E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Initially intubated and mechanically ventilated preterm
neonates ≥ 28 weeks through < 36 weeks gestational age and term neonates born at ≥ 36 weeks through
≤ 44 weeks gestational age in an intensive care setting anticipated to require a minimum of 6 hours of
continuous IV sedation. Weight at the time of enrollment had to be > 1000 g |
|
E.1.1.1 | Medical condition in easily understood language |
initially intubated and mechanically
ventilated male and female neonate subjects, age ≥ 28 weeks to ≤ 44 weeks gestational
age, who require sedation in an IC setting for a minimum of 6 hours |
|
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 |
The objective of this study is to characterize the safety, efficacy and PK of DEX
administered as an IV loading dose followed by a continuous IV infusion in neonates,
ages ≥ 28 weeks through ≤ 44 weeks gestational age |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Initially intubated and mechanically ventilated pediatric subjects in an intensive
care setting anticipated to require a minimum of 6 hours of continuous IV
sedation.
2. The ability to complete all PK sampling blood draws.
NB: The presence of an indwelling venous or arterial catheter for blood sampling;
with an umbilical venous or arterial catheter is preferred but not required.
3. Age: subjects must fit into 1 of the following age ranges at screening:
• Preterm neonates ≥ 28 weeks through < 36 weeks, gestational age; this would
constitute treatment Group I.
• Term neonates born at ≥ 36 weeks through ≤ 44 weeks gestational age; this would
constitute treatment Group II.
Gestational age (in weeks) will be calculated as follows: the time elapsed between
the first day of the last menstrual period and the day of delivery
Weight: subject’s weight at the time of enrollment must be > 1000 g.
5. Subject’s parent(s) or legal guardian(s) has/have voluntarily signed and dated the
informed consent document approved by the Institutional Review Board
(IRB)/Independent Ethics Committee (IEC). |
|
E.4 | Principal exclusion criteria |
1. Neonate subjects with neurological conditions that prohibit an evaluation of
sedation such as:
• Diminished consciousness from increased intracranial pressure.
• The presence of catastrophic brain injury or other severe mental disorders that
would make responses to sedatives unpredictable and/or measurement of the
N-PASS unreliable.
• Subjects with immobility from neuromuscular disease or continuous infusion of
neuromuscular blocking (NMB) agents.
2. Subjects with second degree or third degree heart block unless subject has a
pacemaker or pacing wires are in situ.
3. HR < 120 bpm prior to the initiation of study drug.
4. Exposure to any investigational drug within 30 days prior to study drug
administration.
5. Previous exposure to DEX as part of an investigational study
Maternal history of poly-substance drug abuse, based upon the presence of 1) an
abnormal urine drug screen for cocaine, opiates and/or benzodiazepines; or 2)
Investigator’s judgment.
7. At the discretion of the Investigator, subjects in whom the risk of DEX treatment is
expected to exceed its benefits.
8. Subjects who have a known allergy or contraindication to fentanyl, morphine,
MDZ, DEX, or other α-2 agonists.
9. Requirement for medications other than DEX, MDZ, morphine, or fentanyl for
sedation and pain control.
10. Screening ALT levels > 115 U/L. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for the study was the incidence of subjects requiring any rescue
medication (midazolam [MDZ]) for sedation during DEX infusion.
The primary PK parameters were as follows:
● CL (plasma clearance) and
● CLw (weight adjusted CL |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
the
minimum duration of DEX infusion is 6 hours and the maximum duration of infusion will
not exceed 24 hours |
|
E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints included:
● Incidence of rescue medication use for analgesia during DEX infusion
● (a) The total amount and (b) the weight adjusted total amount (per kg) of rescue medication of
MDZ, morphine, or fentanyl given for sedation and analgesia during DEX infusion
● Change from baseline in vital signs (heart rate [HR], systolic blood pressure [SBP], diastolic
blood pressure [DBP], mean arterial pressure [MAP], respiration rate [RR], and oxygenation
[SpO2]) during DEX infusion
● Time spent with a total Neonatal Pain, Agitation and Sedation Scale (N-PASS) score > 3 and
≤ 3 during DEX infusion
● Time to extubation was explored in DEX-exposed subjects |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
the
minimum duration of DEX infusion is 6 hours and the maximum duration of infusion will
not exceed 24 hours |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | 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 |
Pk, efficacy and safety study in neonates |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |