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Completed

NCT Number: NCT00905489

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

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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

3 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1100.1518.2605 Boehringer Ingelheim Investigational Site, Francistown, Botswana

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • HIV-1 infected males or females >= 3 and < 18 years old.
  • 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.
  • 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.
  • 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.
  • An HIV VL of <50 copies/mL at screening visit.
  • A stable or not decreasing CD4+ cell count according to the investigator's opinion.
  • Acceptable screening laboratory values that indicate adequate baseline organ function according to the opinion of investigator.
  • ALT and AST <= 2.5 X ULN (DAIDS Grade 1).
  • Serum creatinine levels <= 1.3 X ULN (DAIDS Grade 1).
  • Patients able to swallow tablets.

Exclusion criteria

  • Any AIDS-related or AIDS defining illness that is unresolved or not stable on treatment at least 8 weeks prior to screening visit.
  • Diseases other than HIV infection or conditions that, in the investigator's opinion, would interfere with the study.
  • 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.
  • Use of investigational medications or vaccines within 28 days prior to Visit 1 or during the trial.
  • Use of immunomodulatory drugs within 28 days before Visit 1 or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2).
  • Concomitant protease inhibitor (PI) treatment.
  • 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).
  • 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

Treatment and study plan

Nevirapine Immediate Release (IR)

Drug

200 mg Tablet or 50 mg / 5 ml oral suspension

Other names: Nevirapine IR

Nevirapine Extended Release (XR)

Drug

200 mg, 300 mg or 400 mg Tablet formulation

Other names: Nevirapine XR

Primary outcomes

  1. Trough Cpre,N.

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Trough Nevirapine concentration immediately prior to the next scheduled dose. Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

    The measure of dispersion presented is the coefficient of variation (%) rather than the geometric coefficient of variation.

Secondary outcomes

  1. AUCt,ss

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    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.

  2. Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group)

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Minimum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ by nevirapine XR dose group Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 21.

  3. Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group)

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

  4. Ratio Cmax,ss/Cmin,ss

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    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) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

  5. %PTF

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Percentage peak-trough Nevirapine fluctuation, % fluctuation (degree of peak to trough fluctuation) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

  6. Tmax,ss

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Time from dosing to the maximum concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

    The standard deviation is actually the coefficient of variation.

  7. CL/F,ss

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Apparent clearance of the Nevirapine in the plasma after extravascular administration at steady-state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

  8. Cavg

    Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR

    Average measured concentration of the Nevirapine in plasma at steady state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.

  9. Efficacy: Patients Maintaining a VL < 50 Copies/mL

    Time frame: Day 22

    Patients maintaining a viral load < 50 copies/mL at Day 22.

  10. Efficacy: Patients Maintaining a VL < 400 Copies/mL

    Time frame: Day 22

    Patients maintaining a viral load < 400 copies/mL at Day 22

  11. Change From Baseline in Mean CD4+ Count (Absolute)

    Time frame: Baseline, Day 22 and week 24

    Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24.

  12. Percentage Change From Baseline in Mean CD4+ Count

    Time frame: Baseline to day 22 and baseline to week 24

    ((Day 22 value-Baseline value)/Baseline value)*100. ((Week 24 value-Baseline value)/Baseline value)*100.

  13. Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase

    Time frame: week 24

    Patients maintaining a viral load < 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP).

  14. Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase

    Time frame: week 24

    Patients maintaining a viral load < 400 copies/mL at week 24 of the Optional Extension Phase (OEP)

Other outcomes

  1. Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit

    Time frame: Last available visit, up to 155 weeks

    Patients maintaining a viral load < 50 copies/mL at the last available visit

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
May 20, 2009
Registry last updated
Jan 7, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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