Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Subjects Undergoing Procedure-Type Sedation

The objective of this study is to evaluate the safety of dexmedetomidine in a pediatric population requiring non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) for elective diagnostic or therapeutic procedures, expected to take more than 30 minutes.

This study was designed to evaluate the safety of a continuous infusion of dexmedetomidine (1 mcg/kg loading dose with 0.6 mcg/kg/hr initial maintenance dose and titrated between 0.2-1.0 mcg/kg/hr) administered to subjects requiring non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) for elective diagnostic or therapeutic procedures that are expected to take more than 30 minutes.

Eligibility Criteria:
Inclusion Criteria:

1. Subject is ≥28 weeks gestational age and \<17 years of age.

   - Preterm subjects ≥28 weeks through \<38 weeks, gestational age; (Note: Gestational age will be calculated as the time elapsed between the first day of the last menstrual period to the day of enrollment. If pregnancy was achieved using assisted reproductive technology, gestational age will be calculated by adding 2 weeks to the gestational age as calculated above.)
2. Subject is American Society of Anesthesiologists (ASA) Physical Status I, II or III.
3. Subject requires non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) in an operating or procedure room with an an intensivist, anesthesiologist or dental anesthesiologist in attendance.
4. Scheduled for an elective procedure that falls into one of the following three populations:

   * Non-invasive diagnostic/therapeutic procedures (NIDTP): including ultrasound (US), computed tomography (CT) scans, magnetic resonance imaging (MRI), cardiac catheterization, transthoracic echocardiogram (TTE);
   * Minimally invasive diagnostic/therapeutic procedures (MIDTP): including minimally invasive procedures performed under US or CT guidance (e.g. US or CT-guided solid organ biopsy), and routine myocardial biopsies in cardiac transplant recipients;
   * Surgical procedures: including small surgical procedures (e.g. excisions, biopsies) and dental procedures (e.g. extractions, pulpectomy, pediatric rehabilitation dental procedures, filings and crowns).
5. Duration of the procedure is expected to take at least 30 minutes to complete.
6. 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 and is practicing one of the following methods of birth control: oral or parenteral contraceptives, double-barrier method, vasectomized partner, or abstinence from sexual intercourse.
7. Subject's parent(s) or legally acceptable representative(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:

1. Subjects weight at the time of screening is less than 1000 g.
2. Subject has received general anesthesia within 7 days prior to study drug administration.
3. Subject has participated in an experimental/investigational drug study within 30 days prior to study drug administration.
4. Subject has been exposed to dexmedetomidine within 48 hours prior to study drug administration.
5. Subject that has been previously enrolled in this study (DEX-10-16).
6. Subject requires endotracheal intubation or laryngeal mask airway (LMA).
7. Subject is with neurological conditions that in the opinion of the Investigator will preclude reliable assessment of sedation scoring. Examples include, but are not limited to the following: cerebral palsy, autism, severe mental retardation, etc.
8. Subject has central nervous system (CNS) disease with an anticipated potential for increased intracranial pressure, an uncontrolled seizure disorder and/or known psychiatric illness that could confound a normal response to sedative treatment.
9. Subject requires epidural or spinal anesthesia.
10. Subject has received treatment with an alpha-2 agonist or antagonist within 14 days prior to study drug administration.
11. Subject has a known allergy to dexmedetomidine, midazolam or fentanyl.
12. Subject is requiring cardiac catheterization for the purpose of conducting an electrophysiology (EP) evaluation or percutaneous intervention (i.e. angioplasty).
13. Subject for whom opiates, benzodiazepines, dexmedetomidine or other alpha-2 agonists are contraindicated.
14. Subject has received an IV opioid within one hour, or oral/intramuscular (PO/IM) opioid within four hours, prior to the start of study drug administration.
15. Subject has received any pre-induction medication (ie, ketamine, chloral hydrate, benzodiazepines) within 4 hours prior to the start of study drug administration.
16. Subject has acute myocardial infarction recently diagnosed by confirmatory laboratory findings within 6 weeks of screening.
17. Subject has moderate to severe sleep apnea syndrome.
18. Subject has oxygen saturation (SpO2) ≤90% at screening or baseline, except for patients with known cyanotic heart disease undergoing cardiac catheterization.
19. Subject has bradycardia immediately before dosing, according to respective age group.

    * ≥28 weeks to \<1 month: Heart Rate (HR) \<120 beats per minute (bpm)
    * 1 month to \<3 months: HR \<100 bpm
    * 3 months to \<6 months: HR \<90 bpm
    * 6 months to \<1 year: HR \<80 bpm
    * 1 year to \<2 years: HR \<70 bpm
    * 2 years to \<6 years: HR \<60 bpm
    * 6 years to \<12 years: HR \<55 bpm
    * 12 years to 17 years: HR \<50 bpm;

    Note: Subject can be reassessed after 5 minutes
20. Subject has hypotension immediately before dosing, according to respective age group.

    * ≥28 weeks to \<1 month: \<60 mmHg (systolic blood pressure \[SBP\])
    * 1 month to \<12 months: \<70 mmHg (SBP)
    * 1 year to \<10 years: \<70 + (2 X age in years) mmHg (SBP)
    * 10 years to 17 years: \<90 mmHg (SBP);

    Note: Subject can be reassessed after 5 minutes
21. Subject has a presence of second-degree or third-degree heart block at screening or baseline. The presence of a temporary or permanent pacemaker will waive this exclusion criterion.
22. Subject has acute febrile illness, with a temperature (core or tympanic) ≥38.0°C.
23. Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.