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: May 30, 2014
Last verified: May 2014
  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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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 Immediate Release (IR)
Drug: Nevirapine Extended Release (XR)
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: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Trough Cpre,N. [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Trough Nevirapine concentration immediately prior to the next scheduled dose


Secondary Outcome Measures:
  • AUCt,ss [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of the Nevirapine (NVP) in plasma at steady state over the time dosing interval τ.

    All patients received nevirapine IR for 10 days prior to collection of 12-hour Area Under the Curve (AUC) data. Then, all patients were switched to nevirapine XR for 9 days prior to collection of 24-hour AUC data. The treatments of IR and XR are summarized separately using geometric means and geometric coefficients of variation.

    For NVP IR AUC measured over hours: 0,1,2,3,4,8 and 12, For NVP XR AUC measured over hours: 0,1,2,3,4,8,10,12 and 24.


  • Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Minimum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ by nevirapine XR dose group

  • Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ

  • Ratio Cmax,ss/Cmin,ss [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: Yes ]
    Ratio of (maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ)/(minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ)

  • %PTF [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Percentage peak-trough Nevirapine fluctuation, % fluctuation (degree of peak to trough fluctuation)

  • Tmax,ss [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Time from dosing to the maximum concentration of the Nevirapine in plasma at steady state over the time dosing interval τ

  • CL/F,ss [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Apparent clearance of the Nevirapine in the plasma after extravascular administration at steady-state

  • Cavg [ Time Frame: 10 days for Nevirapine IR, 9 days for Nevirapine XR ] [ Designated as safety issue: No ]
    Average measured concentration of the Nevirapine in plasma at steady state

  • Efficacy: Patients Maintaining a VL < 50 Copies/mL [ Time Frame: Day 504 ] [ Designated as safety issue: Yes ]
    Patients maintaining a viral load < 50 copies/mL at Day 504.

  • Efficacy: Patients Maintaining a VL < 400 Copies/mL [ Time Frame: Day 504 ] [ Designated as safety issue: Yes ]
    Patients maintaining a viral load < 400 copies/mL at Day 504.

  • Change From Baseline in Mean CD4+ Count (Absolute) [ Time Frame: Day 504 ] [ Designated as safety issue: Yes ]
    Change in mean CD4+ count (absolute) from baseline at Day 504.

  • Percentage Change From Baseline in Mean CD4+ Count [ Time Frame: Day 504 ] [ Designated as safety issue: Yes ]
    ((Day 504 value-Baseline value)/Baseline value)*100.


Enrollment: 85
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
Experimental: Nevirapine IR / Nevirapine XR
In this pharmaco-kinetic (PK) cross-over design trial, all patients initially receive nevirapine immediate release and then all patients are switched to nevirapine extended release 200 mg, 300 mg or 400 mg QD. After completing the PK phase patients had the option of continuing treatment with nevirapine XR in the Optional Extension Phase (OEP).
Drug: Nevirapine Immediate Release (IR)
200 mg Tablet or 50 mg / 5 ml oral suspension
Other Name: Nevirapine IR
Drug: Nevirapine Extended Release (XR)
200 mg, 300 mg or 400 mg Tablet formulation
Other Name: Nevirapine XR

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Results First Received: September 23, 2013
Last Updated: May 30, 2014
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 July 28, 2014