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HIV InfectionPhase 2NCT00040664

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

A Phase 2 study testing ritonavir and fosamprenavir in people with HIV Infection, run by ViiV Healthcare at 42 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 2 to 18 years
Conditions the study is for
HIV Infection
What is being tested?
ritonavir and fosamprenavir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
42 sitesin 7 countries
Study dates
Jul 2002to Oct 2008
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

  • 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)
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  • 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)

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

42 sites in 7 countries.

42 sites in 7 countries

United States17 sites
  • GSK Investigational Site

    Birmingham, Alabama, 35233

  • GSK Investigational Site

    Boston, Massachusetts, 02118

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599-7220

  • GSK Investigational Site

    Chicago, Illinois, 60614

  • GSK Investigational Site

    Cleveland, Ohio, 44106

  • GSK Investigational Site

    Dallas, Texas, 75235

  • GSK Investigational Site

    Durham, North Carolina, 27705

  • GSK Investigational Site

    Fort Worth, Texas, 76104

  • GSK Investigational Site

    Jacksonville, Florida, 32209

  • GSK Investigational Site

    Los Angeles, California, 90027

  • GSK Investigational Site

    New Orleans, Louisiana, 70112

  • GSK Investigational Site

    New York, New York, 10016

  • GSK Investigational Site

    New York, New York, 10021

  • GSK Investigational Site

    Richmond, Virginia, 23298

  • GSK Investigational Site

    Stony Brook, New York, 11794-8111

  • GSK Investigational Site

    Tampa, Florida, 33613

  • GSK Investigational Site

    The Bronx, New York, 10457

Other trials in United States

Spain9 sites
  • GSK Investigational Site

    Barcelona, 08003

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08950

  • GSK Investigational Site

    Madrid, 28007

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Madrid, 28047

  • GSK Investigational Site

    Palma de Mallorca, 07014

  • GSK Investigational Site

    Seville, 41013

  • GSK Investigational Site

    Valencia, 46009

Other trials in Spain

Italy8 sites
  • GSK Investigational Site

    Florence, Tuscany, 55100

  • GSK Investigational Site

    Genoa, Liguria, 16132

  • GSK Investigational Site

    Milan, Lombardy, 20122

  • GSK Investigational Site

    Milan, Lombardy, 20142

  • GSK Investigational Site

    Modena, Emilia-Romagna, 41150

  • GSK Investigational Site

    Padova, Veneto, 35128

  • GSK Investigational Site

    Pavia, Lombardy, 27100

  • GSK Investigational Site

    Rome, Lazio, 00165

Other trials in Italy

Portugal3 sites
  • GSK Investigational Site

    Amadora, 2700

  • GSK Investigational Site

    Lisbon, 1150

  • GSK Investigational Site

    Lisbon, 1649-035

Other trials in Portugal

Canada2 sites
  • GSK Investigational Site

    Montreal, Quebec, H3T 1C5

  • GSK Investigational Site

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Romania2 sites
  • GSK Investigational Site

    Bucharest, 021105

  • GSK Investigational Site

    Bucharest, 030303

Other trials in Romania

Netherlands1 site
  • GSK Investigational Site

    Rotterdam, 3015 GE

Other trials in Netherlands

About this 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 Experienced, Pediatric Subjects 2-18 Years Old

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.

Read the 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

Conditions
HIV Infection
Being tested
ritonavir, fosamprenavir
Keywords
pediatrics, HIV, protease inhibitors, ritonavir, fosamprenavir, LEXIVA, AGENERASE, amprenavir
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ritonavirDrug

    Also called fosamprenavir

    ritonavir oral capsules or oral solution

  • fosamprenavirDrug

    fosamprenavir oral suspension or tablet

Study groups in NCT00040664
Study groupRoleWhat they receive
2 to 5 years (FPV/RTV)ExperimentalTwo 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)
Receives: Drug: ritonavir; Drug: fosamprenavir
6 to 11 years (FPV/RTV)ExperimentalSix 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)
Receives: Drug: ritonavir; Drug: fosamprenavir
12 to 18 years (FPV/RTV)ExperimentalTwelve 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)
Receives: Drug: ritonavir; Drug: fosamprenavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Discontinued Treatment Due to Adverse Events

    The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.

    Measured: Baseline through end of study (at least Week 168)

  2. Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event

    The number of participants with drug-related adverse events coded as Grade 2 (mild), Grade 3 (severe), or Grade 4 (life-threatening).

    Measured: Baseline through end of study (at least Week 168)

  3. Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities

    The number of participants with Grade 3 (severe) or Grade 4 (life-threatening) laboratory abnormalities while on study treatment.

    Measured: Baseline through end of study (at least Week 168)

  4. Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  5. Geometric Mean of Steady State Plasma APV Parameter: Cmax

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  6. Median Steady State Plasma APV Tmax

    tmax: time after administration of the drug when maximum concentration is reached

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  7. Geometric Mean of Steady State Plasma APV Parameter: CL/F

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  8. Geometric Mean of Steady State Plasma APV Parameter: t1/2

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  9. Least Squares Mean of Plasma APV Parameter: AUC0-tau

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

  10. Least Squares Mean of Plasma APV Parameter: Cmax

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

  11. Least Squares Mean of Plasma APV Parameter: Ctau

    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.

    Measured: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

Secondary outcomes (4)
  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)

    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.

    Measured: Weeks 12, 48, 96, and 168

  2. Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits

    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.

    Measured: Baseline and Weeks 12, 48, 96, and 168

  3. Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits

    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.

    Measured: Baseline and Weeks 12, 48, 96, and 168

  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

    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.

    Measured: Time of virologic failure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2002 (estimated)
  2. Study startJul 2002
  3. Primary completionOct 2008
  4. Study completionOct 2008

Resources

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
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00040664
Sponsor's protocol ID
APV 20003
Status last verified
Jan 2017
First submitted
5 Jul 2002
Last updated
3 Mar 2017

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ritonavir and fosamprenavir in people with HIV Infection, run by ViiV Healthcare at 42 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 14 inclusion and 17 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 3 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 42 sites in United States, Spain, Italy, Portugal, Canada 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 23 Feb 2010). 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?

Number of Participants Who Discontinued Treatment Due to Adverse Events (time frame: Baseline through end of study (at least Week 168)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 3 Mar 2017.

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