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

This study is currently recruiting participants.
Verified by GlaxoSmithKline, December 2007

Sponsored by: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00040664
  Purpose

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


Condition Intervention Phase
HIV Infections
Drug: fosamprenavir
Drug: ritonavir
Phase II

MedlinePlus related topics:   AIDS   

Drug Information available for:   Ritonavir    VX 478    Fosamprenavir    Fosamprenavir calcium    Fosamprenavir sodium   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety Study
Official Title:   A 48 Week, Phase II, Open-Label, Multi-Cohort, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GW433908/Ritonavir QD and GW433908/Ritonavir BID When Administered to HIV-1 Infected, Antiretroviral Naive and Experience Pediatric Subjects 2 to 18 Years Old

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Proportion of subjects who permanently discontinue GW433908/RTV (ritonavir) due to adverse events; incidence and nature of AEs in study subjects; plasma APV (amprenavir)pharmacokinetic parameters [ Time Frame: 48 Weeks ]

Secondary Outcome Measures:
  • Plasma GW433908 concentrations; Plasma RTV pharmacokinetic parameters; incidence of viral resistance; subject adherence; proportions of subjects with viral load <400 copies/mL at each study visit; change from baseline in CD4+ cell count [ Time Frame: 48 Weeks ]
  • Correlation of plasma APV PK with plasma HIV-1 RNA concentrations, CD4+ cell counts and to the occurrence of adverse events Subject adherence, shaking of GW433908 oral suspension and parent/guardian perceptions of study medication
  • Proportion of subjects with plasma HIV-1 RNA levels <400 copies/mL at each study visit Change from baseline in plasma HIV-RNA at each study visit (absolute values and time averaged)
  • Proportion of subjects with > 1.0 log 10 decrease in plasma HIV-1 RNA at each study visit Change from baseline in CD4+ cell count at each study visit (absolute values and time averaged)
  • Proportion of switch subjects who permanently discontinue GW433908/RTV twice daily due to adverse events

Estimated Enrollment:   62
Study Start Date:   April 2002
Estimated Study Completion Date:   September 2008

  Eligibility
Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  • Parent or legal guardian (and study patient if possible) has the ability to understand what is required of the patient in the study, what will occur during the study, and provide written informed consent to participate.
  • Screening lab result of plasma HIV-1 RNA greater than or equal to 400 copies/mL.
  • Must be able to use 2 nucleoside reverse transcriptase inhibitors as a background regimen.
  • Male or females 2 to < 18 years of age
  • A female is eligible to enter and participate in this study if she is of:

    1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
    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). Note: hormonal contraceptives are not considered a sufficient form of contraceptive for this study.

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

Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide) Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion) Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year. All subjects participating in this study should be counselled on the practice of safe/safer sex.

  • Parent or legal guardian (and subject whenever possible) has the ability to understand and provide written informed consent for the subject to participate in the trial. Verbal witnessed assent must be obtained from the subject whenever possible.
  • Screening plasma HIV-1 RNA >400copies/mL.
  • Subject's who, in the investigator's opinion, and following resistance testing where appropriate, are able to construct an active NRTI backbone regimen consisting of 2 NRTIs. - Subjects must meet one of the following criteria:

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

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

  • Exclusion Criteria:
  • Prior history of having received AGENERASE.
  • Use of non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy within 14 days of study Day 1 or anticipated need for concurrent NNRTI therapy during the study period.
  • Have had an AIDS defining illness (acute CDC Category C event) within 28 days of screening.
  • Pregnant or breast-feeding.
  • Prior history of having received FPV.
  • Non-nucleoside reverse transcriptase inhibitor therapy within 14 days prior to study drug administration or anticipated need for concurrent NNRTI therapy during the study period.
  • Subjects who, in the investigator's opinion, are not able to comply with the requirements of the study.
  • An acute CDC Category C event (per 11993/1994 classification) and/or serious bacterial infection(s) within 28 days prior to study drug administration.
  • Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the subject unable to take oral medication.
  • Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia,diabetes, cardiac dysfunction and hepatitis) which, in the opinion of the investigator, might compromise the safety of the subject.
  • Current grade 2 or higher serum lipase within 28 days prior to study drug administration and/or history of clinically relevant pancreatitis within the previous 6 months. - Grade 3 or 4 transaminase levels (ALT and/or AST) within 28 days prior to study drug administration and/or clinically relevant hepatitis within the previous 6 months..
  • Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days of study drug administration or an anticipated need for such treatment within the study period.
  • Treatment with immunomodulating agents (e.g., systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (e.g., hydroxyurea or foscarnet) within 28 days of study drug administration.
  • Treatment with any of the following medications within 28 days prior to receiving study medication or the anticipated need during the study:

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

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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00040664

Show 47 study locations  Show 47 Study Locations

Sponsors and Collaborators
GlaxoSmithKline

Investigators
Study Director:     GSK Clinical Trials, MD     GlaxoSmithKline    
  More Information


Study ID Numbers:   APV 20003
First Received:   July 5, 2002
Last Updated:   December 11, 2007
ClinicalTrials.gov Identifier:   NCT00040664
Health Authority:   United States: Food and Drug Administration;   Canada: Health Canada;   Spain: Spanish Agency of Medicines;   Italy: The Italian Medicines Agency

Keywords provided by GlaxoSmithKline:
pediatrics  
HIV  
protease inhibitors  
ritonavir  
fosamprenavir
LEXIVA
AGENERASE
amprenavir

Study placed in the following topic categories:
Virus Diseases
Amprenavir
Sexually Transmitted Diseases, Viral
Fosamprenavir
Ritonavir
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
HIV Protease Inhibitors
Slow Virus Diseases
Anti-HIV Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections

ClinicalTrials.gov processed this record on November 20, 2008




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