E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Age-related changes in intestinal drug metabolism in children |
|
E.1.1.1 | Medical condition in easily understood language |
Age-related changes in oral drug absorption in children |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
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 elucidate the developmental pattern of important intestinal drug metabolizing pathways using microdosing in neonates and infants |
|
E.2.2 | Secondary objectives of the trial |
To show the feasibility of microdosing in children for use in mechanistic pharmacology studies and ‘first-in-child’ drug trials To determine the effect of genetic polymorphisms on intestinal metabolism of paracetamol in children
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 0 until 6 years At least 32 weeks of post conceptual age Possess an intravenous or intra-arterial access for blood sampling Need for paracetamol intravenously Parental informed consent |
|
E.4 | Principal exclusion criteria |
Anticipated death in 48 hours Withdrawal of informed consent
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics of the labeled and unlabeled parent compound and metabolites will be determined. Results will be stratified by age and population pharmacokinetics will be used. This will enable us to determine the ontogeny of the intestinal paracetamol metabolism pathways. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time after completion of the last included patient |
|
E.5.2 | Secondary end point(s) |
To show the feasibility of microdosing in children for use in mechanistic pharmacology studies and ‘first-in-child’ drug trials. To study the effect of co-variates on drug disposition. Co-variates: gender, co-medication, laboratory markers (if determined as part of clinical care): inflammation marker (CRP, leucocyte count, IL6, TNF-alpha, PCT, NGAL), DNA (for genes related to paracetamol disposition, e.g. UGT1A6) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time after completion of the last included patient |
|
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 | No |
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 | Yes |
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 | Yes |
E.7.1.3.1 | Other trial type description |
Microdosing study to elucidate the ontogeny of intestinal drugmetabolism pathway of paracetamol |
|
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |