Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal

Condition(s) targeted: Opiate Withdrawal Syndrome

Intervention: Methadone (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Phillip Brian Smith

Official(s) and/or principal investigator(s):
P. Brian Smith, MD, MHS, MPH, Principal Investigator, Affiliation: Duke Medical Center/Duke Clinical Research Institute

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.

Official title: Pharmacokinetics of Multiple Dose Methadone in Children

Study design: Observational Model: Cohort, Time Perspective: Prospective

Primary outcome: PK Parameters after multiple doses of enteral methadone

Secondary outcome:

PK of methadone's primary metabolite EDDP

PK of R- and S-enantiomers of methadone

Correlation between plasma and DBS samples

Correlation between plasma and scavenge samples

Influence of CYP3A4 and CYP3B6 genetic polymorphisms on methadone PK

Methadone pharmacodynamics using the WAT-1

Adverse events

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.

Minimum age: 91 Days. Maximum age: 18 Years. Gender(s): Both.

Criteria:

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

All Children's Hospital, St. Petersburg, Florida 33701, United States

Children's Mercy Hospital, Kansas City, Kansas 64108, United States

C.S. Mott Children's Hospital, Ann Arbor, Michigan 48109, United States

Duke University Medical Center, Durham, North Carolina 27701, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

Starting date: January 2014
Last updated: March 4, 2015