E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sick preterm infants undergoing neonatal intensive care. |
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E.1.1.1 | Medical condition in easily understood language |
Sick preterm infants undergoing neonatal intensive care. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 |
The specific aims of this Project are to
•study the PK of clonidine in preterm infants using NONMEM® (Nonlinear
Mixed Effect Modelling) population based PK modelling.
• assess the effects of the drug on brain function (PD) in these infants
and relate the effects to drug concentration (PK/PD). |
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E.2.2 | Secondary objectives of the trial |
• assess the effects of the drug concentration (PK/PD) on to the physiological parameters (including NIRS) and relate the effects to drug concentration (PK/PD).
• assess the pain response (pain assessment scales and GSR) in these infants and relate the effects to drug concentration (PK/PD).
• develop a Swedish version of COMFORT-neo that is valid and culturally adapted
• validate ALPS-Neo against behavioural and biomedical pain markers (Comfort-neo, GSR and S-cortisol)
and determine whether a specific pharmacogenetic (PG) profile explains the PK and PD phenotypes of this drugs in newborn infants (PK/PD/PG).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication according to clinical judgment (scoring with pain assessment scales; ALPS-Neo and Comfort-Neo)
• Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
• Informed and written parental consent
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E.4 | Principal exclusion criteria |
• Hemodynamic instability (same as in clinical routine).
• Cardiac malformations in need for postnatal surgery.
• Any serious medical condition or ethical issues that could, in the Investigators opinion, interfere with the study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in drug concentration (metabolism) relate to XXX
• Effect of other medicines on clerance (including but not limited to
phenobarbitone, midazolam, thiopentone).
• Change in neurophysiology response in relation to PK |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
pre and until 72 h of treatment. |
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E.5.2 | Secondary end point(s) |
•Change in/association between physiological parameters (heart rate (HR), mean arterial blood pressure (MABP, recorded invasively and, peripheral oxygen saturation (SpO2)) in relation to PK and other PD
parameters.
•Change in/association between pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) and GSR, in relation to PK and other PD.
•Pain response as measured by pain assessment score ALPS-Neo and Comfort Neo in relation to GSR (=galvanic skin respons)
•Change in S-Cortisol in relation to PK and PD and pain response at a standardized pain procedure performed at a stage of stability after 6 hours of unchanged medication,
•How PK/PD phenotypes depend on pharmacogenetic (PG) profiles. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
pre and until 72 h of treatment. |
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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 | 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 | 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) | 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) | Yes |
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 | 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 | 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
| 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 | 2 |
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
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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 |