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Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months

29 de junio de 2015 actualizado por: Hospira, now a wholly owned subsidiary of Pfizer

A Phase II, Randomized, Open-Label, Single Center, Pharmacokinetic and Pharmacodynamic Study of Dexmedetomidine in Pediatric Subjects Aged 12 Months Through <24 Months

The purpose of this study is to investigate the pharmacokinetic, pharmacodynamic, and safety of dexmedetomidine at 2 different dose levels in pediatric subjects, aged 12 months through <24 months, administered as an intravenous loading dose followed by continuous infusion for a minimum of 6 hours and up to 24 hours in an intensive care setting.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

Phase II, randomized, open-label, single-center, study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects across two dose levels (Dose Level 1 consists of a 0.7 mcg/kg loading dose immediately followed by a 0.5 mcg/kg/hr maintenance infusion; Dose Level 2 consists of a 1.0 mcg/kg loading dose immediately followed by a 0.75 mcg/kg/hr maintenance infusion). The study population will consist of intubated and mechanically ventilated pediatric subjects who require sedation in an intensive care setting for a minimum of 6 hours but not to exceed 24 hours. Subjects eligible for enrollment are 12 months to <24 months of age.

Tipo de estudio

Intervencionista

Inscripción (Actual)

5

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Estados Unidos, 15224
        • Children's Hospital of Pittusburgh of UPMC

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

1 año a 1 año (Niño)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Subject is 12 months to <24 months of age at screening.
  2. Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
  3. Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
  4. The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.

Exclusion Criteria:

  1. Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:

    • Diminished consciousness from increased intracranial pressure
    • Extensive brain surgery (surgery requiring intracranial pressure monitor)
    • Diminished cognitive function per Principal Investigator (PI) discretion
    • Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
  2. Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.
  3. Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.
  4. Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.
  5. Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.
  6. Subject who have acute thermal burns involving more than 15 percent total body surface area.
  7. Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.
  8. Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.
  9. Subjects with a life expectancy that is <72 hours.
  10. Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.
  11. Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.
  12. Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).
  13. Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.
  14. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Dose level 1
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
Droga: Dexmedetomidine
For sedation according to protocol
Experimental: Dose level 2
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
Droga: Dexmedetomidine
For sedation according to protocol

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration-time Curve (AUC0-∞)
Periodo de tiempo: 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
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
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
Observed Peak Plasma Concentration (Cmax)
Periodo de tiempo: 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
Maximum observed concentration of dexmedetomidine in plasma
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
Steady State Concentration (Css)
Periodo de tiempo: 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
Concentration of dexmedetomidine at steady state in plasma
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
Terminal Elimination Half-life (t1/2)
Periodo de tiempo: 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
Terminal elimination half-life of dexmedetomidine. Half-life is the time required for plasma concentration of the drug to decrease by 50%.
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
Time to Reach Maximum Plasma Concentration (Tmax)
Periodo de tiempo: 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
Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours
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
Weight-Adjusted Plasma Clearance (CLw)
Periodo de tiempo: 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
Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.
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
Plasma Clearance (CL)
Periodo de tiempo: 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
Clearance of dexmedetomidine after intravenous administration. Clearance is the rate at which the drug is removed from the plasma after the dose.
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
Volume of Distribution (Vd)
Periodo de tiempo: 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
Volume of distribution of dexmedetomidine after intravenous administration. Volume of distribution measures how much the drug spreads through the body after the dose.
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
Weight-Adjusted Volume of Distribution (Vdw)
Periodo de tiempo: 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
Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.
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
Average Total Faces, Legs, Activity, Cry, and Consolability (FLACC) Score
Periodo de tiempo: 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 fentanyl
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.
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 fentanyl
Absolute Time That Subject is in UMSS Range 2-4 During Treatment Period
Periodo de tiempo: During the treatment (6 to 24 hours)

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.
During the treatment (6 to 24 hours)
Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
Periodo de tiempo: During the treatment (6 to 24 hours)
Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion
During the treatment (6 to 24 hours)

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Hospira, now a wholly owned subsidiary of Pfizer

Investigadores

  • Investigador principal: Constantinos Chrysostomou, MD, Children's Hospital of Pittusburgh of UPMC

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de junio de 2011

Finalización primaria (Actual)

1 de agosto de 2011

Finalización del estudio (Actual)

1 de agosto de 2011

Fechas de registro del estudio

Enviado por primera vez

20 de junio de 2011

Primero enviado que cumplió con los criterios de control de calidad

22 de junio de 2011

Publicado por primera vez (Estimar)

23 de junio de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

24 de julio de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

29 de junio de 2015

Última verificación

1 de junio de 2015

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • DEX-11-01

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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