Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects - Full Text View

Sponsored by:	Hospira, Inc.
Information provided by:	Hospira, Inc.
ClinicalTrials.gov Identifier:	NCT00652028

Purpose

The objective of this study is to characterize the pharmacokinetic and pharmacodynamic profile of dexmedetomidine administered as an intravenous bolus followed by a continuous intravenous infusion in pediatric subjects ages greater than or equal to 2 through < 17 years old.

Condition	Intervention	Phase
Intubated and Mechanically Ventilated Pediatric Subjects	Drug: midazolam; fentanyl	Phase II

MedlinePlus related topics: Children's Health

Drug Information available for: Fentanyl Citrate Fentanyl Midazolam Midazolam hydrochloride Midazolam maleate Dexmedetomidine Dexmedetomidine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title:	A Phase II, Open-Label, Multicenter, Escalating Dose, Study to Determine Pharmacokinetic and Pharmacodynamic Profile of Dexmedetomidine in Pediatric Subjects Ages > 2 Through < 17 Years Old

Further study details as provided by Hospira, Inc.:

Primary Outcome Measures:

Assessment of pharmacokinetics and pharmacodynamics of dexmedetomidine [ Time Frame: Over 24 hour period ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	56
Study Start Date:	August 2008
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 Dose level 1	Drug: midazolam; fentanyl Midazolam for sedation according to label; fentanyl for pain according to the label
Group 2 Dose level 2	Drug: midazolam; fentanyl Midazolam for sedation according to label; fentanyl for pain according to the label
Group 3 Dose level 3	Drug: midazolam; fentanyl Midazolam for sedation according to label; fentanyl for pain according to the label
Group 4 Dose level 4	Drug: midazolam; fentanyl Midazolam for sedation according to label; fentanyl for pain according to the label

Detailed Description:

This is a phase II, open-label, multicenter, escalating dose study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects. The study population consists of initially intubated and mechanically ventilated pediatric subjects, ages > or equal to 2 through < 17 years old, that require sedation in an intensive care setting for a minimum of 6 hours. Subjects will be divided into two groups based on age: Group I will consist of subjects ages > or equal to 2 through < 6 years old and Group II subjects age > or equal to 6 through < 17 years old. Within each group there will be four escalating dosing levels. Both groups can enroll simultaneously; however within each group, the next dose level cannot begin to enroll until all subjects have completed the previous dose level and the Data Safety Monitoring Board (DSMB) has approved enrollment to the next level. The level of sedation will be assessed using the Ramsay Sedation Scale (RSS). Based on these scores, and clinical judgment, additional sedation with midazolam will be administered according to the label. Pain will be assessed using the Faces, Legs, Arms, Cry & Consolability (FLACC) scale. Venous blood samples for pharmacokinetic analysis will be obtained at designated times. The pharmacodynamic and safety measures that will be monitored and the pharmacodynamic impact of dexmedetomidine on tracheal extubation will also be explored if subject is extubated within 24 hours.

Eligibility

Ages Eligible for Study:	2 Years to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require a minimum of 6 hours of continuous intravenous sedation.
Age: subjects must fit into one of the following age ranges at screening:
- > or equal to 2 years old through < 6 years old
- > or equal to 6 years old through < 17 years old
If female, subject is non-lactating and is either:
1. Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.
2. Of childbearing potential but is not pregnant at time of baseline.
Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board. Assent will be obtained where age-appropriate and according to state regulations.

Exclusion Criteria:

Pediatric subjects with neurological conditions that prohibit an evaluation of sedation
Weight < 10 kg.
Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
Hepatic impairment SGPT/ALT >100 U/L
Hypotension based on repeat assessments
Pre-existing bradycardia
Acute thermal burns involving more than 15 percent total body surface area.
Subjects who have a known allergy to dexmedetomidine, MDZ or fentanyl.
Subjects with a life expectancy that is < 72 hours.
Subjects that are expected to have hemodialysis (continuous hemofiltration) or peritoneal dialysis within 48 hours.
Subjects who have been treated with α-2 agonists/antagonists within two weeks.
Subjects with a spinal cord injury above T5.
Subjects who have received another investigational drug within the past 30 days.
Subjects on nicotine replacement therapy.
Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652028

Contacts

Contact: Katie Weber	224-212-4633	katie.weber@hospira.com
Contact: Valerie Bell	224-212-4726	valerie.bell@hospira.com

Locations

United States, New York
Children's Hospital of Buffalo	Recruiting
Buffalo, New York, United States, 14222
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Guatemala
Unidad Cirugia Cardiovascular de Guatemala	Recruiting
Guatemala City, Guatemala

Sponsors and Collaborators

Hospira, Inc.

More Information

Responsible Party:	Hospira, Inc. ( Paula Bokesch, MD )
Study ID Numbers:	DEX-08-01
Study First Received:	April 1, 2008
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00652028
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hospira, Inc.:

Pharmacokinetics
Pharmacodynamics
Escalating dose
Dexmedotimidine

Intubated
Mechanically ventilated
Pediatrics

Study placed in the following topic categories:

Fentanyl
Dexmedetomidine
Midazolam

Additional relevant MeSH terms:

Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
Physiological Effects of Drugs
Psychotropic Drugs
Anesthetics
Adrenergic Agonists
Sensory System Agents
Therapeutic Uses
Hypnotics and Sedatives
Analgesics
Analgesics, Opioid

Anesthetics, Intravenous
Tranquilizing Agents
Adrenergic alpha-Agonists
Central Nervous System Depressants
Narcotics
Pharmacologic Actions
Adjuvants, Anesthesia
Anesthetics, General
Analgesics, Non-Narcotic
GABA Agents
Anti-Anxiety Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009