48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection


Tracking Information

Start Date  ICMJEJuly 2004
Estimated Primary Completion DateDecember 2012   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: November 8, 2007)
Plasma APV Pharmacokinetics Incidence and nature of AEs and laboratory abnormalities Proportion of subjects who permanently discontinue 908/RTV or 908 due to AEs [ Time Frame: 48 Weeks ]
Original Primary Outcome Measures  ICMJE 
 (submitted: January 5, 2006)
Plasma APV Pharmacokinetics; incidence and nature of AEs and laboratory abnormalities; proportion of subjects who permanently discontinue 908/RTV or 908 due to AEs
Change HistoryComplete list of historical versions of study NCT00089583 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: December 11, 2007)
  • Proportions of subjects with vRNA <400copies/mL over time Measured values and changes from baseline in vRNA over time Proportion of subjects with 1.0 log10 copies/mL decrease in vRNA from baseline over time
  • Measured values and changes from baseline in CD4+ cell counts over time Incidence of viral resistance and correlation with outcome Subject adherence to study medications
  • Plasma 908 concentrations Plasma RTV pharmacokinetic parameters Proportion of subjects with vRNA <400 copies/mL over time; changes in CD4+ cell counts over time Subject adherence Incidence of viral resistance [ Time Frame: 48 Weeks ]
  • Plasma FPV concentrations Plasma RTV AUC,ss, Cmax,ss, and C,ss Correlation of plasma APV PK with plasma vRNA, CD4+ cell counts and to the occurrence of AEs
Original Secondary Outcome Measures  ICMJE 
 (submitted: January 5, 2006)
Plasma 908 concentrations; plasma RTV pharmacokinetic parameters; proportion of subjects with vRNA <400 copies/mL over time; changes in CD4+ cell counts over time; subject adherence; incidence of viral resistance

Descriptive Information

Brief Title  ICMJE48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection
Official Title  ICMJESee Detailed 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 .

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 PhasePhase II
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Non-Randomized, Open Label, Parallel Assignment, Safety Study
Condition  ICMJEHIV Infection
Intervention  ICMJE
  • Drug: LEXIVA (GW433908)
  • Drug: Ritonavir
    Other Names:
    • LEXIVA (GW433908)
    • Ritonavir

Recruitment Information

Estimated Enrollment  ICMJE78
Estimated Completion DateDecember 2012
Estimated Primary Completion DateDecember 2012   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
    2. 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 NRTIs and/or 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

  • Must have a viral load greater than or equal to 400 copies/mL.
  • Must be able to take 2-3 other approved HIV medicines during the study.
  • Additional qualifying criteria to be determined by the study physician.

Exclusion criteria:

  • Prior history of having received AGN 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 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
  • Must not have received AGENERASE or the study drug GW433908 for >7 days prior to study start.
  • Must not have received non-nucleoside reverse transcriptase inhibitor (NNRTI) medicines within 14 days before starting study drug or anticipate the need for NNRTIs during the study.
  • Cannot have had certain AIDS related illnesses within 28 days before starting study drug.
  • Cannot be pregnant or breast feeding.
GenderBoth
Ages2 Years to 18 Years
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center877-379-3718
Location Countries  ICMJEUnited States,   Belgium,   Canada,   Romania,   Russian Federation,   South Africa,   Spain

Administrative Information

NCT ID  ICMJENCT00089583
Responsible PartyStudy Director, GSK
Study ID Numbers  ICMJEAPV29005
Study Sponsor  ICMJEGlaxoSmithKline
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:GSK Clinical Trials, MDGlaxoSmithKline
Information Provided ByGlaxoSmithKline