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Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospira, Inc.
ClinicalTrials.gov Identifier:
NCT00652028
First received: April 1, 2008
Last updated: September 6, 2011
Last verified: September 2011
  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: Dexmedetomidine, midazolam; fentanyl
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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 ]

Enrollment: 59
Study Start Date: August 2008
Study Completion Date: August 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group 1
Dose level 1
Drug: Dexmedetomidine, midazolam; fentanyl
Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
Group 2
Dose level 2
Drug: Dexmedetomidine, midazolam; fentanyl
Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
Group 3
Dose level 3
Drug: Dexmedetomidine, midazolam; fentanyl
Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
Group 4
Dose level 4
Drug: Dexmedetomidine, midazolam; fentanyl
Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Florida
Variety Children's Hospital/Miami Children's Hospital
Miami, Florida, United States, 33155
United States, Kentucky
University of Louisville/Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, New York
Children's Hospital of Buffalo
Buffalo, New York, United States, 14222
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23219
Guatemala
Unidad Cirugia Cardiovascular de Guatemala
Guatemala City, Guatemala
Sponsors and Collaborators
Hospira, Inc.
  More Information

No publications provided

Responsible Party: Hospira, Inc.
ClinicalTrials.gov Identifier: NCT00652028     History of Changes
Other Study ID Numbers: DEX-08-01
Study First Received: April 1, 2008
Last Updated: September 6, 2011
Health Authority: United States: Food and Drug Administration
Guatemala: Ministry of Public Health and Social Assistance

Keywords provided by Hospira, Inc.:
Pharmacokinetics
Pharmacodynamics
Escalating dose
Dexmedotimidine
Intubated
Mechanically ventilated
Pediatrics

Additional relevant MeSH terms:
Dexmedetomidine
Midazolam
Adjuvants, Anesthesia
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014