Conditions: Drug Toxicity Healthy
Keywords: acetaminophen protein adducts drug safety alanine aminotransferase Alanine Amino Transferase
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 398
Healthy volunteers: yes

Brief 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.

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.

Arms:
arm 1: acetaminophen, 4 grams/day (1 gram every 4 hours for 4 doses) arm 2: placebo for acetaminophen 4 grams/day (2 caplets every 4 hours for 4 doses)

Interventions: intervention 1: acetaminophen intervention 2: placebo
Intervention descriptions: intervention 1: 500 mg caplets; 2 caplets (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days. intervention 2: placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days

Protocol document: