Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal

Opiate Withdrawal Syndrome Clinical Trial

— MTH01  

Official title:

Pharmacokinetics of Multiple Dose Methadone in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01945736
• Other study ID #: Pro00044082
• Secondary ID: HHSN27500021
• Status: Completed
• Start date: January 2014
• Est. completion date: February 2015

Study information

• Verified date: December 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 91 Days to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Opiate Withdrawal Syndrome
• Substance Withdrawal Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Children's Mercy Hospital	Kansas City	Kansas
United States	All Children's Hospital	Saint Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Kevin Watt	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	PK of methadone's primary metabolite EDDP		Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Secondary	PK of R- and S-enantiomers of methadone		Maximum of 7 PK samples based on dosing schedule collectes over a 5 day period
Secondary	Correlation between plasma and DBS samples		Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Secondary	Correlation between plasma and scavenge samples		Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Secondary	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
Secondary	Methadone pharmacodynamics using the WAT-1		Maximum of 7 PK samples based on dosing schedule collected over a 5 day period
Secondary	Adverse events		Study days 1-5 and observational days 6-10