Acetaminophen Adduct Formation in Non-Drinkers Taking Therapeutic Doses of Acetaminophen for Ten Consecutive Days

This study has been completed.
Sponsor:
Collaborator:
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by (Responsible Party):
Kennon Heard, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier:
NCT00616018
First received: February 4, 2008
Last updated: July 10, 2012
Last verified: July 2012
  Purpose

Acetaminophen is commonly used to treat fever or pain. Your body clears acetaminophen by processing it in the liver. During the processing, some of the acetaminophen may bind to proteins in the liver. The protein-acetaminophen product is called an "adduct." After a large acetaminophen overdose, the liver has to process a lot of acetaminophen, so large amounts of adducts are formed. However, we have found that lower levels may be formed even when people take recommended doses. The purpose of this study is to measure the amount of adducts formed when healthy people who do not drink alcohol take normal doses of acetaminophen for 10 days.


Condition Intervention Phase
Drug Induced Liver Injury
Drug: acetaminophen
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Acetaminophen Adduct Formation in Alcohol Abstaining Subjects Administered Therapeutic Doses of Acetaminophen for Ten Consecutive Days

Resource links provided by NLM:


Further study details as provided by Denver Health and Hospital Authority:

Primary Outcome Measures:
  • Serum Level of Acetaminophen-cysteine (APAP-Cys) Protein Adducts [ Time Frame: Day 0, 4, 7, 9, 11, and 14. ] [ Designated as safety issue: Yes ]
    Acetaminophen-cysteine (APAP-Cys) protein adduct concentrations were measured at Day 0, 4, 7, 9, 11 and 14. All units are in nmol/mL serum.


Secondary Outcome Measures:
  • Alanine Aminotransferase (ALT) [ Time Frame: Day 0, 4, 7, 9, 11, and 14. ] [ Designated as safety issue: Yes ]
    ALT was measured at Day 0, 4, 7, 9, 11, and 14.


Enrollment: 35
Study Start Date: August 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
all subjects receive 4 g/day of acetaminophen for 10 consecutive days in this open-label study
Drug: acetaminophen
4 g/day for 10 consecutive days
Other Name: Tylenol Extra Strength

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. age 21 years or older
  2. provide written informed consent
  3. consume, on average, less than 1 alcoholic beverage daily for the previous 3 months and would be considered non-drinkers

Exclusion Criteria:

  1. History of ingesting more than 4 grams of acetaminophen per day for any of the 4 days preceding study enrollment
  2. Currently taking isoniazid
  3. Consumption of any alcoholic beverage during the run-in period
  4. A detectable serum acetaminophen at baseline
  5. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 50 IU/L at the start of the run-in period or at baseline
  6. Platelet count less than 125,000/cc at baseline
  7. Positive pregnancy test at baseline (female participants only)
  8. Currently adheres to a fasting type diet as determined by self report
  9. Currently has anorexia nervosa as determined by self report
  10. Subject appears clinically intoxicated, psychiatrically impaired or unable to give informed consent for any reason
  11. Known hypersensitivity to acetaminophen
  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: NCT00616018

Locations
United States, Colorado
Denver Health Rocky Mountain Poison and Drug Center
Denver, Colorado, United States, 80204
Sponsors and Collaborators
Kennon Heard
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Investigators
Principal Investigator: Kennon Heard, MD Denver Health/Rocky Mountain Poison & Drug Center
  More Information

No publications provided

Responsible Party: Kennon Heard, Medical Toxicology Fellowship Director, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier: NCT00616018     History of Changes
Other Study ID Numbers: COMIRB #06-1187, COMIRB #06-1187
Study First Received: February 4, 2008
Results First Received: March 3, 2011
Last Updated: July 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Denver Health and Hospital Authority:
acetaminophen
protein adducts
hepatic function
drug safety
non drinkers

Additional relevant MeSH terms:
Drug-Induced Liver Injury
Wounds and Injuries
Liver Diseases
Digestive System Diseases
Poisoning
Substance-Related Disorders
Acetaminophen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014