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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing|
- 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 ] [ Designated as safety issue: Yes ]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.
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2008|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
acetaminophen, 4 grams/day (1 gram every 4 hours for 4 doses)
500 mg caplets; 2 caplets (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days.
Other Name: tylenol
Placebo Comparator: placebo
placebo for acetaminophen 4 grams/day (2 caplets every 4 hours for 4 doses)
placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days
Other Name: placebo
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.
|United States, Colorado|
|University of Colorado Health Sciences Center - GCRC|
|Aurora, Colorado, United States, 80045|
|Denver Health Rocky Mountain Poison and Drug Center|
|Denver, Colorado, United States, 80204|
|Principal Investigator:||Kennon Heard, MD||Denver Health/Rocky Mountain Poison & Drug Center|