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Completed

NCT Number: NCT00743093

Aminotransferase Trends During Prolonged Acetaminophen Dosing

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.

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Key information

Conditions

Drug Toxicity Chemically-Induced Disorders Drug-Related Side Effects and Adverse Reactions Healthy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Acetaminophen

Drug

500 mg caplets; 2 caplets (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days.

Other names: tylenol

Placebo

Drug

placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days

Primary outcomes

  1. The Proportion of Subjects Treated With Long-term Acetaminophen (4 g/Day) That Develops Persistent ALT Elevations.

    Time frame: serial samples for 16-40 days

    ALT was measured on Day 0 and 16 for all study participants. Subjects with an elevated ALT at Day 16 continued dosing with study drug and continued to have their ALT measured every three days until the ALT elevation resolved or until Day 40. Persistent ALT elevation was defined as any subject with an unresolved ALT elevation at study Day 40.

Secondary outcomes

  1. The Proportion of Subjects With Detectable Serum Acetaminophen-cysteine Adduct (APAP-cys) Concentrations 1, 2, and 3 Days After Starting the Maximal Recommended Dosing of Acetaminophen (4 g/Day).

    Time frame: Days 1-3

Sponsors and collaborators

Lead sponsor

Denver Health and Hospital Authority

Other

Collaborators

  • McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Registry information

Official study title

Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Aug 28, 2008
Registry last updated
Sep 18, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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