48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection
Sponsor
ViiV Healthcare (Industry)
Overall Status
Completed
CT.gov ID
NCT00089583
Collaborator
GlaxoSmithKline (Industry)
110
39
2
108
2.8
0
Study Details
Study Description
Brief Summary
This is a 48-week study to collect information on the safety and activity of an investigational medicine in patients, ages 2 to 18 years old, with HIV infection .
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
A 48 Week, Phase II, non-comparative, open-label, multi-cohort, multicenter study to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of GW433908/Ritonavir BID when administered to HIV-1 infected PI-Naive and experienced, Pediatric Subjects 2 to 18 years old and of GW433908 BID Administered to PI-Naive Pediatric subjects 2 to <6 years old
Study Design
Study Type:
Interventional
Actual Enrollment
:
110 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A 48 Week, Phase II, Non-Comparative, Open-label, Multi-Cohort, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GW433908/Ritonavir BID When Administered to HIV-1 Infected, PI-Naïve and Experienced, Pediatric Subjects, 2 to 18 Years Old and of GW433908 BID Administered to PI-Naïve, Pediatric Subjects 2 to < 6 Years Old
Study Start Date
:
Jul 1, 2004
Actual Primary Completion Date
:
Mar 1, 2011
Actual Study Completion Date
:
Jul 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 2 - 18 yrs old (FPV/RTV BID) Cohort 1B - 2 - less than 6yrs old (FPV/RTV BID) Cohort 2 - 6 to less than 12 yrs old (FPV/RTV BID) Cohort 3 - 12 - 18 yrs old (FPV/RTV BID) Cohort 4 - 2 - 18 yrs (FPV/RTV BID) |
Drug: LEXIVA (GW433908)
Fosamprenavir suspension or tablet bid
Drug: Ritonavir
Ritonavir solution bid
Other Names:
|
| Experimental: 2 - less than 6yrs old (FPV BID) Cohort 1A - 2 - less than 6yrs old (FPV BID) |
Drug: LEXIVA (GW433908)
Fosamprenavir suspension or tablet bid
|
Outcome Measures
Primary Outcome Measures
- Plasma Amprenavir (APV) AUC (0-tau[τ]) [Week 48]
Plasma samples were assayed for APV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma APV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method. hr, hour; µg, micrograms; mL, milliliter.
- Plasma APV Cmax [Week 48]
The maximum concentration at steady state (Cmax) was measured.
- Plasma APV Cτ [Week 48]
The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured.
- Plasma APV CL/F Following Dosing Expressed in mg/kg [Week 48]
Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: APV Dose in mg/kg units divided by AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.
- Plasma APV CL/F Following Dosing Expressed in mg [Week 48]
Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV).
- Plasma APV Tmax [Week 48]
The time to reach the maximum concentration (Cmax) at steady state is defined as tmax.
- Plasma APV t1/2 [Week 48]
The apparent terminal phase half-life (t1/2) is calculated as loge2/λz. The apparent terminal phase rate constant (λz) is the slope of the terminal portion of the logarithmically transformed concentration-time data as estimated by linear regression.
- Number of Participants Who Permanently Discontinued the Treatment Due to Any Adverse Event (AE) [Week 48]
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
- Change From Baseline in Triglycerides, Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Serum Glucose at Week 48 [Baseline (Day 1) and Week 48]
Blood samples of all participants were collected under fasting conditions for the evaluation of triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, and serum glucose. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, and serum glucose was calculated as the value at Week 48 minus the value at Baseline.
- Change From Baseline in Serum Lipase at Week 48 [Baseline (Day 1) and Week 48]
Blood samples of all participants were collected for the evaluation of serum lipase. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in serum lipase was calculated as the value at Week 48 minus the value at Baseline.
- Change From Baseline in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at Week 48 [Baseline (Day 1) and Week 48]
Blood samples of the participants were collected for the evaluation of AST and ALT. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in AST and ALT was calculated as the value at Week 48 minus the value at Baseline.
- Number of Participants With Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Laboratory Abnormalities [Baseline (Day 1) until Week 48]
A toxicity was considered TE if it was > than the Baseline grade, and if it was observed on/after the date of the first dose of study drug (SD), and on/before the date of the last dose of SD. Leucopenia is the decrease in the number of leucocytes (white blood cells [WBCs]); neutropenia is the decrease in the number of neutrophils (type of WBCs). Per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs: Grade 3 is "severe"; Grade 4 is "potentially life-threatening." ULN, upper limit of normal; LDL, low-density lipoprotein; PC, platelet count.
Secondary Outcome Measures
- Plasma Ritonavir (RTV) AUC (0-τ) [Week 48]
Plasma samples were assayed for RTV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma RTV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method.
- Plasma RTV Cmax [Week 48]
The maximum concentration at steady state (Cmax) was measured.
- Plasma RTV Cτ [Week 48]
The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured.
- Plasma RTV CL/F Following Dosing Expressed in mg/kg [Week 48]
Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: RTV Dose in mg/kg units divided by AUC(0-τ). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.
- Plasma RTV CL/F Following Dosing Expressed in mg [Week 48]
Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ).
- Plasma RTV Tmax [Week 48]
The time to reach the maximum concentration (Cmax) at steady state is defined as (tmax).
- Plasma RTV t1/2 [Week 48]
alf-life (t1/2) is calculated as loge2/λz. The apparent terminal phase rate constant (λz) is the slope of the terminal portion of the logarithmically transformed concentration-time data as estimated by linear regression.
- Plasma FPV AUC (0-τ) [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Plasma FPV Cmax and Cτ [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Plasma FPV CL/F Following Dosing Expressed in mg/kg [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Plasma FPV CL/F Following Dosing Expressed in mg [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Plasma FPV Tmax [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Plasma FPV t1/2 [Week 48]
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
- Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48 [Week 48]
Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced.Virologic success was defined as plasma HIV-1 RNA <400 copies/mL. Virologic failure: (1) HIV-1 RNA >=400 copies/mL, (2) change of background antiretroviral treatment (ART), (3) discontinued study due to lack of efficacy, (4) discontinued study with last HIV-1 >=400 copies/mL. No virologic data at Week 48 window: (a) discontinued study due to an adverse event or death, (b) discontinued study due to other reasons, (c) missing data during window but still on study.
- Number of Participants (Par.) With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 2,12, 24, and 48 (MSD=F) [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the Missing, Switch, or Discontinuation = Failure (MSD=F) analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders.
- Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis) [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA.
- Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis) [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA. Change from Baseline at Weeks 2, 12, 24, and 48 was calculated as value at Week 2, 12, 24, and 48 minus the value at Baseline.
- Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 2, 12, 24, and 48 (Observed Analysis) [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA.
- Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 2, 12, 24, and 48 [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected for the measurement of CD4+ cell count. Observed analysis was used for the summary of proportion endpoints using viral load data. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV.
- Change From Baseline in CD4+ Cell Count at Weeks 2, 12, 24, and 48 [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected for the measurement of CD4+ cell count. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline was calculated as the value at Weeks 2, 12, 24, and 48 minus the value at Baseline.
- Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Baseline and Weeks 2, 12, 24, and 48 [Baseline and Weeks 2, 12, 24, and 48]
Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data.
- Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Weeks 2, 12, 24, and 48 [Baseline and Week 2, 12, 24, 48]
Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline in percentage was calculated as the value at Weeks 2, 12, 24, and 48 minus the value at Baseline.
- Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease [Week 48]
A blood sample was drawn for par. failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience.
- Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease [After Week 48 through Week 240]
A blood sample was drawn for par. remaining in the study after Week 48 and failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience.
- Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS) [Baseline through 48 Weeks]
A blood sample was drawn for par. failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure.
- Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS) [Week 60 through Week 240]
A blood sample was drawn for par. remaining in the study after Week 48 and failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure.
- Number of Participants Reporting Perfect Adherence Over the 3 Days Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by Study Coordinator Using the Pediatric AIDS Clinical Trials Group (PACTG) Adherence Questionnaire [Weeks 2, 12, 24, and 48]
The PACTG Adherence Questionnaire records individual study drugs, the expected number of doses/24 hour period, and the number of doses missed in the 3 days prior to the study visit. Responses were summarized by age cohort, study drug, treatment regimen, and visit for exploratory analysis only.
- Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events [Week 48]
No formal analysis has been performed or is planned to correlate plasma APV PK with efficacy and safety outcomes.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Males or females 2 to 18 years of age Cohorts 1A and 1B, up to one month before 6th birthday at Baseline/Day 1 Cohort 2, up to one month before 12th birthday at Baseline/Day 1 Cohort 3, up to one month before 19th birthday at Baseline/Day 1
-
A female is eligible to enter and participate in this study if she is of:
-
non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
-
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). Premenarchial females who develop child-bearing potential while on the study will be expected to follow one of the methods of contraception listed below.
Agreement for 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 counseled and be willing to use one of the contraception 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.
Hormonal contraception is not recommended, due to decreased efficacy of contraception as well as increased risk of hepatic transaminase elevation (see Section 8.2).
All subjects of childbearing potential or developing child-bearing potential while participating in this study should be counseled 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 >=400copies/mL.
-
Subjects must meet one of the following criterion:
Antiretroviral therapy (ART)-naïve or PI-naïve subjects (defined as having received less than one week of any PI and any length of therapy with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and/or Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)).
PI-experienced subjects (defined as having received greater than one week prior PI therapy with no more than three PIs). Prior RTV boosted PI therapy will be considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral age
Exclusion criteria:
-
Prior history of having received APV or FPV for >7 days.
-
NNRTI use within 14 days prior to study drug administration or anticipated need for concurrent NNRTI therapy during the treatment period of the study.
-
Subjects who, in the investigator's opinion, are not able to comply with the requirements of the study.
-
Subject is in the initial acute phase of a Centers for Disease Control and Prevention (CDC) Clinical Category C event or infection (per 1994 classification) at Baseline. Subject may be enrolled provided they are receiving treatment for the infection, such treatment not being contraindicated with FPV, and the subjects are clinically improving at the Baseline visit.
-
Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the subject unable to take oral medication.
-
Pregnant or lactating females.
-
Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia, a history of insulin resistance, diabetes, cardiac dysfunction, hepatitis or clinically relevant pancreatitis) which, in the opinion of the investigator, might compromise the safety of the subject.
-
Grade 3 or 4 transaminase levels (ALT and/or AST) within 28 days prior to study drug administration and/or clinically relevant episodes of hepatitis within the previous 6 months.
-
Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the screening window. Any verified Grade 4 laboratory abnormality at screen would exclude a subject from study participation.
-
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:
Drugs whose plasma concentration may be increased to unsafe levels when co-administered with FPV including:
Amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, halofantrine, lidocaine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, quinidine, simvastatin, terfenadine, and triazolam
Drugs with the potential to significantly decrease plasma APV concentrations including:
Carbamazepine, dexamethasone, phenobarbital, primidone, rifampin, St Johns Wort.
-
Treatment with other investigational drugs/therapies (note: treatments available through a Treatment Investigational New Drug [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 or during the treatment period of the study.
-
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).
-
Substantial non-adherence based on history
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 | 90033 |
| 3 | GSK Investigational Site | Oakland | California | United States | 94609 |
| 4 | GSK Investigational Site | Jacksonville | Florida | United States | 32209 |
| 5 | GSK Investigational Site | Tampa | Florida | United States | 33606 |
| 6 | GSK Investigational Site | Boston | Massachusetts | United States | 02115-5724 |
| 7 | GSK Investigational Site | Boston | Massachusetts | United States | 02118 |
| 8 | GSK Investigational Site | Bronx | New York | United States | 10457 |
| 9 | GSK Investigational Site | New Hyde Park | New York | United States | 11042 |
| 10 | GSK Investigational Site | New York | New York | United States | 10016 |
| 11 | GSK Investigational Site | New York | New York | United States | 10021 |
| 12 | GSK Investigational Site | New York | New York | United States | 10037 |
| 13 | GSK Investigational Site | Durham | North Carolina | United States | 27710 |
| 14 | GSK Investigational Site | Philadelphia | Pennsylvania | United States | 19134 |
| 15 | GSK Investigational Site | Dallas | Texas | United States | 75235 |
| 16 | GSK Investigational Site | Fort Worth | Texas | United States | 76104 |
| 17 | GSK Investigational Site | Antwerpen | Belgium | 2020 | |
| 18 | GSK Investigational Site | Vancouver | British Columbia | Canada | V6H 3N1 |
| 19 | GSK Investigational Site | Winnipeg | Manitoba | Canada | R3E 3P4 |
| 20 | GSK Investigational Site | Toronto | Ontario | Canada | M5G 1X8 |
| 21 | GSK Investigational Site | Montreal | Quebec | Canada | H3T 1C5 |
| 22 | GSK Investigational Site | Bucharest | Romania | 021105 | |
| 23 | GSK Investigational Site | Bucharest | Romania | 030303 | |
| 24 | GSK Investigational Site | Moscow | Russian Federation | 105275 | |
| 25 | GSK Investigational Site | Moscow | Russian Federation | 129110 | |
| 26 | GSK Investigational Site | St. Petersburg | Russian Federation | 196645 | |
| 27 | GSK Investigational Site | Coronationville | Gauteng | South Africa | 2112 |
| 28 | GSK Investigational Site | Durban | KwaZulu- Natal | South Africa | 4013 |
| 29 | GSK Investigational Site | Parow Valley | Western Province | South Africa | 7505 |
| 30 | GSK Investigational Site | Soweto | South Africa | 2013 | |
| 31 | GSK Investigational Site | Barcelona | Spain | 08003 | |
| 32 | GSK Investigational Site | Barcelona | Spain | 08950 | |
| 33 | GSK Investigational Site | Madrid | Spain | 28041 | |
| 34 | GSK Investigational Site | Madrid | Spain | 28046 | |
| 35 | GSK Investigational Site | Malaga | Spain | 29010 | |
| 36 | GSK Investigational Site | Palma de Mallorca | Spain | 07014 | |
| 37 | GSK Investigational Site | Sevilla | Spain | 41013 | |
| 38 | GSK Investigational Site | Valencia | Spain | 46009 | |
| 39 | GSK Investigational Site | Vigo ( Pontevedra) | Spain | 36204 |
Sponsors and Collaborators
- ViiV Healthcare
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, ViiV Healthcare
Study Documents (Full-Text)
None provided.More Information
Publications
- Ross L, Cotton M, Cassim H, et al. HIV-1 drug resistance and mutational profile in fosamprenavir-treated HIV-infected children aged 2 months to 18 years at start of therapy. Presented at: AIDS 2012 - 19th International AIDS Conference; July 22-27, 2012; Washington DC.
- Voronin E, Fortuny C, Perez-Tamarit D, et al. Pharmacokinetics, safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2 to 18 year-old children (48-week data, Study APV29005, a prospective, open-label, multi-centre, 48-week cohort study). Presented at: AIDS 2012 - 19th International AIDS Conference; July 22-27, 2012; Washington, DC.
Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00089583
Other Study ID Numbers:
- APV29005
First Posted:
Aug 10, 2004
Last Update Posted:
Mar 7, 2017
Last Verified:
Jan 1, 2017
Keywords provided by ViiV Healthcare
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 110 participants (par.) were enrolled in the study; however, 1 par. withdrew from the study prior to the first dose of study drug and was not included in the Intent-to-Treat Exposed or Safety Populations. Therefore, 109 par. received >=1 dose of study drug and are thus categorized as starting the study in the Participant Flow module. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Period Title: Overall Study | ||
| STARTED | 20 | 89 |
| COMPLETED | 13 | 51 |
| NOT COMPLETED | 7 | 38 |
Baseline Characteristics
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group | Total |
|---|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. | Total of all reporting groups |
| Overall Participants | 20 | 89 | 109 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
2.9
(1.07)
|
10.0
(4.49)
|
8.7
(4.93)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
15
75%
|
43
48.3%
|
58
53.2%
|
| Male |
5
25%
|
46
51.7%
|
51
46.8%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Arabic/North African |
0
0%
|
1
1.1%
|
1
0.9%
|
| Black |
0
0%
|
43
48.3%
|
43
39.4%
|
| South Asian |
0
0%
|
1
1.1%
|
1
0.9%
|
| White/Caucasian |
19
95%
|
41
46.1%
|
60
55%
|
| Race Not Specified |
1
5%
|
3
3.4%
|
4
3.7%
|
| Par with the Indicated 1993 Center for Disease Control and Prevention (CDC) Baseline Classification (participants) [Number] | |||
| <13 years (yrs); mildly symptomatic (S) |
18
90%
|
26
29.2%
|
44
40.4%
|
| <13 yrs; moderately S |
1
5%
|
15
16.9%
|
16
14.7%
|
| <13 yrs; severely S |
0
0%
|
10
11.2%
|
10
9.2%
|
| <13 yrs; non-S |
1
5%
|
5
5.6%
|
6
5.5%
|
| >=13 yrs; asymptomatic/lymphadenopathy/acute HIV |
0
0%
|
12
13.5%
|
12
11%
|
| >=13 yrs; asymptomatic, not AIDS |
0
0%
|
14
15.7%
|
14
12.8%
|
| >=13 yrs; AIDS |
0
0%
|
5
5.6%
|
5
4.6%
|
| >=13 yrs; not reported |
0
0%
|
2
2.2%
|
2
1.8%
|
Outcome Measures
| Title | Plasma Amprenavir (APV) AUC (0-tau[τ]) |
|---|---|
| Description | Plasma samples were assayed for APV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma APV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method. hr, hour; µg, micrograms; mL, milliliter. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) Population: all participants for whom serial plasma PK samples were analyzed. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6 yrs, 30 mg/kg BID; n=9, 0 |
22.3
|
NA
|
| 2 to <6 yrs, 40 mg/kg BID; n=7, 0 |
24.1
|
NA
|
| 2 to <6 yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
55.3
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 9 |
NA
|
32.3
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 12 |
NA
|
48.4
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 3 |
NA
|
37.6
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
21.8
|
| 12 to 18 yrs, 18/3 mg BID; n=0, 3 |
NA
|
41.7
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 13 |
NA
|
35.3
|
| Title | Plasma APV Cmax |
|---|---|
| Description | The maximum concentration at steady state (Cmax) was measured. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6 yrs, 30 mg/kg BID; n=9, 0 |
7.15
|
NA
|
| 2 to <6 yrs, 40 mg/kg BID; n=7, 0 |
6.52
|
NA
|
| 2 to <6 yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
8.66
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 10 |
NA
|
4.34
|
| 6 to <12.yrs, 18/3 mg/kg BID; n=0, 12 |
NA
|
6.40
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 3 |
NA
|
5.85
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
3.92
|
| 12 to 18 yrs, 18/3 mg/kg BID; n=0, 4 |
NA
|
4.91
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 13 |
NA
|
4.93
|
| Title | Plasma APV Cτ |
|---|---|
| Description | The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 40 |
| 2 to <6 yrs, 30 mg/kg BID; n=19, 0 |
0.55
|
NA
|
| 2 to <6 yrs, 40 mg/kg BID; n=10, 0 |
0.70
|
NA
|
| 2 to <6 yrs, 23/3 mg/kg BID; n=0, 16 |
NA
|
3.39
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 13 |
NA
|
2.24
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 23 |
NA
|
2.42
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 7 |
NA
|
1.81
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 6 |
NA
|
1.45
|
| 12 to 18 yrs, 18/3 mg/kg BID; n=0, 10 |
NA
|
1.80
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 40 |
NA
|
2.01
|
| Title | Plasma APV CL/F Following Dosing Expressed in mg/kg |
|---|---|
| Description | Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: APV Dose in mg/kg units divided by AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6yrs, 30 mg/kg BID; n=9, 0 |
19.3
|
NA
|
| 2 to <6yrs, 40 mg/kg BID; n=7, 0 |
23.4
|
NA
|
| 2 to <6yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
6.06
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 9 |
NA
|
6.48
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 12 |
NA
|
5.27
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 3 |
NA
|
5.94
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
10.1
|
| 12 to 18 yrs, 18/3 mg BID; n=0, 3 |
NA
|
6.00
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 13 |
NA
|
5.33
|
| Title | Plasma APV CL/F Following Dosing Expressed in mg |
|---|---|
| Description | Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6yrs, 30 mg/kg BID; n=9, 0 |
269
|
NA
|
| 2 to <6yrs, 40 mg/kg BID; n=7, 0 |
330
|
NA
|
| 2 to <6yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
91
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 9 |
NA
|
195
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 12 |
NA
|
149
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 3 |
NA
|
266
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
392
|
| 12 to 18 yrs, 18/3 mg BID; n=0, 3 |
NA
|
198
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 13 |
NA
|
284
|
| Title | Plasma APV Tmax |
|---|---|
| Description | The time to reach the maximum concentration (Cmax) at steady state is defined as tmax. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6yrs, 30 mg/kg BID; n=9, 0 |
1.17
|
NA
|
| 2 to <6yrs, 40 mg/kg BID; n=7, 0 |
1.00
|
NA
|
| 2 to <6yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
1.25
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 10 |
NA
|
2.00
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 12 |
NA
|
1.96
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 3 |
NA
|
3.92
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
1.00
|
| 12 to 18 yrs, 18/3 mg BID; n=0, 3 |
NA
|
1.50
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 13 |
NA
|
2.00
|
| Title | Plasma APV t1/2 |
|---|---|
| Description | The apparent terminal phase half-life (t1/2) is calculated as loge2/λz. The apparent terminal phase rate constant (λz) is the slope of the terminal portion of the logarithmically transformed concentration-time data as estimated by linear regression. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 9 | 14 |
| 2 to <6yrs, 30 mg/kg BID; n=9, 0 |
3.03
|
NA
|
| 2 to <6yrs, 40 mg/kg BID; n=5, 0 |
3.18
|
NA
|
| 2 to <6yrs, 23/3 mg/kg BID; n=0, 14 |
NA
|
5.21
|
| 6 to <12 yrs, 15/3 mg/kg BID; n=0, 7 |
NA
|
10.5
|
| 6 to <12 yrs, 18/3 mg/kg BID; n=0, 10 |
NA
|
8.41
|
| 6 to <12 yrs, 700/100 mg BID; n=0, 2 |
NA
|
7.43
|
| 12 to 18 yrs, 15/3 mg/kg BID; n=0, 4 |
NA
|
6.12
|
| 12 to 18 yrs, 18/3 mg BID; n=0, 4 |
NA
|
8.76
|
| 12 to 18 yrs, 700/100 mg BID; n=0, 11 |
NA
|
7.64
|
| Title | Number of Participants Who Permanently Discontinued the Treatment Due to Any Adverse Event (AE) |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants with documented evidence of having received at least one dose of investigational treatment. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 20 | 89 |
| Number [participants] |
0
0%
|
4
4.5%
|
| Title | Change From Baseline in Triglycerides, Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Serum Glucose at Week 48 |
|---|---|
| Description | Blood samples of all participants were collected under fasting conditions for the evaluation of triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, and serum glucose. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, and serum glucose was calculated as the value at Week 48 minus the value at Baseline. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 18 | 69 |
| Triglycerides; n=17, 65 |
0.1
|
0.2
|
| Total cholesterol; n=17, 65 |
1.1
|
0.9
|
| HDL cholesterol; n=17, 65 |
0.4
|
0.3
|
| LDL cholesterol; n=17, 64 |
0.6
|
0.5
|
| Glucose; n=18, 69 |
0.0
|
0.1
|
| Title | Change From Baseline in Serum Lipase at Week 48 |
|---|---|
| Description | Blood samples of all participants were collected for the evaluation of serum lipase. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in serum lipase was calculated as the value at Week 48 minus the value at Baseline. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 18 | 69 |
| Median (Inter-Quartile Range) [Units per liter (U/L)] |
-2.0
|
-1.0
|
| Title | Change From Baseline in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at Week 48 |
|---|---|
| Description | Blood samples of the participants were collected for the evaluation of AST and ALT. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in AST and ALT was calculated as the value at Week 48 minus the value at Baseline. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 18 | 70 |
| ALT |
-3
|
-7
|
| AST |
-6
|
-9
|
| Title | Number of Participants With Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Laboratory Abnormalities |
|---|---|
| Description | A toxicity was considered TE if it was > than the Baseline grade, and if it was observed on/after the date of the first dose of study drug (SD), and on/before the date of the last dose of SD. Leucopenia is the decrease in the number of leucocytes (white blood cells [WBCs]); neutropenia is the decrease in the number of neutrophils (type of WBCs). Per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs: Grade 3 is "severe"; Grade 4 is "potentially life-threatening." ULN, upper limit of normal; LDL, low-density lipoprotein; PC, platelet count. |
| Time Frame | Baseline (Day 1) until Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 20 | 87 |
| ALT increased (inc.) (>5.0x ULN); n=20, 87 |
2
10%
|
2
2.2%
|
| AST inc. (>5.0x ULN); n=20, 87 |
2
10%
|
2
2.2%
|
| Cholesterol (Chol.) inc. (>7.77 mmol/L); n=16, 43 |
0
0%
|
2
2.2%
|
| Hyperglycemia (>13.88 mmol/L); n=16, 58 |
0
0%
|
0
0%
|
| Hypoglycemia (<2.22 mmol/L); n=16, 58 |
0
0%
|
0
0%
|
| LDL Chol. inc. (>=4.91 mmol/L); n=16, 43 |
0
0%
|
4
4.5%
|
| Triglycerides inc. (>8.48 mmol/L); n=16, 43 |
0
0%
|
0
0%
|
| Lipase inc. (>3.0x ULN); n=19, 85 |
0
0%
|
0
0%
|
| Leucopenia (<1.500 x 10^9/L); n=20, 84 |
0
0%
|
0
0%
|
| Neutropenia (<0.750 x 10^9/L); n=20, 84 |
8
40%
|
7
7.9%
|
| Hemoglobin > anemia (<1.16 mmol/L); n=20, 85 |
0
0%
|
0
0%
|
| PC > thrombocytopenia (<50.000 x 10^9/L); n=20, 85 |
0
0%
|
1
1.1%
|
| Title | Plasma Ritonavir (RTV) AUC (0-τ) |
|---|---|
| Description | Plasma samples were assayed for RTV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma RTV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: all participants for whom a plasma PK sample was analyzed. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 15 |
| 2 to <6 yrs, 3 mg/kg BID; n=0, 10 |
3.98
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 12 |
7.13
|
|
| 6 to <12 yrs, 100 mg BID; n=0, 6 |
6.46
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 1 |
5.74
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 15 |
6.13
|
| Title | Plasma RTV Cmax |
|---|---|
| Description | The maximum concentration at steady state (Cmax) was measured. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 16 |
| 2 to <6 yrs, 3 mg/kg BID; n=0, 10 |
0.633
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 14 |
1.100
|
|
| 6 to <12.yrs, 100 mg BID; n=0, 6 |
0.980
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 3 |
0.750
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 16 |
1.06
|
| Title | Plasma RTV Cτ |
|---|---|
| Description | The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 41 |
| 2 to <6 yrs, 3 mg/kg BID; n=0, 16 |
0.224
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 24 |
0.297
|
|
| 6 to <12 yrs, 100 mg BID; n=0, 10 |
0.228
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 6 |
0.263
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 41 |
0.220
|
| Title | Plasma RTV CL/F Following Dosing Expressed in mg/kg |
|---|---|
| Description | Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: RTV Dose in mg/kg units divided by AUC(0-τ). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 15 |
| 2 to <6yrs, 3 mg/kg BID; n=0, 10 |
12.9
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 12 |
6.81
|
|
| 6 to <12 yrs, 100 mg/kg BID; n=0, 12 |
5.94
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 1 |
8.61
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 15 |
5.59
|
| Title | Plasma RTV CL/F Following Dosing Expressed in mg |
|---|---|
| Description | Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ). |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 15 |
| 2 to <6yrs, 3 mg/kg BID; n=0, 10 |
195
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 12 |
190
|
|
| 6 to <12 yrs, 100 mg/kg BID; n=0, 6 |
258
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 1 |
279
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 15 |
272
|
| Title | Plasma RTV Tmax |
|---|---|
| Description | The time to reach the maximum concentration (Cmax) at steady state is defined as (tmax). |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: all participants for whom a plasma PK sample was analyzed. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 15 |
| 2 to <6 yrs, 3 mg/kg BID; n=0, 10 |
3.92
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 14 |
4.00
|
|
| 6 to <12 yrs, 100 mg BID; n=0, 6 |
4.01
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 3 |
5.92
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 16 |
3.96
|
| Title | Plasma RTV t1/2 |
|---|---|
| Description | alf-life (t1/2) is calculated as loge2/λz. The apparent terminal phase rate constant (λz) is the slope of the terminal portion of the logarithmically transformed concentration-time data as estimated by linear regression. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants in the FPV arm did not take RTV; hence, they were not analyzed for this outcome measure. In the FPV/RTV arm, only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 14 |
| 2 to <6 yrs, 3 mg/kg BID; n=0, 10 |
3.43
|
|
| 6 to <12 yrs, 3 mg/kg BID; n=0, 11 |
3.39
|
|
| 6 to <12 yrs, 100 mg BID; n=0, 5 |
3.97
|
|
| 12 to 18 yrs, 3 mg/kg BID; n=0, 1 |
2.84
|
|
| 12 to 18 yrs, 100 mg BID; n=0, 14 |
3.64
|
| Title | Plasma FPV AUC (0-τ) |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Plasma FPV Cmax and Cτ |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Plasma FPV CL/F Following Dosing Expressed in mg/kg |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Plasma FPV CL/F Following Dosing Expressed in mg |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Plasma FPV Tmax |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Plasma FPV t1/2 |
|---|---|
| Description | The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
| Title | Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48 |
|---|---|
| Description | Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced.Virologic success was defined as plasma HIV-1 RNA <400 copies/mL. Virologic failure: (1) HIV-1 RNA >=400 copies/mL, (2) change of background antiretroviral treatment (ART), (3) discontinued study due to lack of efficacy, (4) discontinued study with last HIV-1 >=400 copies/mL. No virologic data at Week 48 window: (a) discontinued study due to an adverse event or death, (b) discontinued study due to other reasons, (c) missing data during window but still on study. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed (ITT-E) Population: par. with documented evidence of receiving >=1 treatment dose. Only par. contributing data were analyzed. The number of par. analyzed is the sum of the PI-naïve (received <1week's treatment with a PI) and -experienced (received >1week prior PI therapy with no more than 3 PIs before trial enrollment) par. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 20 | 89 |
| PI-naïve, virological (V) success; n=20, 49 |
12
60%
|
36
40.4%
|
| PI-exp, V success; n=0, 40 |
NA
NaN
|
19
21.3%
|
| PI-naïve, V failure (1); n=20, 49 |
4
20%
|
3
3.4%
|
| PI-exp, V failure (1); n=0, 40 |
NA
NaN
|
8
9%
|
| PI-naïve, V failure (2); n=20, 49 |
2
10%
|
4
4.5%
|
| PI-exp, V failure (2); n=0, 40 |
NA
NaN
|
7
7.9%
|
| PI-naïve, V failure (3); n=20, 49 |
1
5%
|
0
0%
|
| PI-exp, V failure (3); n=0, 40 |
NA
NaN
|
0
0%
|
| PI-naïve;, V failure (4); n=20, 49 |
1
5%
|
3
3.4%
|
| PI-exp, V failure (4); n=0, 40 |
NA
NaN
|
3
3.4%
|
| PI-naïve, No V data at Week 48 (a); n=20, 49 |
0
0%
|
1
1.1%
|
| PI-exp, No V data at Week 48 (a); n=0, 40 |
NA
NaN
|
1
1.1%
|
| PI-naïve, No V data Week 48 (b); n=20, 49 |
0
0%
|
1
1.1%
|
| PI-exp, No V data at Week 48 (b); n=0, 40 |
NA
NaN
|
0
0%
|
| PI-naïve, No V data at Week 48 (c); n=20, 49 |
0
0%
|
1
1.1%
|
| PI-exp, No V data at Week 48 (c); n=0, 40 |
NA
NaN
|
2
2.2%
|
| Title | Number of Participants (Par.) With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 2,12, 24, and 48 (MSD=F) |
|---|---|
| Description | Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the Missing, Switch, or Discontinuation = Failure (MSD=F) analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed (ITT-E) Population. Only those par. contributing data at the indicated time points were analyzed. The number of par. analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1week prior PI therapy with no more than 3 PIs before trial enrollment) par. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 20 | 89 |
| PI-naïve, Baseline; n=20, 49 |
0
0%
|
0
0%
|
| PI-exp, Baseline; n=0, 40 |
NA
NaN
|
0
0%
|
| PI-naïve, Week 2; n=20, 49 |
3
15%
|
9
10.1%
|
| PI-exp, Week 2; n=0, 40 |
NA
NaN
|
5
5.6%
|
| PI-naïve, Week 12; n=20, 49 |
13
65%
|
35
39.3%
|
| PI-exp, Week 12; n=0, 40 |
NA
NaN
|
19
21.3%
|
| PI-naïve, Week 24; n=20, 49 |
13
65%
|
35
39.3%
|
| PI-exp, Week 24; n=0, 40 |
NA
NaN
|
22
24.7%
|
| PI-naïve, Week 48; n=20, 49 |
12
60%
|
36
40.4%
|
| PI-exp, Week 48; n=0, 40 |
NA
NaN
|
19
21.3%
|
| Title | Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis) |
|---|---|
| Description | Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. In the observed analysis, data are presented for the number of par. still enrolled in the study at a certain time point. The number of par. analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) par. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 20 | 88 |
| PI-naïve, Baseline; n=20, 49 |
5.13
|
4.72
|
| PI-exp, Baseline; n=0, 39 |
NA
|
4.53
|
| PI-naïve, Week 2; n=14, 39 |
3.27
|
3.06
|
| PI-exp, Week 2; n=0, 33 |
NA
|
3.04
|
| PI-naïve, Week 12; n=19, 46 |
2.03
|
1.94
|
| PI-exp, Week 12; n=0, 34 |
NA
|
2.20
|
| PI-naïve, Week 24; n=18, 44 |
1.85
|
1.69
|
| PI-exp, Week 24; n=0, 35 |
NA
|
1.80
|
| PI-naïve, Week 48; n=18, 44 |
1.85
|
1.69
|
| PI-exp, Week 48; n=0, 33 |
NA
|
1.69
|
| Title | Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis) |
|---|---|
| Description | Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA. Change from Baseline at Weeks 2, 12, 24, and 48 was calculated as value at Week 2, 12, 24, and 48 minus the value at Baseline. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. In the observed analysis, data are presented for the number of par. still enrolled in the study at a certain time point. The number of par. analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) par. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 79 |
| PI-naïve, Week 2; n=14, 39 |
-1.91
|
-1.84
|
| PI-exp, Week 2; n=0, 32 |
NA
|
-1.58
|
| PI-naïve, Week 12; n=19, 46 |
-3.04
|
-2.77
|
| PI-exp, Week 12; n=0, 33 |
NA
|
-2.23
|
| PI-naïve, Week 24; n=18, 44 |
-3.16
|
-2.87
|
| PI-exp, Week 24; n=0, 35 |
NA
|
-2.28
|
| PI-naïve, Week 48; n=18, 44 |
-3.02
|
-2.83
|
| PI-exp, Week 48; n=0, 33 |
NA
|
-2.14
|
| Title | Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 2, 12, 24, and 48 (Observed Analysis) |
|---|---|
| Description | Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. In the observed analysis, data are presented for the number of par. still enrolled in the study at a certain time point. The number of par. analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) par. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 79 |
| PI-naïve, Week 2; n=14, 39 |
13
65%
|
35
39.3%
|
| PI-exp, Week 2; n=0, 32 |
NA
NaN
|
22
24.7%
|
| PI-naïve, Week 12; n=19, 46 |
19
95%
|
41
46.1%
|
| PI-exp, Week 12; n=0, 33 |
NA
NaN
|
26
29.2%
|
| PI-naïve, Week 24; n=18, 44 |
18
90%
|
41
46.1%
|
| PI-exp, Week 24; n=0, 35 |
NA
NaN
|
29
32.6%
|
| PI-naïve, Week 48; n=18, 44 |
17
85%
|
40
44.9%
|
| PI-exp, Week 48; n=0, 33 |
NA
NaN
|
24
27%
|
| Title | Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 2, 12, 24, and 48 |
|---|---|
| Description | Blood samples of participants were collected for the measurement of CD4+ cell count. Observed analysis was used for the summary of proportion endpoints using viral load data. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. Only those participants contributing data at the indicated time points were analyzed. The number of participants analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) participants. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 89 |
| PI-naïve, Baseline; n= 19, 49 |
810
(387.42)
|
370
(399.39)
|
| PI-naïve, Week 2; n= 13, 41 |
820
(370.81)
|
450
(575.73)
|
| PI-naïve, Week 12; n= 19, 46 |
1040
(606.25)
|
581
(555.52)
|
| PI-naïve, Week 24; n= 18, 44 |
1260
(482.92)
|
609
(509.24)
|
| PI-naïve, Week 48; n= 18, 42 |
1080
(611.28)
|
670
(568.20)
|
| PI-exp, Baseline; n= 0, 40 |
NA
(0)
|
440
(562.00)
|
| PI-exp, Week 2; n= 0, 32 |
NA
(0)
|
605
(444.63)
|
| PI-exp, Week 12; n= 0, 31 |
NA
(0)
|
720
(379.84)
|
| PI-exp, Week 24; n= 0, 34 |
NA
(0)
|
620
(420.62)
|
| PI-exp, Week 48; n= 0, 29 |
NA
(0)
|
540
(297.80)
|
| Title | Change From Baseline in CD4+ Cell Count at Weeks 2, 12, 24, and 48 |
|---|---|
| Description | Blood samples of participants were collected for the measurement of CD4+ cell count. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline was calculated as the value at Weeks 2, 12, 24, and 48 minus the value at Baseline. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. Only those participants contributing data at the indicated time points were analyzed. The number of participants analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) participants. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 78 |
| PI-naïve, Week 2; n=13, 41 |
20
|
60
|
| PI-naïve, Week 12; n=19, 46 |
170
|
180
|
| PI-naïve, Week 24; n=18, 44 |
350
|
184
|
| PI-naïve, Week 48; n=17, 42 |
340
|
217
|
| PI-exp, Week 2; n=0, 32 |
NA
|
90
|
| PI-exp, Week 12; n=0, 31 |
NA
|
200
|
| PI-exp, Week 24; n=0, 34 |
NA
|
150
|
| PI-exp, Week 48; n=0, 29 |
NA
|
180
|
| Title | Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Baseline and Weeks 2, 12, 24, and 48 |
|---|---|
| Description | Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. |
| Time Frame | Baseline and Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. Only those participants contributing data at the indicated time points were analyzed. The number of participants analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) participants. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 89 |
| PI-naïve, Baseline; n=19, 49 |
19
|
21
|
| PI-naïve, Week 2; n=13, 41 |
24
|
23
|
| PI-naïve, Week 12; n=19, 46 |
27
|
25
|
| PI-naïve, Week 24; n=18, 44 |
31
|
28
|
| PI-naïve, Week 48; n=18, 42 |
32
|
29
|
| PI-exp, Baseline; n=0, 40 |
NA
|
24
|
| PI-exp, Week 2; n=0, 32 |
NA
|
22
|
| PI-exp, Week 12; n=0, 31 |
NA
|
23
|
| PI-exp, Week 24; n=0, 34 |
NA
|
23
|
| PI-exp, Week 48; n=0, 29 |
NA
|
24
|
| Title | Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Weeks 2, 12, 24, and 48 |
|---|---|
| Description | Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline in percentage was calculated as the value at Weeks 2, 12, 24, and 48 minus the value at Baseline. |
| Time Frame | Baseline and Week 2, 12, 24, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-E Population. Only those participants contributing data at the indicated time points were analyzed. The number of participants analyzed represents the sum of the PI-naïve (received <1 week's treatment with a PI) and -experienced (received >1 week prior PI therapy with no more than 3 PIs before trial enrollment) participants. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 19 | 78 |
| PI-naïve, Week 2; n=13, 41 |
3
|
1
|
| PI-naïve, Week 12; n=19, 46 |
6
|
5
|
| PI-naïve, Week 24; n=18, 44 |
7
|
8
|
| PI-naïve, Week 48; n=17, 42 |
8
|
10
|
| PI-exp, Week 2; n=0, 32 |
NA
|
2
|
| PI-exp, Week 12; n=0, 31 |
NA
|
3
|
| PI-exp, Week 24; n=0, 34 |
NA
|
5
|
| PI-exp, Week 48; n=0, 29 |
NA
|
6
|
| Title | Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease |
|---|---|
| Description | A blood sample was drawn for par. failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral genotype at both baseline and the indicated time of VF points were evaluable. |
| Arm/Group Title | ART-Naïve, FPV Treatment Group | ART-Naïve, FPV/RTV Treatment Group | PI Naïve, ART Experienced, FPV/RTV Treatment Group | PI Experienced, ART Experienced, FPV/RTV Treatment Group |
|---|---|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral-naive pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID) | HIV-1-infected, antiretroviral-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, antiretroviral-experienced but PI-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, PI-experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID |
| Measure Participants | 3 | 1 | 3 | 8 |
| Any HIV NRTI Mutation |
3
15%
|
0
0%
|
0
0%
|
1
NaN
|
| HIV NRTI mutation M184V |
3
15%
|
0
0%
|
0
0%
|
1
NaN
|
| Any HIV NNRTI Mutation |
0
0%
|
0
0%
|
0
0%
|
1
NaN
|
| HIV NNRTI Mutation V179D/E |
0
0%
|
0
0%
|
0
0%
|
1
NaN
|
| Any HIV Major PI Mutations |
2
10%
|
0
0%
|
1
0.9%
|
1
NaN
|
| HIV Major PI Mutation M46M/I |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| HIV Major PI Mutation M46M/L |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| HIV Major PI Mutation I50I/V |
1
5%
|
0
0%
|
1
0.9%
|
1
NaN
|
| HIV Major PI Mutation I54I/L |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| HIV Major PI Mutation I54I/M |
0
0%
|
0
0%
|
0
0%
|
1
NaN
|
| HIV Major PI Mutation I54I/M/V |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| HIV Major PI Mutation Q58Q/E |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| HIV Major PI Mutation V82A/V |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| HIV Major PI Mutation V82F/I |
0
0%
|
0
0%
|
0
0%
|
1
NaN
|
| HIV Major PI Mutation I84I/V |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| Any Minor HIV PI Mutations |
2
10%
|
0
0%
|
1
0.9%
|
1
NaN
|
| Minor HIV PI Mutation L10L/F |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| Minor HIV PI Mutation K20K/R |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| Minor HIV PI Mutation L33L/F |
1
5%
|
0
0%
|
1
0.9%
|
0
NaN
|
| Minor HIV PI Mutation K43K/T |
0
0%
|
0
0%
|
0
0%
|
1
NaN
|
| Minor HIV PI Mutation F53F/L |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| Minor HIV PI Mutation F53L |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| Minor HIV PI Mutation I62I/V |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| Minor HIV PI Mutation A71I/V |
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
| Minor HIV PI Mutation I85I/V |
0
0%
|
0
0%
|
1
0.9%
|
1
NaN
|
| Title | Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease |
|---|---|
| Description | A blood sample was drawn for par. remaining in the study after Week 48 and failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience. |
| Time Frame | After Week 48 through Week 240 |
Outcome Measure Data
| Analysis Population Description |
|---|
| VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral genotype at both baseline and the indicated time of VF points were evaluable. |
| Arm/Group Title | ART-Naïve, FPV Treatment Group | ART-Naïve, FPV/RTV Treatment Group | PI Naïve, ART Experienced, FPV/RTV Treatment Group | PI Experienced, ART Experienced, FPV/RTV Treatment Group |
|---|---|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral-naive pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID) | HIV-1-infected, antiretroviral-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, antiretroviral-experienced but PI-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, PI-experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID |
| Measure Participants | 1 | 1 | 0 | 5 |
| Any HIV NRTI Mutation |
1
5%
|
1
1.1%
|
2
1.8%
|
|
| HIV NRTI mutation M41L |
0
0%
|
0
0%
|
1
0.9%
|
|
| HIV NRTI mutation M184I |
0
0%
|
1
1.1%
|
0
0%
|
|
| HIV NRTI mutation M184V |
1
5%
|
0
0%
|
2
1.8%
|
|
| HIV NRTI mutation T215S/Y |
0
0%
|
0
0%
|
1
0.9%
|
|
| Any Major HIV NNRTI Mutation |
0
0%
|
0
0%
|
1
0.9%
|
|
| HIV NNRTI Mutation K103N |
0
0%
|
0
0%
|
1
0.9%
|
|
| Any Minor HIV NNRTI Mutation |
0
0%
|
0
0%
|
0
0%
|
|
| HIV NNRTI Mutation V179D/E |
0
0%
|
0
0%
|
0
0%
|
|
| Any HIV Major PI Mutations |
1
5%
|
0
0%
|
1
0.9%
|
|
| HIV Major PI Mutation V32I |
0
0%
|
0
0%
|
1
0.9%
|
|
| HIV Major PI Mutation M46L |
1
5%
|
0
0%
|
0
0%
|
|
| HIV Major PI Mutation I47IV |
0
0%
|
0
0%
|
1
0.9%
|
|
| HIV Major PI Mutation T74P |
1
5%
|
0
0%
|
0
0%
|
|
| HIV Major PI Mutation I84I/V |
0
0%
|
0
0%
|
0
0%
|
|
| Any Minor HIV PI Mutations |
1
5%
|
0
0%
|
2
1.8%
|
|
| Minor HIV PI Mutation L10F |
1
5%
|
0
0%
|
0
0%
|
|
| Minor HIV PI Mutation L33F |
0
0%
|
0
0%
|
1
0.9%
|
|
| Minor HIV PI Mutation I62I/V |
0
0%
|
0
0%
|
1
0.9%
|
|
| Minor HIV PI Mutation I85V |
1
5%
|
0
0%
|
0
0%
|
| Title | Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS) |
|---|---|
| Description | A blood sample was drawn for par. failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure. |
| Time Frame | Baseline through 48 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral phenotype at both baseline and the indicated time of VF points were evaluable |
| Arm/Group Title | ART-Naïve, FPV Treatment Group | ART-Naïve, FPV/RTV Treatment Group | PI Naïve, ART-experienced, FPV/RTV Treatment Group | PI-experienced, ART-experienced FPV/RTV Treatment Group |
|---|---|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral-naive pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID) | HIV-1-infected, antiretroviral-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, antiretroviral-experienced but PI- pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, PI-experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID |
| Measure Participants | 3 | 1 | 3 | 8 |
| Any NRTI |
3
15%
|
0
0%
|
0
0%
|
2
NaN
|
| Abacavir |
1
5%
|
0
0%
|
0
0%
|
0
NaN
|
| Didanosine |
3
15%
|
0
0%
|
0
0%
|
1
NaN
|
| Emtricitabine |
3
15%
|
0
0%
|
0
0%
|
1
NaN
|
| Lamivudine |
3
15%
|
0
0%
|
0
0%
|
1
NaN
|
| Any NNRTI |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Any PI |
2
10%
|
0
0%
|
1
0.9%
|
1
NaN
|
| Unboosted Fosamprenavir |
2
10%
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Ritonavir- boosted Fosamprenavir |
NA
NaN
|
0
0%
|
1
0.9%
|
1
NaN
|
| Ritonavir |
2
10%
|
0
0%
|
0
0%
|
0
NaN
|
| Title | Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS) |
|---|---|
| Description | A blood sample was drawn for par. remaining in the study after Week 48 and failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure. |
| Time Frame | Week 60 through Week 240 |
Outcome Measure Data
| Analysis Population Description |
|---|
| VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral phenotype at both baseline and the indicated time of VF points were evaluable |
| Arm/Group Title | ART-Naïve, FPV Treatment Group | ART-Naïve, FPV/RTV Treatment Group | PI Naïve, ART-experienced, FPV/RTV Treatment Group | PI-experienced, ART-experienced FPV/RTV Treatment Group |
|---|---|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral-naive pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID) | HIV-1-infected, antiretroviral-naïve pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, antiretroviral-experienced but PI- pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID | HIV-1-infected, PI-experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID |
| Measure Participants | 1 | 1 | 0 | 5 |
| Any NRTI |
1
5%
|
1
1.1%
|
3
2.8%
|
|
| Abacavir |
0
0%
|
0
0%
|
1
0.9%
|
|
| Didanosine |
0
0%
|
1
1.1%
|
3
2.8%
|
|
| Emtricitabine |
1
5%
|
1
1.1%
|
3
2.8%
|
|
| Lamivudine |
1
5%
|
1
1.1%
|
2
1.8%
|
|
| Zidovudine |
0
0%
|
0
0%
|
1
0.9%
|
|
| Any NNRTI |
0
0%
|
0
0%
|
1
0.9%
|
|
| Delaviridine |
0
0%
|
0
0%
|
1
0.9%
|
|
| Efavirenz |
0
0%
|
0
0%
|
1
0.9%
|
|
| Nevirapine |
0
0%
|
0
0%
|
1
0.9%
|
|
| Any PI |
1
5%
|
1
1.1%
|
3
2.8%
|
|
| Unboosted Fosamprenavir |
1
5%
|
NA
NaN
|
NA
NaN
|
|
| Ritonavir- boosted Fosamprenavir |
NA
NaN
|
0
0%
|
1
0.9%
|
|
| Nelfinavir |
0
0%
|
1
1.1%
|
0
0%
|
|
| Tipranavir |
0
0%
|
0
0%
|
1
0.9%
|
| Title | Number of Participants Reporting Perfect Adherence Over the 3 Days Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by Study Coordinator Using the Pediatric AIDS Clinical Trials Group (PACTG) Adherence Questionnaire |
|---|---|
| Description | The PACTG Adherence Questionnaire records individual study drugs, the expected number of doses/24 hour period, and the number of doses missed in the 3 days prior to the study visit. Responses were summarized by age cohort, study drug, treatment regimen, and visit for exploratory analysis only. |
| Time Frame | Weeks 2, 12, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only those participants contributing data at the indicated time points were analyzed. |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 17 | 59 |
| Week 2, Total Population; n= 17, 59 |
15
75%
|
49
55.1%
|
| Week 2, 2 to <6 years (yrs); n= 17, 16 |
15
75%
|
15
16.9%
|
| Week 2, 6 to <12 yrs; n= 0, 25 |
NA
NaN
|
22
24.7%
|
| Week 2, 12 to 18 yrs; n= 0, 18 |
NA
NaN
|
12
13.5%
|
| Week 12, Total Population; n= 16, 55 |
15
75%
|
45
50.6%
|
| Week 12, 2 to <6 yrs; n= 16, 16 |
15
75%
|
14
15.7%
|
| Week 12, 6 to <12 yrs; n= 0, 24 |
NA
NaN
|
20
22.5%
|
| Week 12, 12 to 18 yrs; n= 0, 15 |
NA
NaN
|
11
12.4%
|
| Week 24, Total Population; n= 16, 54 |
16
80%
|
43
48.3%
|
| Week 24, 2 to <6 yrs; n= 16, 14 |
16
80%
|
11
12.4%
|
| Week 24, 6 to <12 yrs; n= 0, 24 |
NA
NaN
|
23
25.8%
|
| Week 24, 12 to 18 yrs; n= 0, 16 |
NA
NaN
|
9
10.1%
|
| Week 48, Total Population; n= 15, 53 |
13
65%
|
42
47.2%
|
| Week 48, 2 to <6 yrs; n= 15, 14 |
13
65%
|
13
14.6%
|
| Week 48, 6 to <12 yrs; n= 0, 23 |
NA
NaN
|
20
22.5%
|
| Week 48, 12 to 18 yrs; n= 0, 16 |
NA
NaN
|
9
10.1%
|
| Title | Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events |
|---|---|
| Description | No formal analysis has been performed or is planned to correlate plasma APV PK with efficacy and safety outcomes. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group |
|---|---|---|
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | FPV Treatment Group | FPV/RTV Treatment Group | ||
| Arm/Group Description | Human immunodeficiency virus type 1 (HIV-1)-infected, protease inhibitor (PI)-naïve pediatric participants, 2 to <6 years old, receiving fosamprenavir (FPV) oral suspension 30-40 milligrams per kilogram (mg/kg) twice a day (BID). PI-naïve participants are defined as those participants who received less than one week of any PI and any length of therapy with nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs). | HIV-1-infected, PI-naïve and -experienced pediatric participants, 2 to 18 years old, receiving FPV boosted with ritonavir (FPV/RTV) BID. Participants who were 2-<6 years old received FPV oral suspension/ritonavir oral solution 20/4 or 23/3 mg/kg BID; participants who were 6 years old or older received FPV oral suspension/RTV oral solution 15/3 or 18/3 mg/kg BID. A 700/100 mg BID tablet regimen was administered to participants able to take tablets/capsules. PI-experienced participants are defined as those participants who received more than one week of prior PI therapy with no more than three PIs. Prior RTV-boosted therapy was considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent. | ||
All Cause Mortality |
||||
| FPV Treatment Group | FPV/RTV Treatment Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| FPV Treatment Group | FPV/RTV Treatment Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/20 (25%) | 13/89 (14.6%) | ||
| Gastrointestinal disorders | ||||
| Dental caries | 0/20 (0%) | 1/89 (1.1%) | ||
| General disorders | ||||
| Adverse drug reaction | 0/20 (0%) | 1/89 (1.1%) | ||
| Pyrexia | 0/20 (0%) | 1/89 (1.1%) | ||
| Immune system disorders | ||||
| Drug hypersensitivity | 3/20 (15%) | 6/89 (6.7%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/20 (5%) | 2/89 (2.2%) | ||
| Respiratory tract infection | 1/20 (5%) | 1/89 (1.1%) | ||
| Cellulitis | 0/20 (0%) | 1/89 (1.1%) | ||
| Ear infection | 0/20 (0%) | 1/89 (1.1%) | ||
| Gastroenteritis | 1/20 (5%) | 0/89 (0%) | ||
| Hepatitis B | 0/20 (0%) | 1/89 (1.1%) | ||
| Measles | 0/20 (0%) | 1/89 (1.1%) | ||
| Pyelonephritis | 0/20 (0%) | 1/89 (1.1%) | ||
| Urinary tract infection | 0/20 (0%) | 1/89 (1.1%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 0/20 (0%) | 1/89 (1.1%) | ||
| Blood creatine phosphokinase increased | 0/20 (0%) | 1/89 (1.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Flank pain | 0/20 (0%) | 1/89 (1.1%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 0/20 (0%) | 1/89 (1.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| FPV Treatment Group | FPV/RTV Treatment Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/20 (90%) | 74/89 (83.1%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 0/20 (0%) | 7/89 (7.9%) | ||
| Eye disorders | ||||
| Conjunctivitis | 0/20 (0%) | 8/89 (9%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 12/20 (60%) | 28/89 (31.5%) | ||
| Diarrhea | 2/20 (10%) | 26/89 (29.2%) | ||
| Nausea | 1/20 (5%) | 10/89 (11.2%) | ||
| Abdominal pain | 0/20 (0%) | 7/89 (7.9%) | ||
| Dental caries | 0/20 (0%) | 6/89 (6.7%) | ||
| General disorders | ||||
| Pyrexia | 1/20 (5%) | 19/89 (21.3%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 3/20 (15%) | 20/89 (22.5%) | ||
| Nasopharyngitis | 1/20 (5%) | 16/89 (18%) | ||
| Respiratory tract infection | 12/20 (60%) | 4/89 (4.5%) | ||
| Rhinitis | 2/20 (10%) | 15/89 (16.9%) | ||
| Bronchitis | 3/20 (15%) | 12/89 (13.5%) | ||
| Ear infection | 3/20 (15%) | 11/89 (12.4%) | ||
| Otitis media | 0/20 (0%) | 11/89 (12.4%) | ||
| Pharyngitis | 1/20 (5%) | 8/89 (9%) | ||
| Gasrtroenteritis | 0/20 (0%) | 7/89 (7.9%) | ||
| Tonsillitis | 1/20 (5%) | 6/89 (6.7%) | ||
| Tinea capitis | 0/20 (0%) | 6/89 (6.7%) | ||
| Nervous system disorders | ||||
| Headache | 0/20 (0%) | 14/89 (15.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/20 (5%) | 33/89 (37.1%) | ||
| Rhinorrhoea | 1/20 (5%) | 10/89 (11.2%) | ||
| Oropharyngeal pain | 0/20 (0%) | 9/89 (10.1%) | ||
| Nasal congestion | 0/20 (0%) | 8/89 (9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 0/20 (0%) | 14/89 (15.7%) | ||
| Eczema | 1/20 (5%) | 5/89 (5.6%) | ||
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.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | ViiV Healthcare |
| Phone | 866-435-7343 |
Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00089583
Other Study ID Numbers:
- APV29005
First Posted:
Aug 10, 2004
Last Update Posted:
Mar 7, 2017
Last Verified:
Jan 1, 2017