Clinical trial NCT00905489: A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-05-20
Enrollment: 85
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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

Primary outcomes:
measure: Trough Cpre,N.
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Secondary outcomes:
measure: AUCt,ss
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Ratio Cmax,ss/Cmin,ss
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: %PTF
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Tmax,ss
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: CL/F,ss
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Cavg
timeFrame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
measure: Efficacy: Patients Maintaining a VL < 50 Copies/mL
timeFrame: Day 22
measure: Efficacy: Patients Maintaining a VL < 400 Copies/mL
timeFrame: Day 22
measure: Change From Baseline in Mean CD4+ Count (Absolute)
timeFrame: Baseline, Day 22 and week 24
measure: Percentage Change From Baseline in Mean CD4+ Count
timeFrame: Baseline to day 22 and baseline to week 24
measure: Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase
timeFrame: week 24
measure: Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase
timeFrame: week 24
Other outcomes:
measure: Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit
timeFrame: Last available visit, up to 155 weeks
Locations:
city: Washington
country: United States
facility: 1100.1518.0001 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Philadelphia
country: United States
facility: 1100.1518.0002 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Francistown
country: Botswana
facility: 1100.1518.2605 Boehringer Ingelheim Investigational Site
city: Gaborone
country: Botswana
facility: 1100.1518.2601 Boehringer Ingelheim Investigational Site
city: Gaborone
country: Botswana
facility: 1100.1518.2603 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1100.1518.4902 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1100.1518.4901 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1100.1518.4903 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1100.1518.2702 Boehringer Ingelheim Investigational Site
city: Parow Valley
country: South Africa
facility: 1100.1518.2703 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: