Study of DA-9501 In Pediatric Subjects In The Intensive Care Unit

Phase 3, Multi-center, Single-arm, Open-label Study Evaluating The Efficacy, Safety, And Pharmacokinetics Of Da-9501 (Dexmedetomidine Hydrochloride) In Pediatric Subjects In The Intensive Care Unit

To evaluate the efficacy, safety, and pharmacokinetics of dexmedetomidine given as continuous IV infusion in pediatric subjects [≥ 45 weeks CGA (corrected gestational age) to <17 years old] requiring sedation under intensive care unit

Inclusion Criteria:

1. Subjects whose consent is obtained in writing prior to the clinical trial from a guardian after a full explanation. For subjects over 7 years old, it is desirable that an informed assent is also obtained from the pediatric subject him/herself when possible.
2. Subjects aged ≥45 weeks CGA to <17 years old at time of consent. No restriction on sex of subject.
3. [Elective surgical cases] Subjects classified as American Society of Anesthesiologists (ASA) (ASA physical status classification) Class I to III by preoperative diagnosis.
4. [Elective surgical cases] Subjects who require at least 6 hours of respiratory management with intubation under intensive care from immediately after surgery and are anticipated to require sedation.
5. [Medical ICU cases] Subjects who require at least 24 hours of respiratory management with intubation under intensive care and are anticipated to require sedation. For medical ICU cases, sedatives used prior to treatment with the investigational product should be discontinued before the start of treatment with the investigational product.
6. If a subject is a female of childbearing potential, she should not be pregnant or possibly pregnant, or lactating.

Exclusion Criteria:

1. Subjects who are judged by investigator or sub-investigator to have a neurological disease that will make sedation assessment difficult, such as:

   • Subjects with brain damage which is expected to increase intracranial pressure due to trauma or central nervous system disease
   • Subjects with cerebral palsy, autism, severe mental retardation, etc.
   • Subjects with paralysis due to continuous administration of a muscle relaxant or due to a spinal injury of class T5 or higher.

2. Subjects with 2nd or 3rd degree heart block during the tests at the screening visit (excluding subjects using a pacemaker).

3. Subjects with any of the following low blood pressure levels during the tests at the screening visit:

   • Age ≥ 45 weeks CGA to < 1 year old: Systolic Blood Pressure (SBP) <70 mmHg
   • Age ≥ 1 year old to < 10 years old: SBP < 70 + (2 x age in years) mmHg
   • Age ≥ 10 years old to < 17 years old: SBP < 90 mmHg

4. Subject of bradycardia (≤10th centile of heart rate for healthy children) during the physical examination at screening period.

5. Subjects with ALT ≥100 U/L during the laboratory tests at the screening visit.

6. Subjects in whom dexmedetomidine or other alfa 2 receptor agonists, alfa 2 receptor antagonists and drug that may be used in this study are contraindicated.

7. Subjects who may need a sedative or analgesic (including narcotics) other than dexmedetomidine, midazolam or fentanyl during treatment with the investigational product.

8. Subjects who have acute febrile illness [with a temperature (core or tympanic) ≥ 38.0°Centigrade] at the screening visit.

9. Subjects who received other investigational product within 30 days before baseline or subjects who will participate in other study that uses an investigational product during the study period.

10. Subjects who received dexmedetomidine within 48 hours before baseline.

11. Subjects who, in the opinion of the investigator or sub-investigator, may be at increased risk to the subject due to the conduct of the study or may have a disease or factor which will probably preclude the obtainment of sufficient study data.

12. Subjects for whom, in the opinion of the investigator or sub-investigator, risks involved with administration of dexmedetomidine outweigh its benefits (e.g., >2 doses of vasopressor due to cardiogenic shock).

13. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Sponsor's employees directly involved in the conduct of the study.