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

This study has been completed.

First Received on February 4, 2008. Last Updated on February 6, 2009 History of Changes

Sponsor:	Denver Health and Hospital Authority
Collaborator:	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by:	Denver Health and Hospital Authority
ClinicalTrials.gov Identifier:	NCT00616018

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:

Drug Information available for: Acetaminophen

U.S. FDA Resources

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

Primary Outcome Measures:

serum level of APAP-Cys protein adducts [ Time Frame: before, during and following 10 days of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

alanine aminotransferase (ALT) [ Time Frame: before, during and following 10 days of therapy ] [ Designated as safety issue: Yes ]

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 acetaminophen 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:

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

Exclusion Criteria:

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

Contacts and Locations

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

Denver Health and Hospital Authority

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, MD/Medical Toxicology Fellowship Director, Denver Health/Rocky Mountain Poison and Drug Center
ClinicalTrials.gov Identifier:	NCT00616018 History of Changes
Other Study ID Numbers:	COMIRB #06-1187, COMIRB #06-1187
Study First Received:	February 4, 2008
Last Updated:	February 6, 2009
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
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 May 22, 2012