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Aminotransferase Trends During Prolonged Acetaminophen Dosing

This study has been completed.
Sponsor:
Collaborator:
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by (Responsible Party):
Kennon Heard, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier:
NCT00743093
First received: August 26, 2008
Last updated: September 6, 2013
Last verified: September 2013
History of Changes
Results First Received: March 18, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Conditions: Drug Toxicity
Healthy
Interventions: Drug: acetaminophen
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment took place from August 2008 through August 2011 in the Denver Metro area. Healthy volunteers were recruited from the community through the use of approved advertisements.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
398 subjects were consented for the study. Of these, 122 were excluded for not meeting full eligibility criteria. 276 eligible subjects were assigned to treatment groups, of which 252 completed all study requirements.

Reporting Groups
  Description
Acetaminophen Arm

acetaminophen

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

placebo

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

Participant Flow for 2 periods

 Period 1:   Base Study Period
    Acetaminophen Arm     Placebo Arm  
STARTED     224     52  
COMPLETED     205     47  
NOT COMPLETED     19     5  

Period 2:   Extended Dosing Period
    Acetaminophen Arm     Placebo Arm  
STARTED     51 [1]   1 [1]
COMPLETED     48     1  
NOT COMPLETED     3     0  
[1] Subjects not meeting stopping criteria after base continued into the extended dosing.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline characteristics were collected on all subjects at screening and included: race, ethnicity, gender, age, weight, and height. The number of participants included in the analysis (276) is based on the safety population, which includes any subject that took at least one dose of study medication.

Reporting Groups
  Description
Acetaminophen Arm acetaminophen 500 mg
Placebo Arm placebo
Total Total of all reporting groups

Baseline Measures
    Acetaminophen Arm     Placebo Arm     Total  
Number of Participants  
[units: participants]
 		  224     52     276  
Age  
[units: participants]
 		     
<=18 years     1     0     1  
Between 18 and 65 years     221     52     273  
>=65 years     2     0     2  
Age  
[units: years]
Mean (Standard Deviation) 		  36.3  (12.16)     35.8  (12.50)     36.2  (12.21)  
Gender  
[units: participants]
 		     
Female     163     39     202  
Male     61     13     74  
Region of Enrollment  
[units: participants]
 		     
United States     224     52     276  



  Outcome Measures
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1.  Primary:   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 ]
  Show Outcome Measure 1

2.  Secondary:   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 ]
  Show Outcome Measure 2


  Serious Adverse Events
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  Other Adverse Events
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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This study was limited to healthy volunteers. The ingestion of each dose of study drug and use of other medications was self-reported.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Jody Green, PhD
Organization: Denver Heatlh Rocky Mountain Poison and Drug Center
phone: 303-389-1246
e-mail: jody.green@rmpdc.org


Publications:
Drug Induced Liver Injury Network, U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for Industry Drug Induced Liver Injury: Premarketing Clinical Evaluation [Web Page]. 2007 Oct; Accessed 2008 Jan 17. Available at: http://www.fda.gov/cder/guidance/index.htm.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Kennon Heard, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier: NCT00743093     History of Changes
Other Study ID Numbers: COMIRB #06-1265
Study First Received: August 26, 2008
Results First Received: March 18, 2013
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration