Trial Outcomes & Findings for Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease (NCT NCT03417999)

Last Updated: 2024-03-22

Results Overview

Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. This is the number of samples obtained per subject.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration

Results posted on

2024-03-22

Participant Flow

Prospective open-label inter-subject cohort dose escalation PK and PD study performed at a since center in a pediatric cardiac catheterization laboratory. Study was approved by IRB on 4/23/18 and the FDA initiation date was 11/29/17. Subjects were enrolled from 06/14/18 through 8/23/21. All study related activities were completed on 10/13/21.

Some of our subjects were scheduled for a cardiac MRI prior to their heart catheterization. If the MRI answered the clinical question, the heart catheterization was not performed and therefore study drug was not administered.

Participant milestones

Participant milestones
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Overall Study STARTED	10	5	13
Overall Study Evaluable Subjects	7	3	6
Overall Study COMPLETED	7	5	9
Overall Study NOT COMPLETED	3	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Overall Study Withdrawal by Subject	1	0
Overall Study Procedure cancelled; subject did not receive study drug	2	2
Overall Study Met exclusion criteria after obtaining consent	0	1
Overall Study Inadequate study staff available to process samples	0	1

Baseline Characteristics

Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=10 Participants Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=5 Participants Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=13 Participants Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo	Total n=28 Participants Total of all reporting groups
Age, Continuous	44.5 months n=5 Participants	14 months n=7 Participants	40 months n=5 Participants	38.5 months n=4 Participants
Age, Customized >2 yo and ≤ 6 yo	10 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants	23 Participants n=4 Participants
Age, Customized ≥1 mo and ≤2 yo	0 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White or Caucasian	7 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants	28 participants n=4 Participants
Weight	15.2 kilograms n=5 Participants	8.8 kilograms n=7 Participants	16.1 kilograms n=5 Participants	14.7 kilograms n=4 Participants
Mixing lesion present	5 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration

Population: Population includes all subjects who received study drug. This included evaluable and non-evaluable subjects.

Outcome measures

Outcome measures
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=7 Participants Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=5 Participants Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=9 Participants Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Number of Samples Obtained Per Subject	10 Samples Interval 9.0 to 10.0	9 Samples Interval 7.0 to 9.0	10 Samples Interval 6.5 to 10.0

PRIMARY outcome

Timeframe: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration

Population: Analysis population includes subjects who received study drug and had at least 90 minutes of sampling time to ensure that Tmax had been achieved. There was one subject in Cohort 1a who had BLQ for all samples obtained for unknown reasons. This subject's data also not be evaluated.

Outcome measures

Outcome measures
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=7 Participants Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=3 Participants Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=6 Participants Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Time of Peak Drug Concentration Level of Dexmedetomidine	91 minutes Interval 44.0 to 120.0	30 minutes Interval 15.0 to 31.0	54 minutes Interval 45.0 to 106.0

PRIMARY outcome

Timeframe: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration

Population: Analysis population includes subjects who received study drug and had at least 90 minutes of sampling time to ensure that Cmax had been achieved. There was one subject in Cohort 1a who had BLQ for all samples obtained for unknown reasons. This subject's data could also not be evaluated.

Following administration of atomized intranasal dexmedetomidine, serum samples will be obtained at the following times post administrations: 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. Peak concentration will be determined based on this data.

Outcome measures

Outcome measures
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=7 Participants Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=3 Participants Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=6 Participants Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Serum Drug Concentration Levels of Dexmedetomidine	413 pg/mL Interval 311.0 to 565.0	570 pg/mL Interval 315.0 to 679.0	1000 pg/mL Interval 978.0 to 1050.0

PRIMARY outcome

Timeframe: Subjects were monitored for 6 hours after the administration of study drug.

Population: Population includes any subject who received study drug

Dose-limiting toxicities (DLT) include bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event possibly, probably, or definitely related to intranasal dexmedetomidine administration that occured after the administration of the intranasal dexmedetomidine and through the completion of PK sampling. Bradycardia, hypotension, or new intraventricular conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team as part of usual clinical care were not considered DLTs but were considered an adverse event. Any events that could not be explained by the intervention that the patient was undergoing were assumed to be related to the study drug.

Outcome measures

Outcome measures
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=7 Participants Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=5 Participants Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=9 Participants Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL	0 Events	2 Events	3 Events

Adverse Events

2 μg/kg; Subjects Age >2 yo and ≤ 6 yo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

2 ug/kg; Subjects Age ≥1 mo and ≤2 yo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

4 μg/kg; Subjects Age >2 yo and ≤ 6 yo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	2 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=7 participants at risk Cohort 1A: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age \>2 yo and ≤ 6 yo	2 ug/kg; Subjects Age ≥1 mo and ≤2 yo n=5 participants at risk Cohort 1a: * Dexmedetomidine 2 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * Subjects age ≥1 mo and ≤2 yo	4 μg/kg; Subjects Age >2 yo and ≤ 6 yo n=9 participants at risk Cohort 2 * Dexmedetomidine 4 μg/kg, atomized intranasal * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo
Cardiac disorders Bradycardia not requiring intervention	14.3% 1/7 • Number of events 1 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	20.0% 1/5 • Number of events 1 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	11.1% 1/9 • Number of events 1 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.
Cardiac disorders Hypotension not requiring intervention	0.00% 0/7 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	20.0% 1/5 • Number of events 1 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	0.00% 0/9 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.
Cardiac disorders New Intraventricular conduction delay	0.00% 0/7 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	0.00% 0/5 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	0.00% 0/9 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.
Cardiac disorders Maximum Plasma Concentration	0.00% 0/7 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	0.00% 0/5 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.	33.3% 3/9 • Number of events 3 • All subjects were monitored for 6 hours after the administration of study drug. Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.

Additional Information

Dr. Kelly Grogan

Children's Hospital of Philadelphia

Phone: 410-279-6994

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place