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Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal

Completed
Conditions
Opiate Withdrawal Syndrome
Interventions
Registration Number
NCT01945736
Lead Sponsor
Kevin Watt
Brief Summary

The purpose of this study is to learn more about how the study drug, methadone, prescribed by an infant's or child's physician as part of standard medical care, is processed in children and young adults. While this drug is used extensively in infants and children, it has not been extensively studied in this population.

Physicians do not have very much information on how long it takes for methadone to be removed from the blood circulation and passed out of the body. Physicians need more information to guide how much and how often we should give methadone to children/young adults to ensure they get the maximum effect with the minimum amount of drug. During this research study, the study team will collect information about how this drug is processed in infants and children.

Detailed Description

A total of approximately 24 to 36 infants and children will participate in this study. This study will be done at five medical centers in the United States.

Treatment will be prescribed by the infant or child's doctor and not by the study team.

Participants will be divided into 3 groups based on age, ages 3 months to 2 years, ages 2 to 6 years, and ages 6 to 18 years. There will be approximately 8 to 12 participants enrolled in each group. Additionally, at least 6 overweight or obese participants between ages 2-18 years will be included in this study.

Information collected from each subject's routine medical care will include:

* Participant gender, date of birth, race and ethnicity

* Pertinent medical history

* Laboratory results (blood count and chemistries) from routine testing ordered by the infant or child's regular doctor

* Medications of interest the child was given within the 72 hours prior to first dose of methadone administered after consent

* Time and dose of methadone administered to the child up to 14 days prior to enrollment

Study specific information collected will include:

* Blood sample collection to measure level of methadone

* Baseline WAT-1 score (sedation withdrawal assessment of the infant or child used to assess symptoms the child/infant may experience when opioid drugs are discontinued).

The duration of the study will be up to 10 days, comprised of a maximum 5 day treatment period a 5 day observation period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
Inclusion Criteria
  • >90 days - < 18 years of age at the time of first dose of study drug
  • Receiving enteral methadone as standard of care
  • Signed informed consent/HIPAA documents by the parent/legal guardian and assent (if applicable)
Exclusion Criteria
  • Previous participation in the study
  • Subject is receiving ECLS (Extracorporeal Life Support)
  • < 36 weeks gestational age at birth for children <1 year of age at time of enrollment
  • Any other condition or chronic illness that in the opinion of the Principal
  • Investigator makes participation unadvised or unsafe

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Cohort 1Methadone\> or = 90 days to \< 2 years on enteral methadone. Dose schedule is per routine medical care.
Cohort 2Methadone2 years to \< 6 years on enteral methadone. Dose schedule is per routine medical care. Will include overweight children with BMI for age of 85 - 95 percentile, or obese children BMI for age \> or = to 95 percentile.
Cohort 3Methadone6 years to \< 18 years on enteral methadone. Dose schedule is per routine medical care. Will include overweight children with BMI for age of 85 - 95 percentile, or obese children BMI for age \> or = to 95 percentile.
Primary Outcome Measures
NameTimeMethod
PK Parameters after multiple doses of enteral methadoneMaximum of 7 PK samples based on dosing schedule collected over a 5 day period

* Apparent oral clearance

* Apparent oral volume of distribution

* Area under the curve

* Absorption rate constant

Secondary Outcome Measures
NameTimeMethod
Correlation between plasma and scavenge samplesMaximum of 7 PK samples based on dosing schedule collected over a 5 day period
PK of methadone's primary metabolite EDDPMaximum of 7 PK samples based on dosing schedule collected over a 5 day period
PK of R- and S-enantiomers of methadoneMaximum of 7 PK samples based on dosing schedule collectes over a 5 day period
Correlation between plasma and DBS samplesMaximum of 7 PK samples based on dosing schedule collected over a 5 day period
Influence of CYP3A4 and CYP3B6 genetic polymorphisms on methadone PKMaximum of 7 PK samples based on dosing schedule collected over a 5 day period
Methadone pharmacodynamics using the WAT-1Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Adverse eventsStudy days 1-5 and observational days 6-10

Trial Locations

Locations (5)

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

C.S. Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

All Children's Hospital

🇺🇸

Saint Petersburg, Florida, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Kansas, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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