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

Drug Induced Liver Injury Clinical Trial

— Non-Drinker  

Official title:

Acetaminophen Adduct Formation in Alcohol Abstaining Subjects Administered Therapeutic Doses of Acetaminophen for Ten Consecutive Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00616018
• Other study ID #: COMIRB #06-1187
• Secondary ID: COMIRB #06-1187
• Status: Completed
• Phase: Phase 4
• First received: February 4, 2008
• Last updated: July 10, 2012
• Start date: August 2007
• Est. completion date: January 2008

Study information

• Verified date: July 2012
• Source: Denver Health and Hospital Authority
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Drug Induced Liver Injury
• Drug-Induced Liver Injury

Intervention

Drug:
• acetaminophen
4 g/day for 10 consecutive days

Locations

Country	Name	City	State
United States	Denver Health Rocky Mountain Poison and Drug Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Kennon Heard	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	Alanine Aminotransferase (ALT)	ALT was measured at Day 0, 4, 7, 9, 11, and 14.	Day 0, 4, 7, 9, 11, and 14.	Yes