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

NCT03417999 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 17-014084
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The main objectives of the study are to determine peak plasma drug concentration levels and corresponding time of dexmedetomidine following intranasal administration in children age ≥1 mo to ≤ 6 yr with congenital heart disease undergoing an elective diagnostic or interventional cardiac catheterization procedure.

Conditions

Dexmedetomidine; Congenital Heart Disease

Keywords

Intranasal; Pharmacokinetic; Pediatric

Outcome Measures

Primary Outcomes (4)

• Number of Samples Obtained Per Subject

  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.

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

• Time of Peak Drug Concentration Level of Dexmedetomidine

  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. The time of peak drug concentration will be determined based on this data.

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

• Serum Drug Concentration Levels of Dexmedetomidine

  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.

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

• Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL

  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.

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

Study Arms (2)

Cohort 1

EXPERIMENTAL

Cohort 1A: * Dexmedetomidine 2 μg/kg * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo * 7 subjects age ≥1 mo and ≤2 yo Cohort 1B: * Dexmedetomidine 2 μg/kg * Under sedation with a natural airway * 7 subjects age \>2 yo and ≤ 6 yo * 7 subjects age ≥1 mo and ≤2 yo

Drug: Dexmedetomidine

Cohort 2

EXPERIMENTAL

* Dexmedetomidine 4 μg/kg * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

Dose-escalation of atomized intranasal dexmedetomidine

Also known as: Precedex

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 1 Month - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female subjects age ≥1 mo to ≤6 yo.
• Subjects must have congenital heart disease.
• American Society of Anesthesiology (ASA) Physical Status 1-3.
• Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours.
• Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours.
• Subjects must have reliable intravascular access from which to draw blood samples.

You may not qualify if:

• History of allergic reaction or sensitivity to dexmedetomidine.
• Nasal pathology preventing the administration of drug.
• Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme.
• Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence.
• Bradycardia, defined by age, upon arrival in the preoperative care area.
• Hepatic dysfunction defined as a history of hepatic dysfunction AND an Alanine Aminotransferase (ALT) value greater than 2 times normal in the 6 months prior to study drug administration.
• The subject has received dexmedetomidine or clonidine within 1 week of the study date.
• BMI \>30.
• Patients previously enrolled in this study.
• Any investigational drug use within 30 days prior to enrollment.
• Wards will not be eligible.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19106, United States

Location

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

1. Unable to enroll subjects in Cohort 1B to determine if DEX PK is different in patients spontaneously ventilating with a natural airway versus mechanically ventilated via oral endotracheal tube. 2. Unable to sample long enough to determine elimination phase of IN DEX. 3. Small sample size and heterogenous population limit interpretation of results. 4. COVID delayed enrollment and loss of research personnel. 5. PI left institution prior to completion of study and so study was terminated.

Results Point of Contact

• Title: Dr. Kelly Grogan
• Organization: Children's Hospital of Philadelphia

grogank@chop.edu

410-279-6994

Study Officials

• Kelly L Grogan, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Anesthesia and Critical Care Medicine, Principal Investigator

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 31, 2018
• Study Start: June 14, 2018
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: March 22, 2024
• Results First Posted: March 22, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)