Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months

A Phase II, Randomized, Open-Label, Single Center, Pharmacokinetic and Pharmacodynamic Study of Dexmedetomidine in Pediatric Subjects Aged 12 Months Through <24 Months

The purpose of this study is to investigate the pharmacokinetic, pharmacodynamic, and safety of dexmedetomidine at 2 different dose levels in pediatric subjects, aged 12 months through <24 months, administered as an intravenous loading dose followed by continuous infusion for a minimum of 6 hours and up to 24 hours in an intensive care setting.

Phase II, randomized, open-label, single-center, study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects across two dose levels (Dose Level 1 consists of a 0.7 mcg/kg loading dose immediately followed by a 0.5 mcg/kg/hr maintenance infusion; Dose Level 2 consists of a 1.0 mcg/kg loading dose immediately followed by a 0.75 mcg/kg/hr maintenance infusion). The study population will consist of intubated and mechanically ventilated pediatric subjects who require sedation in an intensive care setting for a minimum of 6 hours but not to exceed 24 hours. Subjects eligible for enrollment are 12 months to <24 months of age.

Inclusion Criteria:

1. Subject is 12 months to <24 months of age at screening.
2. Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
3. Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
4. The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.

Exclusion Criteria:

1. Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:

   • Diminished consciousness from increased intracranial pressure
   • Extensive brain surgery (surgery requiring intracranial pressure monitor)
   • Diminished cognitive function per Principal Investigator (PI) discretion
   • Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.

2. Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.

3. Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.

4. Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.

5. Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.

6. Subject who have acute thermal burns involving more than 15 percent total body surface area.

7. Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.

8. Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.

9. Subjects with a life expectancy that is <72 hours.

10. Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.

11. Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.

12. Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).

13. Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.

14. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.