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

NCT00616018 | Completed Phase 4 Results DMC

• 1 other identifier: COMIRB #06-1187
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Induced Liver Injury

Keywords

acetaminophen; protein adducts; hepatic function; drug safety; non drinkers

Outcome Measures

Primary Outcomes (1)

• Serum Level of Acetaminophen-cysteine (APAP-Cys) Protein Adducts

  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.

  Day 0, 4, 7, 9, 11, and 14.

Secondary Outcomes (1)

• Alanine Aminotransferase (ALT)

  Day 0, 4, 7, 9, 11, and 14.

Study Arms (1)

A

EXPERIMENTAL

all subjects receive 4 g/day of acetaminophen for 10 consecutive days in this open-label study

Drug: acetaminophen

Interventions

acetaminophen DRUG

4 g/day for 10 consecutive days

Also known as: Tylenol Extra Strength

A

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of ingesting more than 4 grams of acetaminophen per day for any of the 4 days preceding study enrollment
• Currently taking isoniazid
• Consumption of any alcoholic beverage during the run-in period
• A detectable serum acetaminophen at baseline
• 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
• 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

Sponsors & Collaborators

• Kennon Heard: lead
• McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.: collaborator

Study Sites (1)

Denver Health Rocky Mountain Poison and Drug Center

Denver, Colorado, 80204, United States

Location

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Limitations and Caveats

One limitation is that this study did not include a placebo group. The study was limited to healthy volunteers. The ingestion of each dose and use of other medications was self-reported.

Results Point of Contact

• Title: Jody Green
• Organization: Denver Health

jody.green@rmpdc.org

303-389-1246

Study Officials

• Kennon Heard, MD

  Denver Health/Rocky Mountain Poison & Drug Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Toxicology Fellowship Director

Study Record Dates

• First Submitted: February 4, 2008
• First Posted: February 14, 2008
• Study Start: August 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: July 12, 2012
• Results First Posted: July 12, 2012

Record last verified: 2012-07

Locations

US (1)