E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
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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 obtain steady-state pharmacokinetics of TMC125 b.i.d in treatment-experienced HIV-1 infected children; - to obtain dose recommendations of TMC125 per body weight in treatment-experienced HIV-1 infected children ≥ 6 years old and weighing ≥ 20 kg. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate short-term safety and tolerability of TMC125 b.i.d. in treatment-experienced HIV-1 infected children. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Boys and girls ≥ 6 and ≤ 17 years old. 2. Subjects with documented HIV-1 infection. 3. Subjects weighing ≥ 20 kg and with weight < P90 according to the CDC growth charts 4. Being able to swallow the TMC125 tablet(s). 5. Subjects currently on a stable regimen of least 2 NRTIs and LPV/rtv with or without ENF (at approved pediatric doses) for at least 2 months who are not expected to change their regimen in the next 15 days and with a VL < 50 copies/mL on 2 consecutive determinations (last VL measurement in medical file + screening VL measurement, should be taken at least 1 month apart). 6. Parents or legal representative and trial subjects (where appropriate, depending on age and local regulation) willing and able to give consent. Children will be informed about the trial, and asked to give positive assent 7. Subjects can comply with the protocol requirements. Parents or legal representatives of the subjects will be instructed by the investigator to adequately supervise the subject’s protocol adherence. 8. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. 9. Sexually active boys, or girls who are sexually active and able to become pregnant, must either practice sexual abstinence during the trial or use a safe and effective birth control method such as a double barrier method of contraception (i.e., using a condom with either spermicidal cream/foam/gel or diaphragm or cervical cap) or hormone-based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap with spermicide or female condom with spermicide) during the trial. Hormonal birth control alone is not considered to be adequate. Note: Spermicides containing non-oxynol-9 should not be used as this can potentially increase the rate of HIV-1 transmission. 10. Non-smoking or smoking no more than 10 cigarettes per day for at least 3 months prior to selection. |
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E.4 | Principal exclusion criteria |
1. Use of disallowed concomitant therapy 2. History or current use of alcohol (more than 2 units per day), barbiturates, amphetamines, recreational or narcotic drugs, which in the investigator’s opinion would compromise the subject’s safety and/or compliance with the trial procedures. 3. Life expectancy of less than 6 months according to the judgment of the investigator. 4. Presence of any currently active AIDS defining illness (Catergory C conditions according to the CDC Classification System for HIV Infection 1993 or according to the 1994 revised CDC Classification System for HIV Infection in Children less than 13 years of age Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered as currently active. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in cases where the medication administered is not part of the disallowed medications 5. Any active clinically significant disease (e.g. TB, malignancies, cardiac dysfunction, pancreatitis, acute bacterial or viral infections) or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subject’s safety or outcome of the trial. 6. Subjects with history or at risk of bleeding disorders. 7. Acute and/or chronic viral hepatitis including but not limited to A, B, or C (confirmed by hepatitis A antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) at screening. 8. Receipt of an investigational drug within 30 days prior to the trial drug administration. 9. Previously demonstrated clinically significant allergy or hypersensitivity to TMC125 or any of the excipients of the investigational medication administered in this trial. 10. Any history of significant ARV drug rash requiring permanent drug discontinuation or other clinically significant drug allergy, drug rash, eruptions or urticaria. 11. Pregnancy or breastfeeding. 12. Any grade 3 or grade 4 toxicity according to the Division of AIDS (DAIDS) grading scale Note: Retesting of abnormal screening values that lead to exclusion will be allowed only once using an unscheduled visit during the screening period (to reassess eligibility). 13. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (International Normalized Ratio [INR]> 1.5 or albumin < 30 g/L or bilirubin > 2.5 x ULN). 14. A positive urine drug test at screening. Urine will be tested to check the current use of amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids. 15. Currently significant diarrhea, gastric stasis, or constipation that in the investigator’s opinion could influence drug absorption or bioavailability. 16. Having developed rash, erythema, or urticaria while participating in Stage I of this trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- to obtain steady-state pharmacokinetics of TMC125 b.i.d in treatment-experienced HIV-1 infected children; - to obtain dose recommendations of TMC125 per body weight in treatment-experienced HIV-1 infected children ≥ 6 years old and weighing ≥ 20 kg. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability, obtain dose recommendations per body weight |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
assess pharmacokinetics, safety, tolerability in children |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |