Infection, Human Immunodeficiency Virus IPhase 2NCT00089583
48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection
A Phase 2 study testing LEXIVA (GW433908) and Ritonavir in people with Infection, Human Immunodeficiency Virus I, run by ViiV Healthcare at 39 sites in 7 countries.
Trial 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 . Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Infection, Human Immunodeficiency Virus I
- What is being tested?
- LEXIVA (GW433908) and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 39 sitesin 7 countries
- Study dates
- Jul 2004to Jul 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 13Show fewer
- 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
Who cannot join
- 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.
Show all 19Show fewer
- 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
Trial locations and contacts
39 sites in 7 countries.
39 sites in 7 countries
United States16 sites
GSK Investigational Site
Birmingham, Alabama, 35233
GSK Investigational Site
Boston, Massachusetts, 02115-5724
GSK Investigational Site
Boston, Massachusetts, 02118
GSK Investigational Site
Dallas, Texas, 75235
GSK Investigational Site
Durham, North Carolina, 27710
GSK Investigational Site
Fort Worth, Texas, 76104
GSK Investigational Site
Jacksonville, Florida, 32209
GSK Investigational Site
Los Angeles, California, 90033
GSK Investigational Site
New Hyde Park, New York, 11042
GSK Investigational Site
New York, New York, 10016
GSK Investigational Site
New York, New York, 10021
GSK Investigational Site
New York, New York, 10037
GSK Investigational Site
Oakland, California, 94609
GSK Investigational Site
Philadelphia, Pennsylvania, 19134
GSK Investigational Site
Tampa, Florida, 33606
GSK Investigational Site
The Bronx, New York, 10457
Spain9 sites
GSK Investigational Site
Barcelona, 08003
GSK Investigational Site
Barcelona, 08950
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Madrid, 28046
GSK Investigational Site
Málaga, 29010
GSK Investigational Site
Palma de Mallorca, 07014
GSK Investigational Site
Seville, 41013
GSK Investigational Site
Valencia, 46009
GSK Investigational Site
Vigo ( Pontevedra), 36204
Canada4 sites
GSK Investigational Site
Montreal, Quebec, H3T 1C5
GSK Investigational Site
Toronto, Ontario, M5G 1X8
GSK Investigational Site
Vancouver, British Columbia, V6H 3N1
GSK Investigational Site
Winnipeg, Manitoba, R3E 3P4
South Africa4 sites
GSK Investigational Site
Coronationville, Gauteng, 2112
GSK Investigational Site
Durban, KwaZulu-Natal, 4013
GSK Investigational Site
Parow Valley, Western Province, 7505
GSK Investigational Site
Soweto, 2013
Russia3 sites
GSK Investigational Site
Moscow, 105275
GSK Investigational Site
Moscow, 129110
GSK Investigational Site
Saint Petersburg, 196645
Romania2 sites
GSK Investigational Site
Bucharest, 021105
GSK Investigational Site
Bucharest, 030303
About this study
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
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 .
Read the 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
- Being tested
- LEXIVA (GW433908), Ritonavir
- Keywords
- antiretroviral therapy, pediatrics, AGENERASE, amprenavir, fosamprenavir, HIV Infection, ritonavir, protease inhibitor, LEXIVA
- Medical subject headings
- Infections, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEXIVA (GW433908)Drug
Fosamprenavir suspension or tablet bid
RitonavirDrug
Also called LEXIVA (GW433908)
Ritonavir solution bid
| Study group | Role | What they receive |
|---|---|---|
| 2 - 18 yrs old (FPV/RTV BID) | Experimental | 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) Receives: Drug: LEXIVA (GW433908); Drug: Ritonavir |
| 2 - less than 6yrs old (FPV BID) | Experimental | Cohort 1A - 2 - less than 6yrs old (FPV BID) Receives: Drug: LEXIVA (GW433908) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Amprenavir (APV) AUC (0-tau[τ])
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.
Measured: Week 48
Plasma APV Cmax
The maximum concentration at steady state (Cmax) was measured.
Measured: Week 48
Plasma APV Cτ
The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured.
Measured: Week 48
Plasma APV CL/F Following Dosing Expressed in mg/kg
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.
Measured: Week 48
Plasma APV CL/F Following Dosing Expressed in mg
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).
Measured: Week 48
Plasma APV Tmax
The time to reach the maximum concentration (Cmax) at steady state is defined as tmax.
Measured: Week 48
Plasma APV t1/2
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.
Measured: Week 48
Number of Participants Who Permanently Discontinued the Treatment Due to Any Adverse Event (AE)
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.
Measured: Week 48
Change From Baseline in Triglycerides, Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Serum Glucose at 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.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Serum Lipase at 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.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at 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.
Measured: Baseline (Day 1) and Week 48
Number of Participants With Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Laboratory Abnormalities
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.
Measured: Baseline (Day 1) until Week 48
Secondary outcomes (28)
Plasma Ritonavir (RTV) AUC (0-τ)
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.
Measured: Week 48
Plasma RTV Cmax
The maximum concentration at steady state (Cmax) was measured.
Measured: Week 48
Plasma RTV Cτ
The plasma concentration at the end of the dosing interval at steady-state (Cτ) was measured.
Measured: Week 48
Plasma RTV CL/F Following Dosing Expressed in mg/kg
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.
Measured: Week 48
Plasma RTV CL/F Following Dosing Expressed in mg
Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ).
Measured: Week 48
Plasma RTV Tmax
The time to reach the maximum concentration (Cmax) at steady state is defined as (tmax).
Measured: Week 48
Plasma RTV t1/2
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.
Measured: Week 48
Plasma FPV AUC (0-τ)
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Plasma FPV Cmax and Cτ
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Plasma FPV CL/F Following Dosing Expressed in mg/kg
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Plasma FPV CL/F Following Dosing Expressed in mg
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Plasma FPV Tmax
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Plasma FPV t1/2
The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Measured: Week 48
Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at 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.
Measured: Week 48
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)
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.
Measured: Baseline and Weeks 2, 12, 24, and 48
Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis)
Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA.
Measured: Baseline and Weeks 2, 12, 24, and 48
Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis)
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.
Measured: Baseline and Weeks 2, 12, 24, and 48
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)
Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA.
Measured: Baseline and Weeks 2, 12, 24, and 48
Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at 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.
Measured: Baseline and Weeks 2, 12, 24, and 48
Change From Baseline in CD4+ Cell Count at 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.
Measured: Baseline and Weeks 2, 12, 24, and 48
Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at 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.
Measured: Baseline and Weeks 2, 12, 24, and 48
Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at 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 percentage was calculated as the value at Weeks 2, 12, 24, and 48 minus the value at Baseline.
Measured: Baseline and Week 2, 12, 24, 48
Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease
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.
Measured: Week 48
Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease
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.
Measured: After Week 48 through Week 240
Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS)
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.
Measured: Baseline through 48 Weeks
Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS)
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.
Measured: Week 60 through Week 240
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
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.
Measured: Weeks 2, 12, 24, and 48
Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events
No formal analysis has been performed or is planned to correlate plasma APV PK with efficacy and safety outcomes.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2004 (estimated)
- Study startJul 2004
- Primary completionMar 2011
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infection, Human Immunodeficiency Virus IStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089583
- Sponsor's protocol ID
- APV29005
- Status last verified
- Jan 2017
- First submitted
- 6 Aug 2004
- Last updated
- 7 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
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.
Fortuny C, Duiculescu D, Cheng K, Garges HP, Cotton M, Tamarirt DP, Ford SL, Wire MB, Givens N, Ross LL, Lou Y, Perger T, Sievers J. Pharmacokinetics and 48-week safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2- to 18-year-old children. Pediatr Infect Dis J. 2014 Jan;33(1):50-6. doi: 10.1097/INF.0b013e3182a1126a.
PubMed 23811744
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00089583
- Acronym / sponsor ID
- APV29005
- Keywords
- antiretroviral therapy, pediatrics, AGENERASE, amprenavir, fosamprenavir, HIV Infection, ritonavir, protease inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2004
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 10 Aug 2004 (estimated)
- Results
- Posted 21 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 .
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 - 18 yrs old (FPV/RTV BID) | Experimental | Drug: LEXIVA (GW433908), Drug: RitonavirCohort 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) |
| 2 - less than 6yrs old (FPV BID) | Experimental | Drug: LEXIVA (GW433908)Cohort 1A - 2 - less than 6yrs old (FPV BID) |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- 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:
- 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).
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEXIVA (GW433908)Fosamprenavir suspension or tablet bid | Drug | 2 - 18 yrs old (FPV/RTV BID), 2 - less than 6yrs old (FPV BID) |
| RitonavirAlso: LEXIVA (GW433908)Ritonavir solution bid | Drug | 2 - 18 yrs old (FPV/RTV BID) |
Primary outcome
Plasma Amprenavir (APV) AUC (0-tau[τ])
Time frame: 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
Time frame: Week 48
The maximum concentration at steady state (Cmax) was measured.
Plasma APV Cτ
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 48
The time to reach the maximum concentration (Cmax) at steady state is defined as tmax.
Plasma APV t1/2
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
28 secondary outcomes
Plasma Ritonavir (RTV) AUC (0-τ)
Time frame: Week 48
Plasma RTV Cmax
Time frame: Week 48
Plasma RTV Cτ
Time frame: Week 48
Plasma RTV CL/F Following Dosing Expressed in mg/kg
Time frame: Week 48
Plasma RTV CL/F Following Dosing Expressed in mg
Time frame: Week 48
Plasma RTV Tmax
Time frame: Week 48
Plasma RTV t1/2
Time frame: Week 48
Plasma FPV AUC (0-τ)
Time frame: Week 48
Plasma FPV Cmax and Cτ
Time frame: Week 48
Plasma FPV CL/F Following Dosing Expressed in mg/kg
Time frame: Week 48
Plasma FPV CL/F Following Dosing Expressed in mg
Time frame: Week 48
Plasma FPV Tmax
Time frame: Week 48
Plasma FPV t1/2
Time frame: Week 48
Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48
Time frame: Week 48
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)
Time frame: Baseline and Weeks 2, 12, 24, and 48
Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis)
Time frame: Baseline and Weeks 2, 12, 24, and 48
Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis)
Time frame: Baseline and Weeks 2, 12, 24, and 48
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)
Time frame: Baseline and Weeks 2, 12, 24, and 48
Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 2, 12, 24, and 48
Time frame: Baseline and Weeks 2, 12, 24, and 48
Change From Baseline in CD4+ Cell Count at Weeks 2, 12, 24, and 48
Time frame: Baseline and Weeks 2, 12, 24, and 48
Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Baseline and Weeks 2, 12, 24, and 48
Time frame: Baseline and Weeks 2, 12, 24, and 48
Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Weeks 2, 12, 24, and 48
Time frame: Baseline and Week 2, 12, 24, 48
Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease
Time frame: Week 48
Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease
Time frame: After Week 48 through Week 240
Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS)
Time frame: Baseline through 48 Weeks
Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS)
Time frame: Week 60 through Week 240
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
Time frame: Weeks 2, 12, 24, and 48
Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events
Time frame: Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundVoronin 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.
- BackgroundRoss 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.
- Results publication: PubMed 23811744Fortuny C, Duiculescu D, Cheng K, Garges HP, Cotton M, Tamarirt DP, Ford SL, Wire MB, Givens N, Ross LL, Lou Y, Perger T, Sievers J. Pharmacokinetics and 48-week safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2- to 18-year-old children. Pediatr Infect Dis J. 2014 Jan;33(1):50-6. doi: 10.1097/INF.0b013e3182a1126a.
Related trials for Infection, Human Immunodeficiency Virus I
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis
RecruitingPhase 1
A Study to Investigate Pharmacokinetics, Safety and Tolerability of Long-Acting Cabotegravir Plus Recombinant Human Hyaluronidase PH20 in Healthy Adult Participants
HIV Infections
RecruitingPhase 1/2
Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies ...
HIV, Hematologic Malignancies
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
39 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LEXIVA (GW433908) and Ritonavir in people with Infection, Human Immunodeficiency Virus I, run by ViiV Healthcare at 39 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Spain, Canada, South Africa, Russia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Amprenavir (APV) AUC (0-tau[τ]) (time frame: Week 48). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00089583, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.