Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects
Condition: Intubated and Mechanically Ventilated Pediatric Subjects
Intervention: Dexmedetomidine, midazolam; fentanyl
Intervention description: Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
Intervention MeSH terms: Midazolam; Fentanyl; Dexmedetomidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 2 Years
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Pharmacokinetics; Pharmacodynamics; Escalating dose; Dexmedotimidine; Intubated; Mechanically ventilated; Pediatrics

Summary:

      The objective of this study is to characterize the pharmacokinetic and pharmacodynamic
      profile of dexmedetomidine administered as an intravenous loading dose followed by a
      continuous intravenous infusion in pediatric subjects ages ≥2 through <17 years old.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Initially intubated and mechanically ventilated pediatric subjects in an intensive
             care setting anticipated to require a minimum of 6 hours of continuous intravenous
             sedation.

          -  Age: subjects must fit into one of the following age ranges at screening:

               -  ≥2 years old through <6 years old

               -  ≥6 years old through <17 years old

          -  If female, subject is non-lactating and is either:

               1. Not of childbearing potential, defined as pre-menarche, or surgically sterile due
                  to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.

               2. Of childbearing potential but is not pregnant at time of baseline.

          -  Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the
             informed consent document approved by the Institutional Review Board. Assent will be
             obtained where age-appropriate and according to state regulations.

        Exclusion Criteria:

          -  Pediatric subjects with neurological conditions that prohibit an evaluation of
             sedation

               -  Diminished consciousness from increased intracranial pressure.

               -  Extensive brain surgery (surgery requiring intracranial pressure monitor).

               -  Diminished cognitive function per PI's discretion.

               -  Subjects with immobility from neuromuscular disease or continuous infusion of
                  neuromuscular blocking agents.

          -  Weight <10 kg.

          -  Subjects with second degree or third degree heart block unless subject has a pacemaker
             or pacing wires.

          -  Hepatic impairment Serum glutamic pyruvic transaminase/Alanine aminotransferase
             (SGPT/ALT) >100 U/L

          -  Hypotension based on repeat assessments prior to starting study drug:

               -  Age ≥2 years old through ≤12 years old: systolic blood pressure (SBP) <80 mmHg

               -  Age >12 years old through <17 years old: SBP <90 mmHg

          -  Pre-existing bradycardia prior to starting study drug defined as:

               -  Age ≥2 years old through ≤6 years old: ≤70 beats per minute (bpm)

               -  Age >6 years old through ≤12 years old: ≤60 bpm

               -  Age >12 years old through ≤16 years old: ≤50 bpm

          -  Acute thermal burns involving more than 15 percent total body surface area.

          -  Subjects who have a known allergy to dexmedetomidine, midazolam (MDZ) or fentanyl.

          -  Subjects with a life expectancy that is <72 hours.

          -  Subjects that are expected to have hemodialysis (continuous hemofiltration) or
             peritoneal dialysis within 48 hours.

          -  Subjects who have been treated with α-2 agonists/antagonists within two weeks.

          -  Subjects with a spinal cord injury above T5.

          -  Subjects who have received another investigational drug within the past 30 days.

          -  Subjects on nicotine replacement therapy.

          -  Subjects who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of this clinical study.