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Codeine in Mechanically Ventilated Neonates

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Jacob Aranda, State University of New York - Downstate Medical Center
ClinicalTrials.gov Identifier:
NCT01322204
First received: March 22, 2011
Last updated: February 7, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to determine the absorption and bioavailability of codeine in relation to postnatal (PNA) and postconceptional (PCA) age; determine the parent drug (codeine), its active metabolites, their formation rates and their ratios in relation with PCA and PNA; and identify relevant genetic polymorphisms of opioid metabolism in the study population and their potential relationship to the biodisposition and pharmacodynamic effects of codeine. The study population is intubated and mechanically ventilated infants equal to or greater than 26 weeks gestational age at birth and less than 4 weeks postnatal age.


Condition Intervention Phase
Mechanically Ventilated Neonates,
Painful Procedures in Newborns
Drug: Codeine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Absorption and Metabolism of Oral Codeine in Mechanically Ventilated Neonates

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • The rate and extent of absorption of oral codeine, the ratios of the observed concentration of each metabolite to the observed concentration of parent drug and the formation and clearances of the metabolites. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary outcomes include the additional PK parameters elimination half life, area under the curve and mean residence time. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: August 2008
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Neonates 0-30 days, no more than 2,000 grams, receiving mechanical ventilation.
Drug: Codeine
One single oral dose of 1 mg/kg of codeine

Detailed Description:

This proposal has its origins in a larger initiative to elucidate the pharmacological basis for the interindividual differences observed in opioid responsiveness. Gaps in our knowledge related to opioid disposition in newborns need to be addressed to complete the design of the required overarching initiative in which age could be treated as a continuous variable within a context of PK, PD and PG determinants.This proposal is designed to generate preliminary data that addresses two issues. First, can newborns absorb enterally administered codeine and is this ability determined by PCA or PNA age? The second relates to the ability of newborn infants to catalyze those reactions required to metabolically activate both codeine and morphine. The latter will also be evaluated within the context of PCA versus PNA age.

These data will not only fill an information gap that must be addressed before the larger initiative moves forward, but they also provide a platform for serious study of the ontogeny of certain pharmacokinetic processes that may prove critical to our understanding of newborn drug disposition. In this way, codeine can provide important insights concerning the ontogeny of drug disposition and permit the determination of the relative importance of PCA versus PNA ages to the functional expression of these processes.

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates ≥ 26 weeks PCA receiving mechanical ventilation and painful procedure will be eligible for participation in the study
  • Subject's parent/legal guardian must give written informed consent prior to study participation
  • Subject is receiving opioid analgesia therapy based on caregiver determination. The ideal patient will not be receiving morphine.
  • Must be able to receive an enteral dose of codeine.

Exclusion Criteria:

  • Known hypersensitivity to morphine, fentanyl, or codeine
  • Patients with ALT concentrations >2x upper limit of normal for age or clinical evidence of hepatic failure
  • Patients with serum creatinine concentrations >2x upper limit of normal for age or clinical evidence of renal failure
  • Patients who are NPO
  • Babies born to maternal drug abuse.
  • Total serum bilirubin level of > 10 mg/dl or 170 umol/L.
  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: NCT01322204

Contacts
Contact: Jacob V Aranda, MD, PhD 718-270-3092 jaranda@downstate.edu
Contact: Jeffrey L Blumer, MD, PhD 216-844-3310 jeffrey.blumer@uhhospitals.org

Locations
United States, New York
State University of New York Downstate Recruiting
Brookyln, New York, United States, 11203
Sponsors and Collaborators
Investigators
Principal Investigator: Jacob V Aranda, MD, PhD State University of New York Downstate
  More Information

No publications provided

Responsible Party: Jacob Aranda, Principal Investigator, State University of New York - Downstate Medical Center
ClinicalTrials.gov Identifier: NCT01322204     History of Changes
Other Study ID Numbers: 10922
Study First Received: March 22, 2011
Last Updated: February 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
codeine, neonates, pediatric pharmacology

Additional relevant MeSH terms:
Pharmacologic Actions
Codeine
Analgesics
Analgesics, Opioid
Antitussive Agents
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014