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

Sponsor:	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 Infection	Drug: ritonavir Drug: fosamprenavir	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety Study
Official Title:	See Detailed Description

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium

U.S. FDA Resources

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:

Proportion of subjects with plasma HIV-1 RNA levels <400 copies/mL at each study visitChange from baseline in plasma HIV-RNA at each study visit (absolute values and time averaged) [ Time Frame: 48 Weeks ]
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) [ Time Frame: 48 Weeks ]
Proportion of switch subjects who permanently discontinue GW433908/RTV twice daily due to adverse events [ Time Frame: 48 Weeks ]
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 eventsSubject adherence, shaking of GW433908 oral suspension and parent/guardian perceptions of study medication [ Time Frame: 48 Weeks ]

Enrollment:	69
Study Start Date:	July 2002
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Fosamprenavir/ritonavir: Experimental	Drug: ritonavir ritonavir oral capsules Drug: fosamprenavir fosamprenavir oral suspension or tablet

Detailed Description:

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

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:
a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
b. 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, ardiac 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

Hide Study Locations

Locations

United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35233
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90027
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32209
GSK Investigational Site
Tampa, Florida, United States, 33613
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60614
United States, Louisiana
GSK Investigational Site
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02118
United States, New York
GSK Investigational Site
New York, New York, United States, 10021
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
Bronx, New York, United States, 10457
GSK Investigational Site
Stony Brook, New York, United States, 11794-8111
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7220
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44106
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75235
GSK Investigational Site
Fort Worth, Texas, United States, 76104
United States, Virginia
GSK Investigational Site
Richmond, Virginia, United States, 23298
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H3T 1C5
Italy, Emilia-Romagna
GSK Investigational Site
Modena, Emilia-Romagna, Italy, 41150
Italy, Lazio
GSK Investigational Site
Roma, Lazio, Italy, 00165
Italy, Liguria
GSK Investigational Site
Genova, Liguria, Italy, 16132
Italy, Lombardia
GSK Investigational Site
Milano, Lombardia, Italy, 20142
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Pavia, Lombardia, Italy, 27100
Italy, Toscana
GSK Investigational Site
Firenze, Toscana, Italy, 55100
Italy, Veneto
GSK Investigational Site
Padova, Veneto, Italy, 35128
Netherlands
GSK Investigational Site
ROTTERDAM, Netherlands, 3015 GE
Portugal
GSK Investigational Site
Lisboa, Portugal, 1150
GSK Investigational Site
Amadora, Portugal, 2700
GSK Investigational Site
Lisboa, Portugal, 1649-035
Romania
GSK Investigational Site
Bucharest, Romania, 030303
GSK Investigational Site
Bucharest, Romania, 021105
Spain
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Barcelona, Spain, 08950
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Madrid, Spain, 28047
GSK Investigational Site
Valencia, Spain, 46009
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Sevilla, Spain, 41013
GSK Investigational Site
Barcelona, Spain, 08003
GSK Investigational Site
Palma de Mallorca, Spain, 07014

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	APV 20003
Study First Received:	July 5, 2002
Last Updated:	May 15, 2009
ClinicalTrials.gov Identifier:	NCT00040664 History of Changes
Health Authority:	Canada: Health Canada; Italy: The Italian Medicines Agency; Spain: Spanish Agency of Medicines; United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

pediatrics
HIV
protease inhibitors
ritonavir

fosamprenavir
LEXIVA
AGENERASE
amprenavir

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
Fosamprenavir
HIV Infections
Ritonavir
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on November 27, 2009