A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.

An Open-label, Multiple Dose, Cross-over Study to Evaluate the Steady-state Pharmacokinetic Parameters of Nevirapine Extended Release Tablets in HIV-1 Infected Children, With an Optional Extension Phase

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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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.

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