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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00905489
First received: May 6, 2009
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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


Condition Intervention Phase
HIV Infections
Drug: Nevirapine extended release
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multiple Dose PK Study of Nevirapine XR in HIV-1 Infected Children

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary endpoints will be morning trough Cpre,N. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics: AUCt,ss; Cmin,ss; Cmax,ss; Cmax,ss/Cmin,ss ratio; PTF; tmax,ss; CL/F,ss; Cavg. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Safety: Occurrence of significant changes from baseline laboratory measurements and adverse events. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Efficacy: Patients maintaining a VL < 50 and <400 copies/mL at Day 22 and Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 86
Study Start Date: June 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nevirapine Immediate Release
Patients receive nevirapine immediate release either suspension or 200 mg tablets BID according to the VIRAMUNE approved label.
Drug: Nevirapine extended release
100 mg or 400 mg Tablet formulation
Experimental: Nevirapine Extended Release
Since this is a PK cross-over design trial, patients receiving nevirapine immediate release are switched to nevirapine extended release 200 mg, 300 mg or 400 mg QD.
Drug: Nevirapine extended release
100 mg or 400 mg Tablet formulation

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00905489

Locations
United States, District of Columbia
1100.1518.0001 Boehringer Ingelheim Investigational Site
Washington, District of Columbia, United States
United States, Pennsylvania
1100.1518.0002 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
Botswana
1100.1518.2605 Boehringer Ingelheim Investigational Site
Francistown, Botswana
1100.1518.2603 Boehringer Ingelheim Investigational Site
Gaborone, Botswana
1100.1518.2601 Boehringer Ingelheim Investigational Site
Gaborone, Botswana
Germany
1100.1518.4902 Boehringer Ingelheim Investigational Site
Berlin, Germany
1100.1518.4901 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1100.1518.4903 Boehringer Ingelheim Investigational Site
München, Germany
South Africa
1100.1518.2702 Boehringer Ingelheim Investigational Site
Cape Town, South Africa
1100.1518.2703 Boehringer Ingelheim Investigational Site
Parow Valley, South Africa
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00905489     History of Changes
Other Study ID Numbers: 1100.1518, 2008-005855-61
Study First Received: May 6, 2009
Last Updated: February 6, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Republic of Botswana: Ministry of Health
South Africa: MCC (Medicines Control Council)
United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Nevirapine
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014