Clinical trial NCT02757625: Study of DA-9501 In Pediatric Subjects In The Intensive Care Unit
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ICU Sedation
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Maruishi Pharmaceutical
First posted: 2016-05-02
Enrollment: 63
Sex: ALL
Minimum age (years): 45
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Did Not Require a Rescue Sedative Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
Secondary outcomes:
measure: Percentage of Participants Who Did Not Require Administration of a Rescue Analgesic Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Total Amount of Rescue Sedative Administered Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Body Weight Adjusted Total Amount (Per Kg) of Rescue Sedative Taken Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Total Amount of Rescue Analgesic Taken Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Body Weight Adjusted Total Amount of Rescue Analgesic Taken Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Duration of Maintenance of Target Sedation Level Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Percentage of Maintenance Duration of Target Sedation Level Within 24 Hours of Dosing of Study Drug
timeFrame: From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
measure: Percentage of Participants Who Did Not Use a Rescue Sedative After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Percentage of Participants Who Did Not Require Dosing of a Rescue Analgesic After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Total Amount of Rescue Sedative Taken After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Body Weight Adjusted Total Amount of Rescue Sedative Taken After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Total Amount of Rescue Analgesic Taken After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Body Weight Adjusted Total Amount of Rescue Analgesic Taken After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Duration of Maintenance of Target Sedation Level After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Percentage of Maintenance Duration of Target Sedation Level After 24 Hours of Dosing of Study Drug Till End of Mechanical Ventilation
timeFrame: After 24 hours of study drug dosing till end of mechanical ventilation (up to 28 days)
measure: Duration of Maintenance of Target Sedation Level After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Percentage of Maintenance Duration of Target Sedation Level After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Total Amount of Rescue Sedative Taken After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Body Weight Adjusted Total Amount of Rescue Sedative Taken After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Total Amount of Rescue Analgesic Taken After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Body Weight Adjusted Total Amount of Rescue Analgesic Taken After Extubation
timeFrame: From extubation till end of treatment (6 hours after start of study drug dosing up to 28 days)
measure: Median Time to Conclusion of Mechanical Ventilation
timeFrame: Baseline (start of study drug dosing) until end of mechanical ventilation (up to 28 days)
Other outcomes:
measure: Number of Participants With Treatment- Emergent Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Baseline up to 28 days after end of study drug dosing (up to 56 days)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to 28 days after end of study drug dosing (Day 56)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to 28 days after end of study drug dosing (Day 56)
measure: Total Input/Output Fluid Volume
timeFrame: Baseline up to 28 days after end of study drug dosing (Day 56)
measure: Incidence of Potential Withdrawal Symptoms
timeFrame: Baseline up to 28 days after end of study drug dosing (Day 56)
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to 28 days after end of study drug dosing (Day 56)
Locations:
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Hyogo Prefectural Kobe Children's Hospital
state: Hyogo
city: Zentsuji
country: Japan
facility: Shikoku Medical Center for Children and Adults
state: Kagawa
city: Izumi
country: Japan
facility: Osaka Women's and Children's Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Fuchu
country: Japan
facility: Tokyo Metropolitan Children's Medical Center
state: Tokyo
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Children's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Takeuchi M, Nemoto S, Suzuki Y, Takahashi N, Takenaka N, Takata A, Kobayashi M. Age-Specific Dose Regimens of Dexmedetomidine for Pediatric Patients in Intensive Care Following Elective Surgery: A Phase 3, Multicenter, Open-Label Clinical Trial in Japan. Pediatr Crit Care Med. 2021 Nov 1;22(11):e546-e557. doi: 10.1097/PCC.0000000000002730.