E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
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 study the pharmacokinetics and pharmacodynamics of paracetamol intravenously in preterm infants with a gestational age of less than 32 weeks:
• Time – paracetamol serum concentration profile
• Covariate effects on pharmacokinetics.
• Determine estimates of clearance
• Volume of distribution
|
|
E.2.2 | Secondary objectives of the trial |
To study the safety of paracetamol intravenously as measured by LD, AST, ALT
To study the effect op paracetamol on painscores
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Gestational age less than 32 weeks
• Analgesia indicated as per pain protocol
• Indwelling arterial catheter available
• Informed consent
|
|
E.4 | Principal exclusion criteria |
• Co-medication: analgesia, sedatives, muscle relaxants, phenobarbital
• Asphyxiated patients
• Signs of liver failure prior to inclusion |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Paracetamol serum levels, |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
½,1, 3, 6 hours after administration of the first doses, and an additional sample 6 hours after administration of the last dose. |
|
E.5.2 | Secondary end point(s) |
1. Serum values of unconjugated bilirubin, AST and ALT
2. Glutathion, paracetamol urine levels, paracetamol-sulphate and paracetamol-glucuronide
3. Painscores (PIPP) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. before the first administration and 1 hour after administration of the last study dose.
2. at 6 and 30 hours after administration of the first dose.
3. every 8 hours for the duration of treatment.
|
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | No |
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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.1.7 | Other | No |
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
| 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
|
When data from 15 subjects have been obtained |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |