Aminotransferase Trends During Prolonged Acetaminophen Dosing
Condition: Drug Toxicity; Healthy
MeSH terms: Drug-Related Side Effects and Adverse Reactions
Intervention: acetaminophen; placebo
Intervention description: 500 mg caplets; 2 caplets (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days.; placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days
Intervention MeSH terms: Acetaminophen
Phase: Phase 4
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 398.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: acetaminophen; protein adducts; drug safety; alanine aminotransferase; Alanine Amino Transferase

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  age 18 or older

        Exclusion Criteria:

          1. History of acetaminophen ingestion on any of the four days preceding study enrollment

          2. Measurable serum acetaminophen level at time of enrollment

          3. Viral markers of Hepatitis B or C, or viral markers of Hepatitis A with an ALT level
             greater than ULN during screening laboratory testing

          4. Serum ALT or AST level greater than ULN at Screening or Day 0

          5. Total bilirubin level greater than ULN at Screening or Day 0

          6. INR level greater than ULN at Screening

          7. Alkaline phosphatase level greater than ULN at Screening

          8. Platelet count less than 125 10^9/L at Screening

          9. Known cholelithiasis

         10. Positive pregnancy test at Screening (female participants only)

         11. History of consuming more than an average of 3 alcohol containing drinks daily over
             the preceding 2 weeks

         12. History of consuming 3 or more alcohol containing drinks on any given day during the 2
             weeks prior to study enrollment

         13. New prescription medication started within the previous 30 days

         14. Currently taking isoniazid

         15. Currently taking warfarin

         16. Currently adheres to a fasting type diet as determined by self report

         17. Currently has anorexia nervosa as determined by self report

         18. Participant is clinically intoxicated, psychiatrically impaired or unable to give
             informed consent for any reason

         19. Known hypersensitivity or allergy to acetaminophen