A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Nevirapine Immediate Release (IR); Nevirapine Extended Release (XR)
Intervention description: 200 mg Tablet or 50 mg / 5 ml oral suspension; 200 mg, 300 mg or 400 mg Tablet formulation
Intervention MeSH terms: Nevirapine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 3 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The primary objective is to establish the pharmacokinetic (PK) profile at steady state of
      nevirapine XR in HIV infected children from >=3 to <18 years of age. This phase I trial is an
      open-label, multiple dose, non-randomized and cross-over study. Patients who have completed
      the last visit of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP)
      until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved
      and is available by prescription in a given country; or, the patient enrolls in a
      compassionate use program. During this OEP, nevirapine XR safety and efficacy information
      will be collected.
    

Eligibility criteria:

        Inclusion criteria:

          1. Signed and dated written informed consent of a parent or legal guardian prior to
             admission. Active assent must be given by the patient if the child and/or adolescent
             is capable of understanding the provided study information.

          2. HIV-1 infected males or females >= 3 and < 18 years old.

          3. BSA >= 0.58 m2 for patients using BSA to calculate nevirapine IR dose; or BW >= 12.5
             kg for patients using BW to calculate nevirapine IR dose at screening visit.

          4. Treated with a nevirapine IR based regimen for at least 18 weeks prior to screening
             visit (Visit 1); no modifications in the ARV background therapy within the last 2
             weeks prior to screening.

          5. An HIV VL of <50 copies/mL while receiving nevirapine IR at the last measure of VL
             documented in the medical record obtained within a period of 5 months prior to
             screening visit.

          6. An HIV VL of <50 copies/mL at screening visit.

          7. A stable or not decreasing CD4+ cell count according to the investigator's opinion.

          8. Acceptable screening laboratory values that indicate adequate baseline organ function
             according to the opinion of investigator.

          9. ALT and AST <= 2.5 X ULN (DAIDS Grade 1).

         10. Serum creatinine levels <= 1.3 X ULN (DAIDS Grade 1).

         11. Patients able to swallow tablets.

        Exclusion criteria:

          1. Any AIDS-related or AIDS defining illness that is unresolved or not stable on
             treatment at least 8 weeks prior to screening visit.

          2. Diseases other than HIV infection or conditions that, in the investigator's opinion,
             would interfere with the study.

          3. Patients who have been diagnosed with malignant disease and who are receiving systemic
             chemotherapy or are anticipated to receive any therapy during their participation in
             this trial.

          4. Use of investigational medications or vaccines within 28 days prior to Visit 1 or
             during the trial.

          5. Use of immunomodulatory drugs within 28 days before Visit 1 or during the trial (e.g.,
             interferon, cyclosporin, hydroxyurea, interleukin 2).

          6. Concomitant protease inhibitor (PI) treatment.

          7. Unwillingness to abstain from ingesting substances during the study which may alter
             plasma drug concentrations by interaction with the cytochrome P450 system (Appendix
             10.2).

          8. 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 double-barrier methods