Pharmacokinetic Study of Dexmedetomidine After Intra-Nasal and Buccal Dosing in Children

Heart Diseases Clinical Trial

— DexPK  

Official title:

Pharmacokinetic Study of Dexmedetomidine After Intra-Nasal and Buccal Dosing in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03668951
• Other study ID #: 2018-3034
• Status: Completed
• Phase: Phase 1
• Start date: August 20, 2018
• Est. completion date: May 3, 2022

Study information

• Verified date: February 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is a continuation of a previous DEX PK study. It is examining the absorption of Dexmedetomidine (DEX) in the blood when given orally and as a nasal spray. This study will help us determine the best dosing amount for children undergoing sedation or anesthesia with DEX.

Description:

The study will be a prospective study of plasma concentrations after intranasal or buccal DEX to determine the early pharmacokinetics and bioavailability of a single dose via nasal or oral administration.

Dexmedetomidine sedation is commonly used at Cincinnati Children's Medical Center and other pediatric institutions. This compound is typically delivered intravenously or intranasally for sedation in children with or without congenital heart disease. Intranasal DEX is very effective for sedation although it has significant variability in the onset and peak effect. Patient care will be improved if factors that determine this variability can be determined. Investigators will determine the important clinical variables of peak plasma DEX concentration (Tmax and Cmax) of intranasal and buccal DEX in children.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 3, 2022
• Est. primary completion date: May 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 48 Months

Eligibility

Inclusion Criteria:

• Children aged 6 - 48 months (inclusive) scheduled to receive anesthesia for elective cardiac surgery

• The subject must be a candidate to receive Dex as determined by one of the study cardiac anesthesiologists

• The attending cardiac anesthesiologists for the case and the Chief of Anesthesia Cardiac Anesthesia will concur with or veto this decision

• The subjects legally authorized representative has given written informed consent to participate in the study

Exclusion Criteria:

• Post-natal age less than 6 months

• The subject is allergic to or has had a contraindication to Dex

• Severely depressed ventricular function on preoperative echocardiogram

• The subject has a high risk of cardiac conduction system disease in the judgement of the attending anesthesiologist or cardiologist

• The subject has a hemodynamically significant aortic coarctation or other left heart outflow obstruction

• The subject has received digoxin, beta-adrenergic antagonist, or calcium channel antagonist on the day of surgery

• The subject has received Dex within 1 week of the study date

• Patients who are to receive intranasal Dex are excluded if they have nasal/respiratory symptoms, which in the opinion of the study anesthesiologist, may affect intranasal drug absorption

Related Conditions & MeSH terms

• Heart Diseases

Intervention

Drug:
• Dexmedetomidine buccal
DEX 2 mcg/kg buccal
• Dexmedetomidine Intranasal
DEX 3 mcg/kg intranasal
• Dexmedetomidine Intranasal
DEX 4 mcg/kg intranasal

Locations

Country	Name	City	State
United States	Joanna Paquin	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum blood concentration level of Dex - Cmax	Dex concentration will be measured in the blood to determine the time point with the maximum concentration (Cmax).	Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .
Primary	The amount of time that Dex is present at the maximum concentration - Tmax	Dex concentration will be measured in the blood to determine the time point with the maximum concentration and how long that maximum concentration lasts.	Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .
Secondary	Area under the curve for Dex concentration levels	Dex concentration will be measured in the blood samples.	Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .
Secondary	Bioavailability of intranasal Dex relative to intravenous Dex for distribution - plasma concentration	Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators will be measuring for approximately one half-life of Dex. This will allow us to estimate the important clinical parameter of relative bioavailability of intranasal vs intravenous Dex.	Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .
Secondary	Bioavailability of IN Dex relative to intravenous Dex for elimination - plasma concentration.	Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators will be measuring for approximately one half-life of Dex. This will allow us to estimate the important clinical parameter of relative bioavailability of intranasal vs intravenous Dex.	Blood samples will be drawn at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after Dex has been .
Secondary	Adverse events associated with Dex administration	Heart rate will be recorded by clinical staff prior to the procedure and continuously during the procedure. The heart rate during the time of study blood collection will be compared to the baseline vitals to determine is any adverse events occurred.	Participants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.
Secondary	Systolic and diastolic blood pressure with Dex administration	Systolic and diastolic blood pressure will be recorded by clinical staff prior to the procedure and continuously during the procedure. The systolic and diastolic blood pressure during the time of study blood collection will be compared to the baseline blood pressure to determine is any adverse events occurred.	Participants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.