Pharmacokinetics and Safety Study of Tipranavir in Combination With Low Dose Ritonavir in Human Immunodeficiency Virus (HIV)-Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: TPV oral solution; TPV oral solution; RTV oral solution; RTV oral solution
Intervention description: Tipranavir oral solution; Tipranavir oral solution; Ritonavir oral solution; Ritonavir oral solution
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 2 Years
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to assess the safety and tolerability of tipranavir
      (TPV) oral formulation and soft gelatin capsules together with low-dose ritonavir in
      HIV-infected children and adolescents, to provide information concerning the pharmacokinetic
      characteristics of tipranavir and ritonavir in this age group, and to determine the relative
      bioavailability of the TPV liquid formulation and TPV capsule formulation in adolescents
      switching from liquid to capsule.

      The secondary objective of this study is the determination of the dose of topranavir and
      ritonavir (TPV/r) in children and adolescents between 2 and 18 years of age required for an
      adult equivalent systemic exposure of TPV/r 500 mg / 200 mg.
    

Eligibility criteria:

        Inclusion criteria:

          1. Males and females between 2 and 18 years of age.

          2. A confirmed diagnosis of HIV-1 infection as defined by two positive assays from two
             different samples taken at least two weeks apart. The two results may be any
             combination of the following:

             HIV ribonucleic acid (RNA) detected by reverse transcriptase (RT)-polymerase chain
             reaction(PCR) or HIV proviral deoxyribonucleic acid (DNA) detected by PCR HIV culture
             p24 antigen detection Licensed HIV enzyme-linked immunosorbent assay (ELISA) with
             confirmatory Western blot

          3. Viral load > 1500 RNA copies/mL.

          4. Acceptable screening laboratory values indicative of adequate baseline organ function.
             Laboratory values are considered acceptable if severity is no higher than Grade 1 for
             all tests defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) Table
             for Grading Severity of Pediatric Adverse Experiences (> 3 months of age) with the
             following exceptions:

             Grade 2 gamma-glutamyl transferase Grade 2 cholesterol Grade 2 triglycerides

          5. Signed informed consent prior to study participation from the patient or a legal
             guardian.

             Active assent must be given by the patient if the child and/or adolescent is capable
             of understanding the provided study information (this applies to children with the
             intellectual age of 7 years or greater)

          6. In the opinion of the investigator, an ability to take medications and comply with the
             requirements of the protocol.

        Exclusion criteria:

          1. Female patients of childbearing potential who:

             have a positive serum pregnancy test at screening are breast feeding are planning on
             becoming pregnant are not willing to use two methods of contraception to include at
             least one barrier method (e.g. latex condom plus spermicidal jelly/foam)

          2. Active hepatitis B or C disease defined as hepatitis B surface antigen (HBsAg)
             positivity or hepatitis C (HCV) antibody or RNA positivity with aspartate
             aminotransferase(AST)/ alanine aminotransferase(ALT) > Grade 2.

          3. Life expectancy < 12 months.

          4. Patients who are unwilling to abstain from ingesting contraindicated medications and
             substances which may significantly affect plasma levels of the study medications,
             notably:

             Grapefruit juice or Seville oranges Herbal preparations containing St. John's Wort or
             milk thistle Garlic supplements

          5. Active substance abuse.

          6. Use of investigational medications or vaccines within 28 days before study entry or
             during the trial. Some expanded access antiretroviral medications may be acceptable,
             but must be approved by sponsor.

          7. Requirement for any therapy for malignancy or immunomodulatory drug (e.g. interferon,
             cyclosporine, hydroxyurea, interleukin-2) within 28 days of study entry. Replacement
             intravenous gamma globulin treatment is acceptable.

          8. Any active opportunistic infection within 28 days before study entry or other
             clinically significant findings that may compromise the outcome of the study.

          9. Patients with malabsorption, severe chronic diarrhea or vomiting (more than two
             episodes of moderate or severe intensity, not attributed to medication therapy and
             lasting more than four days) within 28 days of the study.

         10. Evidence or symptoms of encephalopathy or developmental delay that would reduce
             compliance.