Hypertrichosis	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Lipodystrophy acquired	1 Participants	0 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Lipohypertrophy	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Rash	0 Participants	1 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Somnolence	1 Participants	0 Participants	—	—
Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event Stomach discomfort	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline through end of study (at least Week 168)

Population: Safety Population: all participants with documented evidence of having received at least one dose of study drug

The number of participants with Grade 3 (severe) or Grade 4 (life-threatening) laboratory abnormalities while on study treatment.

Outcome measures

Measure	FPV/RTV n=69 Participants 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)	PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)	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
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities All parameters	6 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Alanine aminotransferase	2 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Aspartate aminotransferase	3 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Cholesterol	0 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Hyperglycemia	0 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Hypoglycemia	0 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Serum lipase	0 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Triglycerides	1 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Leucopenia	1 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Neutropenia	12 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Thrombocytopenia	2 Participants	—	—	—
Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities Anemia	1 Participants	—	—	—

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)	47.3 hours*micrograms/milliliter Interval 34.2 to 65.4	47.6 hours*micrograms/milliliter Interval 27.0 to 84.0	75.5 hours*micrograms/milliliter Interval 23.4 to 244.0	71.8 hours*micrograms/milliliter Interval 10.6 to 486.0

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Geometric Mean of Steady State Plasma APV Parameter: Cmax	4.97 micrograms/milliliter Interval 3.76 to 6.58	5.07 micrograms/milliliter Interval 2.5 to 10.3	6.88 micrograms/milliliter Interval 4.31 to 11.0	7.70 micrograms/milliliter Interval 2.7 to 21.9

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

tmax: time after administration of the drug when maximum concentration is reached

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Median Steady State Plasma APV Tmax	1.04 hours Interval 0.95 to 4.02	1.12 hours Interval 0.75 to 2.07	1.08 hours Interval 0.92 to 2.0	3.78 hours Interval 1.0 to 4.0

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Geometric Mean of Steady State Plasma APV Parameter: CL/F	10.5 milliliters/minute/kilogram Interval 7.62 to 14.5	10.6 milliliters/minute/kilogram Interval 6.09 to 18.5	6.57 milliliters/minute/kilogram Interval 2.08 to 20.7	4.95 milliliters/minute/kilogram Interval 0.745 to 32.9

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=3 Participants 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)	PI-Experienced Participants treated with equal to or less than 3 PIs (any length of time)	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
Geometric Mean of Steady State Plasma APV Parameter: CL/F	278 milliliters/minute Interval 41.2 to 1882.0	—	—	—

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Geometric Mean of Steady State Plasma APV Parameter: t1/2	17.5 hours Interval 11.1 to 27.7	13.6 hours Interval 9.02 to 20.4	15.0 hours Interval 7.93 to 28.2	14.9 hours Interval 4.78 to 46.4

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Least Squares Mean of Plasma APV Parameter: AUC0-tau	0.695 hours*micrograms/milliliters Interval 0.578 to 0.835	0.699 hours*micrograms/milliliters Interval 0.577 to 0.848	1.11 hours*micrograms/milliliters Interval 0.8 to 1.54	1.06 hours*micrograms/milliliters Interval 0.761 to 1.47

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Least Squares Mean of Plasma APV Parameter: Cmax	0.663 micrograms/milliliters Interval 0.555 to 0.791	0.676 micrograms/milliliters Interval 0.56 to 0.814	0.917 micrograms/milliliters Interval 0.667 to 1.26	1.03 micrograms/milliliters Interval 0.747 to 1.41

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=10 Participants 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)	PI-Experienced n=9 Participants Participants treated with equal to or less than 3 PIs (any length of time)	FPV/RTV 30/6 mg/kg Once Daily (Suspension), 12-18 Years n=3 Participants FPV/RTV 30/6 mg/kg once daily (suspension), 12-18 years	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years n=3 Participants FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Least Squares Mean of Plasma APV Parameter: Ctau	0.716 microgram per milliliter Interval 0.548 to 0.936	0.837 microgram per milliliter Interval 0.663 to 1.06	0.963 microgram per milliliter Interval 0.696 to 1.33	0.706 microgram per milliliter Interval 0.568 to 0.878

SECONDARY outcome

Timeframe: Weeks 12, 48, 96, and 168

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=32 Participants 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)	PI-Experienced n=37 Participants Participants treated with equal to or less than 3 PIs (any length of time)	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
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) Week 12	22 percentage of participants	20 percentage of participants	—	—
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) Week 48	16 percentage of participants	16 percentage of participants	—	—
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) Week 96	13 percentage of participants	11 percentage of participants	—	—
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) Week 168	11 percentage of participants	7 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 48, 96, and 168

Population: ITT-E Population. Results are stratified by previous PI experience. Participants with previous PI experience may respond differently to FPV.

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.

Outcome measures

Measure	FPV/RTV n=32 Participants 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)	PI-Experienced n=37 Participants Participants treated with equal to or less than 3 PIs (any length of time)	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
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits Week 12	-2.85 log10 copies/mL Interval -3.12 to -2.54	-2.03 log10 copies/mL Interval -3.02 to -0.64	—	—
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits Week 48	-2.65 log10 copies/mL Interval -3.31 to -1.44	-1.65 log10 copies/mL Interval -2.76 to -1.02	—	—
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits Week 96	-2.52 log10 copies/mL Interval -3.14 to -1.42	-1.76 log10 copies/mL Interval -2.91 to -0.57	—	—
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits Week 168	-2.88 log10 copies/mL Interval -3.49 to -2.15	-2.39 log10 copies/mL Interval -3.13 to -0.94	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 48, 96, and 168

Population: ITT-E Population. Results are stratified by previous PI experience. Participants with previous PI experience may respond differently to FPV.

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.

Outcome measures

Measure	FPV/RTV n=32 Participants 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)	PI-Experienced n=37 Participants Participants treated with equal to or less than 3 PIs (any length of time)	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
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits Week 12	95 Cells/mm3 Interval 10.0 to 150.0	40 Cells/mm3 Interval -30.0 to 110.0	—	—
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits Week 48	150 Cells/mm3 Interval 75.0 to 280.0	120 Cells/mm3 Interval 0.0 to 240.0	—	—
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits Week 96	160 Cells/mm3 Interval 55.0 to 280.0	40 Cells/mm3 Interval -180.0 to 180.0	—	—
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits Week 168	180 Cells/mm3 Interval 10.0 to 430.0	0 Cells/mm3 Interval -220.0 to 200.0	—	—

SECONDARY outcome

Timeframe: Time of virologic failure

Population: 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.

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.

Outcome measures

Measure	FPV/RTV n=32 Participants 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)	PI-Experienced n=37 Participants Participants treated with equal to or less than 3 PIs (any length of time)	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
Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline	2 Participants	2 Participants	—	—

Adverse Events

FPV/RTV

Serious events: 19 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	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)
Immune system disorders Drug hypersensitivity	4.3% 3/69
Infections and infestations Measles	2.9% 2/69
General disorders Pyrexia	2.9% 2/69
Infections and infestations Appendicitis	1.4% 1/69
Infections and infestations Gastroenteritis	1.4% 1/69
Infections and infestations Pneumonia	1.4% 1/69
Infections and infestations Pneumonia bacterial	1.4% 1/69
Psychiatric disorders Aggression	1.4% 1/69
Psychiatric disorders Anxiety	1.4% 1/69
Psychiatric disorders Bipolar disorder	1.4% 1/69
Psychiatric disorders Borderline personality disorder	1.4% 1/69
Psychiatric disorders Depression	1.4% 1/69
Psychiatric disorders Impulse control disorder	1.4% 1/69
Blood and lymphatic system disorders Anemia	1.4% 1/69
Hepatobiliary disorders Hepatitis	1.4% 1/69
Injury, poisoning and procedural complications Eye penetration	1.4% 1/69
Investigations Blood alkaline phosphatase increased	1.4% 1/69
Metabolism and nutrition disorders Hyperglycemia	1.4% 1/69
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	1.4% 1/69
Nervous system disorders Headache	1.4% 1/69
Respiratory, thoracic and mediastinal disorders Hemoptysis	1.4% 1/69

Other adverse events

Measure	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)
Gastrointestinal disorders Vomiting	40.6% 28/69
Gastrointestinal disorders Diarrhoea	26.1% 18/69
Gastrointestinal disorders Nausea	23.2% 16/69
Gastrointestinal disorders Abdominal pain	10.1% 7/69
Gastrointestinal disorders Abdominal pain upper	5.8% 4/69
Gastrointestinal disorders Dental caries	5.8% 4/69
Infections and infestations Upper respiratory tract infection	24.6% 17/69
Infections and infestations Bronchitis	17.4% 12/69
Infections and infestations Nasopharyngitis	15.9% 11/69
Infections and infestations Otitis media	11.6% 8/69
Infections and infestations Influenza	8.7% 6/69
Infections and infestations Oral herpes	5.8% 4/69
Infections and infestations Pharyngitis	5.8% 4/69
Infections and infestations Pharyngitis streptococcal	5.8% 4/69
Infections and infestations Sinusitis	5.8% 4/69
Respiratory, thoracic and mediastinal disorders Cough	23.2% 16/69
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.7% 6/69
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	7.2% 5/69
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.2% 5/69
Respiratory, thoracic and mediastinal disorders Epistaxis	5.8% 4/69
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	5.8% 4/69
Skin and subcutaneous tissue disorders Rash	14.5% 10/69
Skin and subcutaneous tissue disorders Acne	5.8% 4/69
General disorders Pyrexia	14.5% 10/69
Nervous system disorders Headache	24.6% 17/69
Injury, poisoning and procedural complications Arthropod bite	5.8% 4/69
Blood and lymphatic system disorders Lymphadenopathy	5.8% 4/69
Eye disorders Conjunctivitis	5.8% 4/69
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	5.8% 4/69

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER