A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00905489
- Lead Sponsor
- Boehringer Ingelheim
- 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of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program.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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 85
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Nevirapine IR / Nevirapine XR Nevirapine Immediate Release (IR) 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). Nevirapine IR / Nevirapine XR Nevirapine Extended Release (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).
- Primary Outcome Measures
Name Time Method Trough Cpre,N. 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 Outcome Measures
Name Time Method AUCt,ss 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.Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) 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.
Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) 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.
Ratio Cmax,ss/Cmin,ss 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.
%PTF 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.
Tmax,ss 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.CL/F,ss 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.
Cavg 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.
Efficacy: Patients Maintaining a VL < 50 Copies/mL Day 22 Patients maintaining a viral load \< 50 copies/mL at Day 22.
Efficacy: Patients Maintaining a VL < 400 Copies/mL Day 22 Patients maintaining a viral load \< 400 copies/mL at Day 22
Change From Baseline in Mean CD4+ Count (Absolute) Baseline, Day 22 and week 24 Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24.
Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase week 24 Patients maintaining a viral load \< 400 copies/mL at week 24 of the Optional Extension Phase (OEP)
Percentage Change From Baseline in Mean CD4+ Count 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.
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase week 24 Patients maintaining a viral load \< 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP).
Trial Locations
- Locations (10)
1100.1518.2703 Boehringer Ingelheim Investigational Site
🇿🇦Parow Valley, South Africa
1100.1518.0001 Boehringer Ingelheim Investigational Site
🇺🇸Washington, District of Columbia, United States
1100.1518.0002 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1100.1518.2601 Boehringer Ingelheim Investigational Site
🇧🇼Gaborone, Botswana
1100.1518.2605 Boehringer Ingelheim Investigational Site
🇧🇼Francistown, Botswana
1100.1518.2603 Boehringer Ingelheim Investigational Site
🇧🇼Gaborone, Botswana
1100.1518.4903 Boehringer Ingelheim Investigational Site
🇩🇪München, Germany
1100.1518.4902 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1100.1518.2702 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1100.1518.4901 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt/Main, Germany