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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00040664
Recruitment Status : Completed
First Posted : July 10, 2002
Results First Posted : February 23, 2010
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infection Drug: ritonavir Drug: fosamprenavir Phase 2

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

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Experienced, Pediatric Subjects 2-18 Years Old
Study Start Date : July 2002
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: 2 to 5 years (FPV/RTV)
Two to five years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)
 Drug: ritonavir
ritonavir oral capsules or oral solution
Other Name: fosamprenavir

Drug: fosamprenavir
fosamprenavir oral suspension or tablet
Experimental: 6 to 11 years (FPV/RTV)
Six to twelve years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)
 Drug: ritonavir
ritonavir oral capsules or oral solution
Other Name: fosamprenavir

Drug: fosamprenavir
fosamprenavir oral suspension or tablet
Experimental: 12 to 18 years (FPV/RTV)
Twelve to Eighteen years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)
 Drug: ritonavir
ritonavir oral capsules or oral solution
Other Name: fosamprenavir

Drug: fosamprenavir
fosamprenavir oral suspension or tablet


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants Who Discontinued Treatment Due to Adverse Events [ Time Frame: Baseline through end of study (at least Week 168) ]
    The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.

  2. Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event [ Time Frame: Baseline through end of study (at least Week 168) ]
    The number of participants with drug-related adverse events coded as Grade 2 (mild), Grade 3 (severe), or Grade 4 (life-threatening).

  3. Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities [ Time Frame: Baseline through end of study (at least Week 168) ]
    The number of participants with Grade 3 (severe) or Grade 4 (life-threatening) laboratory abnormalities while on study treatment.

  4. Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau) [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. AUC(0-tau)=area under the concentration curve from time 0 to tau.

  5. Geometric Mean of Steady State Plasma APV Parameter: Cmax [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. Cmax= concentration maximum.

  6. Median Steady State Plasma APV Tmax [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    tmax: time after administration of the drug when maximum concentration is reached

  7. Geometric Mean of Steady State Plasma APV Parameter: CL/F [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. CL/F=apparent plasma clearance.

  8. Geometric Mean of Steady State Plasma APV Parameter: t1/2 [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. t1/2=elimination half-life. t1/2=elimination half-life.

  9. Least Squares Mean of Plasma APV Parameter: AUC0-tau [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4 ]
    A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.

  10. Least Squares Mean of Plasma APV Parameter: Cmax [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4. ]
    A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.

  11. Least Squares Mean of Plasma APV Parameter: Ctau [ Time Frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4. ]
    A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.


Secondary Outcome Measures :
  1. Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis) [ Time Frame: Weeks 12, 48, 96, and 168 ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies per milliliter (mL) at Weeks 12, 48, 96, and 196. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 12, 48, 96, 168 was determined by the TLOVR algorithm with stratification by the six randomization strata. TLOVR analysis categorizes participants by treatment response. Responders were participants with confirmed viral load <400copies/mL on two consecutive visits.

  2. Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits [ Time Frame: Baseline and Weeks 12, 48, 96, and 168 ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 12, 24, 48, 96, and 168. Change from Baseline was defined as the HIV-1 RNA level at Weeks 12, 24, 48, 96, and 168 minus the HIV-1 RNA level at Baseline.

  3. Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits [ Time Frame: Baseline and Weeks 12, 48, 96, and 168 ]
    A blood sample was drawn to determine the CD4+ cell count at Weeks 24, 48, 96, and 168. Change from Baseline was defined as the CD4+ cell count at Weeks 24, 48, 96, and 168 minus the CD4+ cell count at Baseline.

  4. Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline [ Time Frame: Time of virologic failure ]
    A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of virologic failure were tabulated by drug class. Virologic failure is defined as HIV-1 RNA greater than or equal to 400 copies/mL.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:
  • 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 > or =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 amprenavir.
  • 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 lactating.
  • 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 1993/1994 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, propafenone, 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
  • 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00040664


Locations
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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
Bronx, New York, United States, 10457
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
New York, New York, United States, 10021
GSK Investigational Site
Stony Brook, New York, United States, 11794-8111
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7220
GSK Investigational Site
Durham, North Carolina, United States, 27705
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
GSK Investigational Site
Modena, Emilia-Romagna, Italy, 41150
GSK Investigational Site
Roma, Lazio, Italy, 00165
GSK Investigational Site
Genova, Liguria, Italy, 16132
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Milano, Lombardia, Italy, 20142
GSK Investigational Site
Pavia, Lombardia, Italy, 27100
GSK Investigational Site
Firenze, Toscana, Italy, 55100
GSK Investigational Site
Padova, Veneto, Italy, 35128
Netherlands
GSK Investigational Site
Rotterdam, Netherlands, 3015 GE
Portugal
GSK Investigational Site
Amadora, Portugal, 2700
GSK Investigational Site
Lisboa, Portugal, 1150
GSK Investigational Site
Lisboa, Portugal, 1649-035
Romania
GSK Investigational Site
Bucharest, Romania, 021105
GSK Investigational Site
Bucharest, Romania, 030303
Spain
GSK Investigational Site
Barcelona, Spain, 08003
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Barcelona, Spain, 08950
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Madrid, Spain, 28047
GSK Investigational Site
Palma de Mallorca, Spain, 07014
GSK Investigational Site
Sevilla, Spain, 41013
GSK Investigational Site
Valencia, Spain, 46009
Sponsors and Collaborators
ViiV Healthcare
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Layout table for additonal information
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00040664    
Other Study ID Numbers: APV 20003
First Posted: July 10, 2002    Key Record Dates
Results First Posted: February 23, 2010
Last Update Posted: March 3, 2017
Last Verified: January 2017
Keywords provided by ViiV Healthcare:
pediatrics
HIV
protease inhibitors
ritonavir
 fosamprenavir
LEXIVA
AGENERASE
amprenavir
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
 Fosamprenavir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors