Codeine in Mechanically Ventilated Neonates

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Overall Status

Completed

CT.gov ID

NCT01322204

Collaborator

(none)

Enrollment

Location

Arm

55.1

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Mechanically Ventilated Neonates Painful Procedures in Newborns	Drug: Codeine	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Absorption and Metabolism of Oral Codeine in Mechanically Ventilated Neonates

Study Start Date :

Aug 1, 2008

Actual Primary Completion Date :

Mar 6, 2013

Actual Study Completion Date :

Mar 6, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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. [2 hours]

Secondary Outcome Measures

Secondary outcomes include the additional PK parameters elimination half life, area under the curve and mean residence time. [2 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 30 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	State University of New York Downstate	Brooklyn	New York	United States	11203

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator: Jacob V Aranda, MD, PhD, State University of New York Downstate

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jacob Aranda, Principal Investigator, State University of New York - Downstate Medical Center

ClinicalTrials.gov Identifier:

NCT01322204

Other Study ID Numbers:

10922

First Posted:

Mar 24, 2011

Last Update Posted:

Aug 27, 2018

Last Verified:

Aug 1, 2018

Keywords provided by Jacob Aranda, Principal Investigator, State University of New York - Downstate Medical Center

codeine, neonates, pediatric pharmacology

Additional relevant MeSH terms:

Codeine

Study Results

No Results Posted as of Aug 27, 2018