Aminotransferase Trends During Prolonged Acetaminophen Dosing - Full Text View

Sponsor:	Denver Health and Hospital Authority
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:	NCT00743093

Purpose

The objective of this study is to monitor liver function tests (blood levels of an indicator of liver function) of healthy people taking the maximum labeled daily dose of acetaminophen compared to people taking placebo for 16 to 40 days. Those people that continue to have normal liver tests after 16 days will have completed their part of the study. People that develop abnormal liver function tests will continue taking acetaminophen or placebo, and have their liver tests monitored closely for up to an additional 24 days. This is to (1) make sure these tests return to normal and (2) determine when these tests return to normal while still taking acetaminophen or placebo. If at any time the liver tests indicate anything more than a minor increase, you would be immediately told to stop taking the study drug.

Secondary objective is to determine the proportion of subjects that have detectable acetaminophen-protein adducts after daily dosing.

Condition	Intervention	Phase
Drug Toxicity Healthy	Drug: acetaminophen Drug: placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title:	Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing

Resource links provided by NLM:

Drug Information available for: Acetaminophen CT 2584

U.S. FDA Resources

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

Primary Outcome Measures:

alanine aminotransferase (ALT) [ Time Frame: serial samples over 17-42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

acetaminophen-protein adducts [ Time Frame: serial samples for 16-42 days ] [ Designated as safety issue: Yes ]

Enrollment:	398
Study Start Date:	August 2008
Study Completion Date:	August 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 acetaminophen	Drug: acetaminophen 500 mg caplets; 2 capsules (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days. Other Name: tylenol
Placebo Comparator: 2 placebo	Drug: placebo placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days Other Name: placebo

Detailed Description:

Acetaminophen use is common and many consumers take 4g/day for longer than 4 days. The use of 4g/day of acetaminophen for more than 4 days causes an asymptomatic ALT elevation in some people. This elevation most likely resolves while continuing treatment, but it is possible that some individuals may go on to develop clinical liver injury. By carefully following healthy subjects who are taking the maximal daily dose of acetaminophen, we can safely determine if the ALT elevation resolves or progresses to clinical liver injury. If a subject develops clinical liver injury we can intervene before irreversible injury occurs.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

age 18 or older

Exclusion Criteria:

History of acetaminophen ingestion on any of the four days preceding study enrollment
Measurable serum acetaminophen level at time of enrollment
Viral markers of Hepatitis B or C, or viral markers of Hepatitis A with an ALT level greater than ULN during screening laboratory testing
Serum ALT or AST level greater than ULN at Screening or Day 0
Total bilirubin level greater than ULN at Screening or Day 0
INR level greater than ULN at Screening
Alkaline phosphatase level greater than ULN at Screening
Platelet count less than 125 10^9/L at Screening
Known cholelithiasis
Positive pregnancy test at Screening (female participants only)
History of consuming more than an average of 3 alcohol containing drinks daily over the preceding 2 weeks
History of consuming 3 or more alcohol containing drinks on any given day during the 2 weeks prior to study enrollment
New prescription medication started within the previous 30 days
Currently taking isoniazid
Currently taking warfarin
Currently adheres to a fasting type diet as determined by self report
Currently has anorexia nervosa as determined by self report
Participant is clinically intoxicated, psychiatrically impaired or unable to give informed consent for any reason
Known hypersensitivity or allergy to acetaminophen

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00743093

Locations

United States, Colorado
University of Colorado Health Sciences Center - GCRC
Aurora, Colorado, United States, 80045
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

Publications:

Case JP, Baliunas AJ, Block JA. Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Arch Intern Med. 2003 Jan 27;163(2):169-78.

Davern TJ 2nd, James LP, Hinson JA, Polson J, Larson AM, Fontana RJ, Lalani E, Munoz S, Shakil AO, Lee WM; Acute Liver Failure Study Group. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology. 2006 Mar;130(3):687-94. Erratum in: Gastroenterology. 2006 May;130(6):1933.

García Rodríguez LA, González-Pérez A. Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. BMC Med. 2005 Nov 29;3:17.

Golden HE, Moskowitz RW, Minic M. Analgesic efficacy and safety of nonprescription doses of naproxen sodium compared with acetaminophen in the treatment of osteoarthritis of the knee. Am J Ther. 2004 Mar-Apr;11(2):85-94.

Responsible Party:	Kennon Heard, Fellowship Director, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier:	NCT00743093 History of Changes
Other Study ID Numbers:	COMIRB #06-1265
Study First Received:	August 26, 2008
Last Updated:	August 31, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Denver Health and Hospital Authority:

acetaminophen
protein adducts
drug safety
alanine aminotransferase
Alanine Amino Transferase

Additional relevant MeSH terms:

Drug Toxicity
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 February 09, 2012