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

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00040664
• Collaborator: (none)
• Enrollment: 69
• Locations: 42
• Arms: 3
• Duration (Months): 75
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a 48-week study to collect additional information on the safety, tolerability, pharmacokinetics, and antiviral activity of an investigational regimen (course of therapy) including FDA approved HIV drugs in HIV-infected patients 2 - 18 years old.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Drug: ritonavir; Drug: fosamprenavir	Phase 2

Detailed Description

A 48 Week, Phase II, Open-label, Multi-Cohort, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GW433908/Ritonavir QD and GW433908/Ritonavir BID when Administered to HIV-1 Infected, Antiretroviral Naive and Experience Pediatric Subjects 2 to 18 Years Old

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 48 Week, Phase II, Open-Label Multi-Cohort, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GW433908/Ritonavir QD and GW433908/Ritonavir BID When Administered to HIV-1 Infected, Antiretroviral Naive and Experienced, Pediatric Subjects 2-18 Years Old
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2 to 5 years (FPV/RTV) Two to five years. 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)	Drug: ritonavir; ritonavir oral capsules or oral solution; Other Names: fosamprenavir ; Drug: fosamprenavir; fosamprenavir oral suspension or tablet
Experimental: 6 to 11 years (FPV/RTV) Six to twelve years. 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)	Drug: ritonavir; ritonavir oral capsules or oral solution; Other Names: fosamprenavir ; Drug: fosamprenavir; fosamprenavir oral suspension or tablet
Experimental: 12 to 18 years (FPV/RTV) Twelve to Eighteen years. 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)	Drug: ritonavir; ritonavir oral capsules or oral solution; Other Names: fosamprenavir ; Drug: fosamprenavir; fosamprenavir oral suspension or tablet

Outcome Measures

Primary Outcome Measures

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

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

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

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

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

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

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

   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.

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

   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.

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

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

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

   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.

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

   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.

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

   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.

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

    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.

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

    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.

Secondary Outcome Measures

1. 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) [Weeks 12, 48, 96, and 168]

   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.

2. Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits [Baseline and Weeks 12, 48, 96, and 168]

   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.

3. Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits [Baseline and Weeks 12, 48, 96, and 168]

   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.

4. 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 of virologic failure]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• Inclusion Criteria:

• Male or females 2 to 18 years of age

• A female is eligible to enter and participate in this study if she is of:

• 1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
• 1. child-bearing potential with a negative serum pregnancy test at screen, a negative urine pregnancy test on Day 1 and who agrees to use one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician). Note: hormonal contraceptives are not considered a sufficient form of contraceptive for this study.

• Complete abstinence from intercourse from 2 weeks prior to administration of study drugs, throughout the study and for 2 weeks after discontinuation of all study medications. Should a female subject of childbearing potential decide to become sexually active during the course of the study, she must be counselled and be willing to use one of the methods listed below:

• Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)

• Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion)

• Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year. All subjects participating in this study should be counselled on the practice of safe/safer sex.

• Parent or legal guardian (and subject whenever possible) has the ability to understand and provide written informed consent for the subject to participate in the trial. Verbal witnessed assent must be obtained from the subject whenever possible.

• Screening plasma HIV-1 RNA > or =400copies/mL.

• Subject's who, in the investigator's opinion, and following resistance testing where appropriate, are able to construct an active NRTI backbone regimen consisting of 2 NRTIs.

• Subjects must meet one of the following criteria:

• ART-naïve subjects are defined as having had < 4 weeks (28 days) therapy with an NRTI, no previous therapy with an NNRTI and < 1 week therapy with an HIV PI.

• ART-experienced subjects are defined as having had greater than 4 weeks (28 days) therapy with any NRTI(s) and any length of therapy with any NNRTI(s) and/or a PI. PI-experienced subjects will be eligible if they have previously been treated with < three PIs, excluding AGENERASE. Prior therapy with a RTV boosted PI regimen will be considered as only 1 prior PI as long as the RTV dose was below that recommended for use of RTV as an antiretroviral agent. This specific criterion is not applicable to subjects in screening and/or enrolling after approval of Amendment No. 4. - For subjects screening and/or enrolling after the approval of Amendment No.4, PI naive subjects are defined as ART experienced subjects having less than one week of therapy with a PI and no prior experience with AGENERASE. Prior treatment with NNRTIs and NRTIs is permitted (however, subjects will NOT be permitted to receive concurrent NNRTI therapy while participating in this study)

• Exclusion Criteria:

• Prior history of having received amprenavir.

• Use of non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy within 14 days of study Day 1 or anticipated need for concurrent NNRTI therapy during the study period.

• Have had an AIDS defining illness (acute CDC Category C event) within 28 days of screening.

• Pregnant or lactating.

• Non-nucleoside reverse transcriptase inhibitor therapy within 14 days prior to study drug administration or anticipated need for concurrent NNRTI therapy during the study period.

• Subjects who, in the investigator's opinion, are not able to comply with the requirements of the study.

• An acute CDC Category C event (per 1993/1994 classification) and/or serious bacterial infection(s) within 28 days prior to study drug administration.

• Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the subject unable to take oral medication.

• Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia,diabetes, cardiac dysfunction and hepatitis) which, in the opinion of the investigator, might compromise the safety of the subject.

• Current grade 2 or higher serum lipase within 28 days prior to study drug administration and/or history of clinically relevant pancreatitis within the previous 6 months. - Grade 3 or 4 transaminase levels (ALT and/or AST) within 28 days prior to study drug administration and/or clinically relevant hepatitis within the previous 6 months.

• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days of study drug administration or an anticipated need for such treatment within the study period.

• Treatment with immunomodulating agents (e.g., systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (e.g., hydroxyurea or foscarnet) within 28 days of study drug administration.

• Treatment with any of the following medications within 28 days prior to receiving study medication or the anticipated need during the study:

• Amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepin, dihydroergotamine, encainide, ergonovine, ergotamine, estazolam, flecainide, flurazepam, lovastatin, meperidine, methylergonovine, midazolam, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, simvastatin, terfenadine, triazolam, zolpidem (these drugs have been excluded for safety reasons).

• Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (these drugs have been excluded because they have the potential to decrease plasma protease inhibitor concentrations) - Systemic chemotherapeutic agents

• Treatment with other investigational drugs/therapies (note: treatments available through a Treatment IND or other expanded-access mechanism will be evaluated on a case-by-case basis in consultation with the sponsor) within 28 days prior to study drug administration

• History of drug or other allergy which, in the opinion of the investigator, contraindicates participation in the trial or known hypersensitivity to any study medications (e.g., documented hypersensitivity to a nucleoside analogue).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35233
2	GSK Investigational Site	Los Angeles	California	United States	90027
3	GSK Investigational Site	Jacksonville	Florida	United States	32209
4	GSK Investigational Site	Tampa	Florida	United States	33613
5	GSK Investigational Site	Chicago	Illinois	United States	60614
6	GSK Investigational Site	New Orleans	Louisiana	United States	70112
7	GSK Investigational Site	Boston	Massachusetts	United States	02118
8	GSK Investigational Site	Bronx	New York	United States	10457
9	GSK Investigational Site	New York	New York	United States	10016
10	GSK Investigational Site	New York	New York	United States	10021
11	GSK Investigational Site	Stony Brook	New York	United States	11794-8111
12	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599-7220
13	GSK Investigational Site	Durham	North Carolina	United States	27705
14	GSK Investigational Site	Cleveland	Ohio	United States	44106
15	GSK Investigational Site	Dallas	Texas	United States	75235
16	GSK Investigational Site	Fort Worth	Texas	United States	76104
17	GSK Investigational Site	Richmond	Virginia	United States	23298
18	GSK Investigational Site	Toronto	Ontario	Canada	M5G 1X8
19	GSK Investigational Site	Montreal	Quebec	Canada	H3T 1C5
20	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41150
21	GSK Investigational Site	Roma	Lazio	Italy	00165
22	GSK Investigational Site	Genova	Liguria	Italy	16132
23	GSK Investigational Site	Milano	Lombardia	Italy	20122
24	GSK Investigational Site	Milano	Lombardia	Italy	20142
25	GSK Investigational Site	Pavia	Lombardia	Italy	27100
26	GSK Investigational Site	Firenze	Toscana	Italy	55100
27	GSK Investigational Site	Padova	Veneto	Italy	35128
28	GSK Investigational Site	Rotterdam		Netherlands	3015 GE
29	GSK Investigational Site	Amadora		Portugal	2700
30	GSK Investigational Site	Lisboa		Portugal	1150
31	GSK Investigational Site	Lisboa		Portugal	1649-035
32	GSK Investigational Site	Bucharest		Romania	021105
33	GSK Investigational Site	Bucharest		Romania	030303
34	GSK Investigational Site	Barcelona		Spain	08003
35	GSK Investigational Site	Barcelona		Spain	08035
36	GSK Investigational Site	Barcelona		Spain	08950
37	GSK Investigational Site	Madrid		Spain	28007
38	GSK Investigational Site	Madrid		Spain	28041
39	GSK Investigational Site	Madrid		Spain	28047
40	GSK Investigational Site	Palma de Mallorca		Spain	07014
41	GSK Investigational Site	Sevilla		Spain	41013
42	GSK Investigational Site	Valencia		Spain	46009

Sponsors and Collaborators

• ViiV Healthcare

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT00040664
• Other Study ID Numbers: APV 20003
• First Posted: Jul 10, 2002
• Last Update Posted: Mar 3, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by ViiV Healthcare: pediatrics; HIV; protease inhibitors; ritonavir; fosamprenavir; LEXIVA; AGENERASE; amprenavir
• Additional relevant MeSH terms: HIV Infections; Ritonavir; Fosamprenavir

Study Results

Participant Flow

Recruitment Details	Cohorts were recruited in parallel. All Age Cohorts were given the same treatment.
Pre-assignment Detail	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).

Arm/Group Title	Overall Fosamprenavir (FPV)/Ritonavir(RTV)	2-5 Years FPV/RTV	6-11 Years FPV/RTV	12-18 Years FPV/RTV
Arm/Group Description	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)	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	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	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
Period Title: Overall Study
STARTED	69	17	17	35
COMPLETED	16	4	4	8
NOT COMPLETED	53	13	13	27

Baseline Characteristics

Arm/Group Title	FPV/RTV
Arm/Group Description	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)
Overall Participants	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (4.6)
Sex: Female, Male (Count of Participants)
Female	39 56.5%
Male	30 43.5%
Race/Ethnicity, Customized (participants) [Number]
White/Caucasian	35 50.7%
Black	24 34.8%
East and South East Asian	1 1.4%
American Hispanic	8 11.6%
African Heritage	1 1.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Discontinued Treatment Due to Adverse Events
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FPV/RTV
Arm/Group Description	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)
Measure Participants	69
Any event	12 17.4%
Nausea	3 4.3%
Vomiting	3 4.3%
Stomach discomfort	1 1.4%
Hyperglycaemia	1 1.4%
Hypertriglyceridaemia	1 1.4%
Blood alkaline phosphatase increased	1 1.4%
Hodgkin's disease	1 1.4%
Haemoptysis	1 1.4%

2. Secondary Outcome

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)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PI-Naive	PI-Experienced
Arm/Group Description	Participants with equal to or less than 1 week of treatment with a Protease Inhibitor (PI)	Participants treated with equal to or less than 3 PIs (any length of time)
Measure Participants	32	37
Week 12	22 31.9%	20 NaN
Week 48	16 23.2%	16 NaN
Week 96	13 18.8%	11 NaN
Week 168	11 15.9%	7 NaN

3. Secondary Outcome

Title	Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PI-Naive	PI-Experienced
Arm/Group Description	Participants with equal to or less than 1 week of treatment with a Protease Inhibitor (PI)	Participants treated with equal to or less than 3 PIs (any length of time)
Measure Participants	32	37
Week 12	-2.85	-2.03
Week 48	-2.65	-1.65
Week 96	-2.52	-1.76
Week 168	-2.88	-2.39

4. Secondary Outcome

Title	Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PI-Naive	PI-Experienced
Arm/Group Description	Participants with equal to or less than 1 week of treatment with a PI	Participants treated with equal to or less than 3 PIs (any length of time)
Measure Participants	32	37
Week 12	95	40
Week 48	150	120
Week 96	160	40
Week 168	180	0

5. Primary Outcome

Title	Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FPV Tablet	FPV Oral Suspension
Arm/Group Description	Fosamprenavir 700 mg tablets/ritonavir 100 mg capsules once daily	Fosamprenavir 50 mg/mL oral suspension/ritonavir 80 mg/mL oral solution once daily
Measure Participants	24	45
All Grade 2-4 events	7 10.1%	14 NaN
Vomiting	0 0%	5 NaN
Diarrhea	2 2.9%	1 NaN
Nausea	2 2.9%	1 NaN
Blood alkaline phosphatase increased	1 1.4%	1 NaN
Blood triglycerides increased	1 1.4%	0 NaN
Abdominal pain	0 0%	1 NaN
Benign salivary gland neoplasm	0 0%	1 NaN
Blood cholesterol increased	1 1.4%	0 NaN
Eosinophil count increased	0 0%	1 NaN
Hemoptysis	0 0%	1 NaN
Hyperglycemia	0 0%	1 NaN
Hypertrichosis	0 0%	1 NaN
Lipodystrophy acquired	1 1.4%	0 NaN
Lipohypertrophy	0 0%	1 NaN
Rash	0 0%	1 NaN
Somnolence	1 1.4%	0 NaN
Stomach discomfort	1 1.4%	0 NaN

6. Primary Outcome

Title	Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FPV/RTV
Arm/Group Description	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)
Measure Participants	69
All parameters	6 8.7%
Alanine aminotransferase	2 2.9%
Aspartate aminotransferase	3 4.3%
Cholesterol	0 0%
Hyperglycemia	0 0%
Hypoglycemia	0 0%
Serum lipase	0 0%
Triglycerides	1 1.4%
Leucopenia	1 1.4%
Neutropenia	12 17.4%
Thrombocytopenia	2 2.9%
Anemia	1 1.4%

7. Primary Outcome

Title	Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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
Measure Participants	10	9	3	3
Geometric Mean (95% Confidence Interval) [hours*micrograms/milliliter]	47.3	47.6	75.5	71.8

8. Primary Outcome

Title	Geometric Mean of Steady State Plasma APV Parameter: Cmax
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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
Measure Participants	10	9	3	3
Geometric Mean (95% Confidence Interval) [micrograms/milliliter]	4.97	5.07	6.88	7.70

9. Secondary Outcome

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
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PI-Naive	PI-Experienced
Arm/Group Description	Participants with equal to or less than 1 week of treatment with a PI	Participants treated with equal to or less than 3 PIs (any length of time)
Measure Participants	32	37
Number [Participants]	2 2.9%	2 NaN

10. Primary Outcome

Title	Median Steady State Plasma APV Tmax
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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
Measure Participants	10	9	3	3
Median (Full Range) [hours]	1.04	1.12	1.08	3.78

11. Primary Outcome

Title	Geometric Mean of Steady State Plasma APV Parameter: CL/F
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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 vs. Historical Adult Data	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 vs. Historical Adult Data
Measure Participants	10	9	3	3
Geometric Mean (95% Confidence Interval) [milliliters/minute/kilogram]	10.5	10.6	6.57	4.95

12. Primary Outcome

Title	Geometric Mean of Steady State Plasma APV Parameter: CL/F
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	FPV/RTV 1400/200 mg Once Daily (Tablet), 12-18 Years
Arm/Group Description	FPV/RTV 1400/200 mg once daily (tablet), 12-18 years
Measure Participants	3
Geometric Mean (95% Confidence Interval) [milliliters/minute]	278

13. Primary Outcome

Title	Geometric Mean of Steady State Plasma APV Parameter: t1/2
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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
Measure Participants	10	9	3	3
Geometric Mean (95% Confidence Interval) [hours]	17.5	13.6	15.0	14.9

14. Primary Outcome

Title	Least Squares Mean of Plasma APV Parameter: AUC0-tau
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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 vs. Historical Adult Data	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 vs. Historical Adult Data
Measure Participants	10	9	3	3
Least Squares Mean (95% Confidence Interval) [hours*micrograms/milliliters]	0.695	0.699	1.11	1.06

15. Primary Outcome

Title	Least Squares Mean of Plasma APV Parameter: Cmax
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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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 vs. Historical Adult Data	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 vs. Historical Adult Data
Measure Participants	10	9	3	3
Least Squares Mean (95% Confidence Interval) [micrograms/milliliters]	0.663	0.676	0.917	1.03

16. Primary Outcome

Title	Least Squares Mean of Plasma APV Parameter: Ctau
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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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
Arm/Group Description	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
Measure Participants	10	9	3	3
Least Squares Mean (95% Confidence Interval) [microgram per milliliter]	0.716	0.837	0.963	0.706

Adverse Events

Arm/Group Title	FPV/RTV
Arm/Group Description	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)
All Cause Mortality
	FPV/RTV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FPV/RTV
	Affected / at Risk (%)	# Events
Total	19/ (NaN)
Blood and lymphatic system disorders
Anemia	1/69 (1.4%)
General disorders
Pyrexia	2/69 (2.9%)
Hepatobiliary disorders
Hepatitis	1/69 (1.4%)
Immune system disorders
Drug hypersensitivity	3/69 (4.3%)
Infections and infestations
Measles	2/69 (2.9%)
Appendicitis	1/69 (1.4%)
Gastroenteritis	1/69 (1.4%)
Pneumonia	1/69 (1.4%)
Pneumonia bacterial	1/69 (1.4%)
Injury, poisoning and procedural complications
Eye penetration	1/69 (1.4%)
Investigations
Blood alkaline phosphatase increased	1/69 (1.4%)
Metabolism and nutrition disorders
Hyperglycemia	1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign salivary gland neoplasm	1/69 (1.4%)
Nervous system disorders
Headache	1/69 (1.4%)
Psychiatric disorders
Aggression	1/69 (1.4%)
Anxiety	1/69 (1.4%)
Bipolar disorder	1/69 (1.4%)
Borderline personality disorder	1/69 (1.4%)
Depression	1/69 (1.4%)
Impulse control disorder	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/69 (1.4%)
Other (Not Including Serious) Adverse Events
	FPV/RTV
	Affected / at Risk (%)	# Events
Total	63/ (NaN)
Blood and lymphatic system disorders
Lymphadenopathy	4/69 (5.8%)
Eye disorders
Conjunctivitis	4/69 (5.8%)
Gastrointestinal disorders
Vomiting	28/69 (40.6%)
Diarrhoea	18/69 (26.1%)
Nausea	16/69 (23.2%)
Abdominal pain	7/69 (10.1%)
Abdominal pain upper	4/69 (5.8%)
Dental caries	4/69 (5.8%)
General disorders
Pyrexia	10/69 (14.5%)
Infections and infestations
Upper respiratory tract infection	17/69 (24.6%)
Bronchitis	12/69 (17.4%)
Nasopharyngitis	11/69 (15.9%)
Otitis media	8/69 (11.6%)
Influenza	6/69 (8.7%)
Oral herpes	4/69 (5.8%)
Pharyngitis	4/69 (5.8%)
Pharyngitis streptococcal	4/69 (5.8%)
Sinusitis	4/69 (5.8%)
Injury, poisoning and procedural complications
Arthropod bite	4/69 (5.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	4/69 (5.8%)
Nervous system disorders
Headache	17/69 (24.6%)
Respiratory, thoracic and mediastinal disorders
Cough	16/69 (23.2%)
Nasal congestion	6/69 (8.7%)
Pharyngolaryngeal pain	5/69 (7.2%)
Rhinorrhoea	5/69 (7.2%)
Epistaxis	4/69 (5.8%)
Rhinitis allergic	4/69 (5.8%)
Skin and subcutaneous tissue disorders
Rash	10/69 (14.5%)
Acne	4/69 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.