A Clinical Study Of An Investigational Regimen Including Marketed HIV Drugs In HIV-1 Pediatric Subjects Ages 2-18 Years
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: ritonavir; fosamprenavir
Intervention description: ritonavir oral capsules or oral solution; fosamprenavir oral suspension or tablet
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: 69.0
Sex: All
Minimum age: 2 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: pediatrics; HIV; protease inhibitors; ritonavir; fosamprenavir; LEXIVA; AGENERASE; amprenavir

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.
    

Eligibility 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).