- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00652028
Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects
March 16, 2017 updated by: Hospira, now a wholly owned subsidiary of Pfizer
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
The objective of this study is to characterize the pharmacokinetic and pharmacodynamic profile of dexmedetomidine administered as an intravenous loading dose followed by a continuous intravenous infusion in pediatric subjects ages ≥2 through <17 years old.
Study Overview
Status
Completed
Intervention / Treatment
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 ≥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 ≥2 through <6 years old and Group II subjects age ≥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.
Study Type
Interventional
Enrollment (Actual)
69
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Guatemala City, Guatemala
- Unidad Cirugia Cardiovascular de Guatemala
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Florida
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Miami, Florida, United States, 33155
- Miami Children's Hospital
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Kentucky
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Louisville, Kentucky, United States, 40202
- University of Louisville/Kosair Children's Hospital
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New York
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Buffalo, New York, United States, 14222
- Women and Children's Hospital of Buffalo
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, United States, 15213
- Children's Hospital of Pittsburgh
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Virginia
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Richmond, Virginia, United States, 23219
- Virginia Commonwealth University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 16 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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:
- ≥2 years old through <6 years old
- ≥6 years old through <17 years old
If female, subject is non-lactating and is either:
- Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.
- 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
- Diminished consciousness from increased intracranial pressure.
- Extensive brain surgery (surgery requiring intracranial pressure monitor).
- Diminished cognitive function per PI's discretion.
- Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
- Weight <10 kg.
- Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
- Hepatic impairment Serum glutamic pyruvic transaminase/Alanine aminotransferase (SGPT/ALT) >100 U/L
Hypotension based on repeat assessments prior to starting study drug:
- Age ≥2 years old through ≤12 years old: systolic blood pressure (SBP) <80 mmHg
- Age >12 years old through <17 years old: SBP <90 mmHg
Pre-existing bradycardia prior to starting study drug defined as:
- Age ≥2 years old through ≤6 years old: ≤70 beats per minute (bpm)
- Age >6 years old through ≤12 years old: ≤60 bpm
- Age >12 years old through ≤16 years old: ≤50 bpm
- Acute thermal burns involving more than 15 percent total body surface area.
- Subjects who have a known allergy to dexmedetomidine, midazolam (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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Group 1
Dose level 1
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Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
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Other: Group 2
Dose level 2
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Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
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Other: Group 3
Dose level 3
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Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
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Other: Group 4
Dose level 4
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Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t)
Time Frame: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Area under the concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) for Dexmedetomidine
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≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Area Under the Concentration-time Curve From Time Zero to the Time Infinity (AUC0-∞)
Time Frame: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
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Area under the concentration-time curve from time zero to the time infinity (AUC0-∞) for Dexmedetomidine
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≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
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Observed Peak Plasma Concentration
Time Frame: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
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Observed peak plasma concentration (Cmax) for Dexmedetomidine
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≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
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Terminal Elimination Half-life (t1/2)
Time Frame: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Terminal elimination half-life (t1/2) for Dexmedetomidine
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≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Plasma Concentration at Steady State (Css)
Time Frame: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Plasma concentration at steady state (Css) for Dexmedetomidine
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≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Volume of Steady State Distribution (Vss)
Time Frame: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Volume of steady state distribution (Vss) for Dexmedetomidine
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≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Clearance (CL)
Time Frame: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Clearance (CL) for Dexmedetomidine
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≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
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Level of Sedation Based on Average Ramsay Sedation Scale (RSS) Score
Time Frame: Prior to loading (Baseline), 5 and 10 min during the load, at start of maintenance infusion and every 15 min for 1 hour, hourly during the maintenance period, before and within 5 min after midazolam or fentanyl dose during the dexmedetomidine infusion.
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RSS Score range from 1 to 6:
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Prior to loading (Baseline), 5 and 10 min during the load, at start of maintenance infusion and every 15 min for 1 hour, hourly during the maintenance period, before and within 5 min after midazolam or fentanyl dose during the dexmedetomidine infusion.
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Number of Subjects Who Received Rescue Medication for Sedation (Midazolam) and Analgesics (Fentanyl)
Time Frame: During the treatment period (Approximately 24 hours)
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Number of subjects who received rescue medication for Sedation (Midazolam) and analgesics (Fentanyl) while intubated during Treatment Period
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During the treatment period (Approximately 24 hours)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2008
Primary Completion (Actual)
April 1, 2010
Study Completion (Actual)
April 1, 2010
Study Registration Dates
First Submitted
April 1, 2008
First Submitted That Met QC Criteria
April 2, 2008
First Posted (Estimate)
April 3, 2008
Study Record Updates
Last Update Posted (Actual)
April 13, 2017
Last Update Submitted That Met QC Criteria
March 16, 2017
Last Verified
August 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Analgesics, Non-Narcotic
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Analgesics, Opioid
- Narcotics
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Fentanyl
- Midazolam
- Dexmedetomidine
Other Study ID Numbers
- DEX-08-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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