Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age

A Phase II/III, Open-Label, Multicenter, Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Neonates Ages ≥28 Weeks to ≤44 Weeks Gestational Age

The purpose of this study is to investigate the safety, efficacy and pharmacokinetics (PK) of dexmedetomidine (DEX) at 3 different dose levels in infants, ages ≥28 weeks to ≤44 weeks gestational age, administered as a loading dose followed by a continuous infusion for a minimum of 6 hours and up to 24 hours in the neonatal intensive care unit (NICU), cardiac intensive care unit (CICU), or pediatric intensive care unit (PICU).

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.

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.

4. 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).

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. Heart rate <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 Dexmedetomidine (DEX) as part of an investigational study.

6. 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, Midazolam, DEX, or other α-2 agonists.

9. Requirement for medications other than DEX, Midazolam, morphine, or fentanyl for sedation and pain control.

10. Screening alanine aminotransferase (ALT) levels >115 U/L.