Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children

NCT02836431 | Completed Phase 1 DMC

• 1 other identifier: 2015-5966
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is examining the absorption of the sedative dexmedetomidine (DEX) in the blood when given by nasal spray. The study will help us determine the best dosing amount for children undergoing sedation or anesthesia with DEX.

Conditions

Heart Disease

Keywords

Pediatric; Sedation; Dexmedetomidine

Outcome Measures

Primary Outcomes (5)

• 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 obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.

  Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours

• The amount of time that a 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 (Tmax). Blood samples will be obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.

  Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours

• Area under the curve for DEX concentration levels

  DEX concentration will be measured in the blood samples. Blood samples will be obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.

  Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours

• 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 are limited in sampling duration to the onset time for cardiopulmonary bypass in this patient population (approximately two hours), investigators will be measuring distribution for approximately one half-life of DEX. This will allow us to estimate the important clinical parameter of relative 0-2h bioavailability of intranasal vs intravenous DEX.

  Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours

• Bioavailability of intranasal DEX relative to intravenous DEX for elimination - plasma concentration

  Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators are limited in sampling duration to the onset time for cardiopulmonary bypass in this patient population (approximately two hours), investigators will be measuring elimination for approximately one half-life of DEX. This will allow us to estimate the important clinical parameter of relative 0-2h bioavailability of intranasal vs intravenous DEX.

  Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours

Secondary Outcomes (1)

• Adverse events associated with DEX administration

  Participants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.

Study Arms (3)

DEX 1 mcg/kg Intranasal

EXPERIMENTAL

Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.

Drug: Dexmedetomidine 1mcg/kg Intranasal

DEX 2 mcg/kg Intranasal

EXPERIMENTAL

Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.

Drug: Dexmedetomidine 2mcg/kg Intranasal

DEX 1 mcg/kg Intravenous

EXPERIMENTAL

Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.

Drug: Dexmedetomidine 1mcg Intravenous

Interventions

Dexmedetomidine 1mcg/kg Intranasal DRUG

DEX 1 mcg/kg Intranasal

DEX 1 mcg/kg Intranasal

Dexmedetomidine 2mcg/kg Intranasal DRUG

DEX 2 mcg/kg Intranasal

DEX 2 mcg/kg Intranasal

Dexmedetomidine 1mcg Intravenous DRUG

DEX 1 mcg/kg Intravenously

DEX 1 mcg/kg Intravenous

Eligibility Criteria

• Age: 6 Months - 48 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 6 - 48 months (inclusive) scheduled to receive anesthesia for elective cardiac surgery.
• The subject must be a candidate to receive DEX. A physician member of the Division of Cardiac Anesthesiology, not involved in the study, will make this decision.
• The subject's legally authorized representative has given written informed consent to participate in the study.

You may not qualify if:

• Post-natal age (PNA) \< 6 months
• The subject is allergic to or has a contraindication to DEX
• Severely depressed ventricular function (ejection fraction 30% or less) on preoperative echocardiogram
• The subject has high risk cardiac conduction system disease at the discretion of the attending anesthesiologist or cardiologist.
• The subject has a hemodynamically significant coarctation or other left heart outflow obstruction
• The subject has received digoxin, beta-adrenergic antagonist, or calcium-channel antagonist on the day of the study
• The subject has received DEX within 1 week of the study date (information obtained from: parent or Medical record)
• Subject have nasal/respiratory symptoms which in the opinion of the Principal investigator, may affect intranasal drug absorption.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Heart Diseases

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jeff Miller, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: July 19, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2018
• Last Updated: July 30, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)