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Effect on Acetaminophen Metabolism by Liquid Formulations

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01246713
First Posted: November 23, 2010
Last Update Posted: May 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Harvard University
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Michael Ganetsky, Beth Israel Deaconess Medical Center
  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
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
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 Michael Ganetsky, Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Acetaminophen Metabolites [ Time Frame: 8 hours ]
    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

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Michael Ganetsky, MD Beth Israel Deaconess Medical Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Ganetsky, Assistant Professor of Emergency Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01246713     History of Changes
Other Study ID Numbers: 2010P000135
UL1RR025758 ( U.S. NIH Grant/Contract )
First Submitted: November 22, 2010
First Posted: November 23, 2010
Results First Submitted: February 18, 2013
Results First Posted: May 8, 2013
Last Update Posted: May 8, 2017
Last Verified: March 2017

Keywords provided by Michael Ganetsky, Beth Israel Deaconess Medical Center:
acetaminophen
excipients

Additional relevant MeSH terms:
Poisoning
Chemically-Induced Disorders
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics