Metabolism and Toxicity of Acetaminophen

NCT01328808 | Unknown Phase 2 FDA Drug

• 1 other identifier: 4839 - APAP
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate how acetaminophen (APAP) is released into the urine and blood; to determine how the blood levels of acetaminophen and its breakdown products affect the preterm infant's health; to decrease adverse drug reactions; and to collect data on how the genetic make-up or characteristics affect how APAP is handled within the preterm infant. By taking several blood and urine samples during the study, we will be able to check the blood levels (called pharmacokinetics) of APAP in preterm babies.

Conditions

Pain

Keywords

Acetaminophen; Preterm Infants

Outcome Measures

Primary Outcomes (1)

• primary endpoint PK analysis

  Blood and urine levels of APAP and metabolites

  48 hours

Secondary Outcomes (1)

• Developmental stage

  48 hours

Study Arms (1)

group 2 Pain management

EXPERIMENTAL

In preterm and term neonates with a GA of 28 weeks or more a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute. In preterm and term neonates with a GA of less than 28 weeks 15 mg/kg dose of APAP will be given every 12 hrs by an intravenous infusion over 30-minute

Drug: Acetaminophen/APAP

Interventions

Acetaminophen/APAP DRUG

In preterm and term neonates with a GA of 28 weeks or more a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute. In preterm and term neonates with a GA of less than 28 weeks a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute

Also known as: Tylenol

group 2 Pain management

Eligibility Criteria

• Age: 22 Weeks - 37 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm and term neonates of both genders and all races
• a postnatal age of less than 28 days
• GA's of from 22 to less than 37 weeks
• an indwelling (peripheral or umbilical) arterial line
• a clinical indication for intravenous administration of pain relief medication

You may not qualify if:

• Neonates with severe asphyxia
• grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations (e.g., cleft lip and palate),
• neurological disorders
• those receiving continuous or intermittent neuromuscular blockers
• clinical or biochemical evidence of hepatic renal failure (including systemic hypoperfusion)

Sponsors & Collaborators

• John van den Anker: lead

Study Sites (2)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Childrens Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (3)

• Cook SF, Stockmann C, Samiee-Zafarghandy S, King AD, Deutsch N, Williams EF, Wilkins DG, Sherwin CM, van den Anker JN. Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model. Clin Pharmacokinet. 2016 Nov;55(11):1395-1411. doi: 10.1007/s40262-016-0408-1.

  PMID: 27209292 RESULT

• Cook SF, King AD, van den Anker JN, Wilkins DG. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 15;1007:30-42. doi: 10.1016/j.jchromb.2015.10.013. Epub 2015 Oct 31.

  PMID: 26571452 RESULT

• Cook SF, Roberts JK, Samiee-Zafarghandy S, Stockmann C, King AD, Deutsch N, Williams EF, Allegaert K, Wilkins DG, Sherwin CM, van den Anker JN. Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation. Clin Pharmacokinet. 2016 Jan;55(1):107-19. doi: 10.1007/s40262-015-0301-3.

  PMID: 26201306 RESULT

MeSH Terms

Conditions

Pain

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• John N van den Anker, MD, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 5, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 2, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

US (2)