48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection
Condition: Infection, Human Immunodeficiency Virus I
MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: LEXIVA (GW433908); Ritonavir
Intervention description: Fosamprenavir suspension or tablet bid; Ritonavir solution bid
Intervention MeSH terms: Ritonavir; Fosamprenavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 2 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: antiretroviral therapy; pediatrics; AGENERASE; amprenavir; fosamprenavir; HIV Infection; ritonavir; protease inhibitor; LEXIVA

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 .
    

Eligibility criteria:

        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 Nucleoside Reverse Transcriptase
        Inhibitors (NRTIs) and/or Non-Nucleoside Reverse Transcriptase Inhibitors (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

        Exclusion criteria:

          -  Prior history of having received APV 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 Centers for Disease Control and Prevention
             (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