Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal

NCT01945736 | Completed DMC

• 2 other identifiers: Pro00044082HHSN27500021
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 5

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.

Conditions

Opiate Withdrawal Syndrome

Keywords

Opiate withdrawal in children

Outcome Measures

Primary Outcomes (1)

• PK Parameters after multiple doses of enteral methadone

  * Apparent oral clearance * Apparent oral volume of distribution * Area under the curve * Absorption rate constant

  Maximum of 7 PK samples based on dosing schedule collected over a 5 day period

Secondary Outcomes (7)

• PK of methadone's primary metabolite EDDP

  Maximum of 7 PK samples based on dosing schedule collected over a 5 day period

• PK of R- and S-enantiomers of methadone

  Maximum of 7 PK samples based on dosing schedule collectes over a 5 day period

• Correlation between plasma and DBS samples

  Maximum of 7 PK samples based on dosing schedule collected over a 5 day period

• Correlation between plasma and scavenge samples

  Maximum of 7 PK samples based on dosing schedule collected over a 5 day period

• Influence of CYP3A4 and CYP3B6 genetic polymorphisms on methadone PK

  Maximum of 7 PK samples based on dosing schedule collected over a 5 day period

Study Arms (3)

Cohort 1

\> or = 90 days to \< 2 years on enteral methadone. Dose schedule is per routine medical care.

Drug: Methadone

Cohort 2

2 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.

Drug: Methadone

Cohort 3

6 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.

Drug: Methadone

Interventions

Methadone DRUG

To determine the PK of enteral methadone in children \> or = 90 days and \<18 years treated for opiate withdrawal per routine medical care.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 91 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• \>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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kevin Watt: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (5)

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Mercy Hospital

Kansas City, Kansas, 64108, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27701, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

The Study team is interested in learning more about how genetic differences in proteins known as cytochrome P450 enzymes effect the breakdown of methadone. The study team will gather leftover blood collected from the infant or child while the infant/child was in this study and send it to a laboratory to test for genetics. There will be no extra blood draws for this part of the study. The samples for genetic testing will be given a code number and will not be labeled with the infant or child's name or initials, or any other information that could identify the infant or child. Any remaining blood will be destroyed after the genetic laboratory testing is complete.

MeSH Terms

Interventions

Methadone

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• Kevin watt, MD

  Duke Medical Center/Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 19, 2013
• Study Start: January 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: December 24, 2018

Record last verified: 2018-12

Locations

US (5)