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Effect on Acetaminophen Metabolism by Liquid Formulations

This study has been completed.
Sponsor:
Collaborators:
Harvard University
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01246713
First received: November 22, 2010
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to determine whether excipients in the liquid formulation of acetaminophen prevent the formation of the toxic metabolites of acetaminophen.


Condition Intervention
Acetaminophen Metabolism
Acetaminophen Poisoning
Drug Metabolism by Excipients
Drug: Acetaminophen liquid formulation
Drug: Acetaminophen solid formulation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Effect on Acetaminophen Metabolism by Liquid Formulations: Do Excipients in Liquid Formulation Prevent Production of Toxic Metabolites?

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Acetaminophen Metabolites [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Area-under-curve from time zero to 8 hours for APAP-cysteinate metabolite. Serum was collected just prior to and at hours 1, 2, 4, 6, and 8 after administration of the APAP dose.


Enrollment: 15
Study Start Date: December 2010
Study Completion Date: July 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Acetaminophen solid formulation
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
Drug: Acetaminophen solid formulation
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
Active Comparator: Acetaminophen liquid formulation
Subjects in this arm will receive a 15mg/kg dose of a liquid acetaminophen formulation.
Drug: Acetaminophen liquid formulation
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.

Detailed Description:

Acetaminophen (APAP) poisoning is the most frequent cause of acute hepatic failure in the United States. Toxicity requires cytochrome P-450 bioactivation of APAP. Children are less susceptible to APAP toxicity; the current theory is that they have different metabolism than adults. However, children's liquid preparations of APAP contain excipients which have been shown to inhibit APAP bioactivation in vitro and in rodents. Children tend to ingest liquid preparations, which could potentially explain their decreased susceptibility instead of an intrinsically different metabolism. Further, our review of Poison Center epidemiologic data shows that liquid preparations are less toxic in adults. Our hypothesis is that excipients in liquid preparations inhibit the bioactivation of APAP. The design is a pharmacokinetic cross-over study in humans. Healthy adult subjects will be recruited for administration of therapeutic doses of APAP in capsule and liquid formulations. Plasma via a heplock will be collected at serial time points up to 8 hours and assayed for APAP and its metabolites. After a washout period, subjects will receive the same dose of APAP in the alternate preparation. The pattern of metabolites, indicating the activity of the bioactivating enzymes, will be compared. A significant difference in P-450 metabolites will support the hypothesis and provide preliminary data for studies in patients who have ingested potentially toxic doses of APAP. Ultimately, this work could support development of novel antidotal therapy for APAP overdose.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteer ages 18-40
  • Not taking any chronic medications

Exclusion Criteria:

  • Pregnancy
  • Any history of liver disease
  • Frequent alcohol use (2 or more drinks more than 4 times per week)
  • Unable to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246713

Locations
United States, Massachusetts
Harvard - Thorndike Clinical Research Center at Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Harvard University
Investigators
Principal Investigator: Michael Ganetsky, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided by Beth Israel Deaconess Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01246713     History of Changes
Other Study ID Numbers: 2010P-000135, UL1RR025758
Study First Received: November 22, 2010
Results First Received: February 18, 2013
Last Updated: March 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
acetaminophen
excipients

Additional relevant MeSH terms:
Acetaminophen
Analgesics
Analgesics, Non-Narcotic
Antipyretics
Central Nervous System Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014