E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sick newborn infants in need of intensive care. |
|
E.1.1.1 | Medical condition in easily understood language |
Sick newborn infants in need of intensive care. |
|
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 |
• study the PK of dexmedetomidine using NONMEM® (Non-linear Mixed
Effect Modelling) population-based PK modelling (62) and
• assess the effects of the drug on brain function (PD) and relate the
effects to drug concentration (PK/PD). |
|
E.2.2 | Secondary objectives of the trial |
• the physiological parameters (including NIRS),
• 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). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Newborn infants
- born 34+0 gw with a need for dexmedetomidine for analgesic
and/or sedative treatment after postnatal surgical correction of
congenital malformations and who will be cared for in the
PICU/postoperative unit and in a some few cases in the NICU, or
- with a corresponding age of 37 gw, who are in need for
dexmedetomidine according to clinical judgment (scoring with pain
assessment scales; ALPS-Neo and Comfort-Neo) and cared for in the
NICU.
• Existing arterial or venous cannulas/catheters for repeated nontraumatic
blood sampling
• Informed and written parental consent obtained before study start. |
|
E.4 | Principal exclusion criteria |
•Infant older than age corresponding to gw 46+0
•Previous treatment with the dexmedetomidine or clonidine within 72 hours (only for postoperative infants).
•Congenital cardiac malformations requiring surgery on extracorporeal circulation and treatment with hypothermia.
•Ongoing renal replacement treatment
•Any serious medical condition or ethical issues that could, in the investigators opinion, interfere with the study procedures.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Pharmacokinetics (PK) of dexmedetomidine
2. Change in hemodynamic response in relation to PK (PK/PD)
3. Change in neurophysiology response in relation to PK (PK/PD) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From 30 min before start of study medication until 24 hours after stop of
study medicaton. |
|
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 PDs.
•Pain response as measured by pain assessment score ALPS-Neo and
Comfort Neo in relation to GSR.
•Procedural pain response, as scored by PIPP-R, to a standardized pain
provocation.
•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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From 30 min before start of study medication until 24 hours after stop of
study medicaton.
Procedural pain response and change in s-kortisol is only measured once
during the study. |
|
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 | Yes |
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) | 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 | 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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |