Clinical trial NCT01945736: Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal
Official title: Pharmacokinetics of Multiple Dose Methadone in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Opiate Withdrawal Syndrome
Keywords: Opiate withdrawal in children
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-09-19
Enrollment: 26
Sex: ALL
Minimum age (years): 91
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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

Primary outcomes:
measure: PK Parameters after multiple doses of enteral methadone
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Secondary outcomes:
measure: PK of methadone's primary metabolite EDDP
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
measure: PK of R- and S-enantiomers of methadone
timeFrame: Maximum of 7 PK samples based on dosing schedule collectes over a 5 day period
measure: Correlation between plasma and DBS samples
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
measure: Correlation between plasma and scavenge samples
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
measure: Influence of CYP3A4 and CYP3B6 genetic polymorphisms on methadone PK
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
measure: Methadone pharmacodynamics using the WAT-1
timeFrame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
measure: Adverse events
timeFrame: Study days 1-5 and observational days 6-10
Other outcomes:
Locations:
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Kansas
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Duke Medical Center/Duke Clinical Research Institute
name: Kevin watt, MD
role: PRINCIPAL_INVESTIGATOR
References: