Conditions: Intubated and Mechanically Ventilated Pediatric Subjects
Keywords: Pharmacokinetics Pharmacodynamics Escalating dose Dexmedotimidine Intubated Mechanically ventilated Pediatrics
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 69
Healthy volunteers: no

Brief summary:
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.

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.

Arms:
arm 1: Dose level 1 arm 2: Dose level 2 arm 3: Dose level 3 arm 4: Dose level 4

Interventions: intervention 1: Dexmedetomidine, midazolam; fentanyl
Intervention descriptions: intervention 1: Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label

Protocol document: