E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected children under antiretroviral therapy |
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E.1.1.1 | Medical condition in easily understood language |
Children who are infected with HIV-1 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the pharmacokinetic (PK) parameters at steady-state of once-daily (QD) nevirapine (NVP) extended release (XR) in children aged 3 to 17 years under fasting conditions. |
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E.2.2 | Secondary objectives of the trial |
Safety, tolerability and efficacy of nevirapine extended release. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent of a parent or legal guardian prior to admission to the study in accordance with GCP and the local laws and regulations. Active assent must be given by the patient if the child and/or adolescent is capable of understanding the provided study information [based on the local laws and regulations of each country and site]. 2. HIV-1 infected males or females ≥ 3 and < 18 years old. Final, BI Trial No.: Trial Protocol Page Boehringer Ingelheim 4 Dec 2008 1100.1518 28 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, and the expectancy to stay under the same antiviral regimen for at least 30 weeks. 5. An HIV viral load 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 viral load 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 investigator’s opinion. 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. |
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E.4 | Principal 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 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 (simultaneous use of two different methods such as diaphragm with spermicidal substance and condom) of contraception, or require ethinyl estradiol administration. Barrier methods of contraception include diaphragm with spermicidal substance, cervical caps and condoms. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints will be morning trough Cpre,N, AUCτ,ss, Cmin,ss and Cmax,ss. • Cpre,N (trough drug concentration immediately prior to the next scheduled dose) • AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time dosing interval τ) • Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) • Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completion of day study day 22 |
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E.5.2 | Secondary end point(s) |
Cmax,ss /Cmin,ss, %PTF, tmax,ss, CL/F,ss, and Cavg will be reported as descriptive statistics. The following three efficacy endpoints will be analyzed descriptively: 1. Proportion of patients maintaining a viral load < 50 copies/mL at Day 22 and Week 24, 2. Proportion of patients maintaining a viral load < 400 copies/mL at Day 22 and Week 24, 3. Change in mean CD4 count (absolute and percentage) from baseline at Day 22 and Week 24. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of day study day 22 and after completion of optional extension if applicable |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Botswana |
Germany |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Already provided in the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |