Trial Outcomes & Findings for Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months (NCT NCT01378988)
NCT ID: NCT01378988
Last Updated: 2015-07-24
Results Overview
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
COMPLETED
PHASE2
5 participants
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
2015-07-24
Participant Flow
Participant milestones
| Measure |
Dose Level 1
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
3
|
|
Overall Study
COMPLETED
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
1.43 years
STANDARD_DEVIATION 0.312 • n=5 Participants
|
1.45 years
STANDARD_DEVIATION 0.274 • n=7 Participants
|
1.44 years
STANDARD_DEVIATION 0.249 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC0-∞)
|
4639.17 picogram*hour per millilitre
Standard Deviation 4058.1893
|
14203.544 picogram*hour per millilitre
Standard Deviation 13051.6850
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Maximum observed concentration of dexmedetomidine in plasma
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Observed Peak Plasma Concentration (Cmax)
|
4499.925 picogram per millilitre
Standard Deviation 5826.7367
|
11737.387 picogram per millilitre
Standard Deviation 3549.7923
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Concentration of dexmedetomidine at steady state in plasma
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Steady State Concentration (Css)
|
752.298 picogram per millilitre
Standard Deviation 658.0848
|
2303.277 picogram per millilitre
Standard Deviation 2116.4895
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Terminal elimination half-life of dexmedetomidine. Half-life is the time required for plasma concentration of the drug to decrease by 50%.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Terminal Elimination Half-life (t1/2)
|
1.958 Hours
Standard Deviation 0.3765
|
2.260 Hours
Standard Deviation 1.2205
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax)
|
0.083 Hours
Standard Deviation 0.0
|
0.283 Hours
Standard Deviation 0.3464
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Weight-Adjusted Plasma Clearance (CLw)
|
1.292 Litre per Hours per Kilogram
Standard Deviation 1.1300
|
0.617 Litre per Hours per Kilogram
Standard Deviation 0.3815
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Clearance of dexmedetomidine after intravenous administration. Clearance is the rate at which the drug is removed from the plasma after the dose.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Plasma Clearance (CL)
|
12.192 Litre per Hour
Standard Deviation 9.5770
|
5.836 Litre per Hour
Standard Deviation 2.9357
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Volume of distribution of dexmedetomidine after intravenous administration. Volume of distribution measures how much the drug spreads through the body after the dose.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Volume of Distribution (Vd)
|
31.845 Litre
Standard Deviation 20.4351
|
15.780 Litre
Standard Deviation 3.5461
|
PRIMARY outcome
Timeframe: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MIPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Weight-Adjusted Volume of Distribution (Vdw)
|
3.343 Litre per Kilogram
Standard Deviation 2.4910
|
1.590 Litre per Kilogram
Standard Deviation 0.6201
|
PRIMARY outcome
Timeframe: Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanylPopulation: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
FLACC scale is a 5 category observational measure to assess pediatric pain on face, legs, activity, cry and consolability. Responses in each category are scored between 0 to 2 (0 = normal, relaxed to 2 = upset, rigid), for a maximum total score of 10.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Average Total Faces, Legs, Activity, Cry, and Consolability (FLACC) Score
|
1.575 units on a scale
Standard Deviation 2.2274
|
3.220 units on a scale
Standard Deviation 2.1707
|
PRIMARY outcome
Timeframe: During the treatment (6 to 24 hours)Population: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate PK samples to estimate primary parameters.
The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper physical stimuli); Score 4 (unarousable). The UMSS scores obtained just prior the loading dose (LD) and 5 and 10 minutes during LD; 0, 5, 10, 15, 30, and 60 minutes and thereafter every 4 hours of the maintenance infusion; within 5 minutes of obtaining each pharmacokinetic sample; within 5 minutes prior and after any midazolam rescue during dexmedetomidine infusion period.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Absolute Time That Subject is in UMSS Range 2-4 During Treatment Period
|
3.6 Hours
Standard Deviation 3.48
|
5.8 Hours
Standard Deviation 0.38
|
PRIMARY outcome
Timeframe: During the treatment (6 to 24 hours)Population: Full Evaluable Population consisted of all subjects who received study drug for at least 5 hours with adequate pharmacokinetic samples to estimate primary parameters.
Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
Dose Level 2
n=3 Participants
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
|---|---|---|
|
Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
Midazolam for sedation
|
1 participants
|
1 participants
|
|
Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
Fentanyl for Analgesic
|
1 participants
|
2 participants
|
Adverse Events
Dose Level 1
Dose Level 2
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dose Level 1
n=2 participants at risk
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance dose
|
Dose Level 2
n=3 participants at risk
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance dose
|
|---|---|---|
|
General disorders
Pyrexia
|
0.00%
0/2
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/2
|
33.3%
1/3
|
Additional Information
Marcelo Garcia de Rocha MD, Global Medical Director
Hospira
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place