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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01246713
Other study ID # 2010P-000135
Secondary ID UL1RR025758
Status Completed
Phase N/A
First received November 22, 2010
Last updated March 26, 2013
Start date December 2010
Est. completion date July 2012

Study information

Verified date March 2013
Source Beth Israel Deaconess Medical Center
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine whether excipients in the liquid formulation of acetaminophen prevent the formation of the toxic metabolites of acetaminophen.


Description:

Acetaminophen (APAP) poisoning is the most frequent cause of acute hepatic failure in the United States. Toxicity requires cytochrome P-450 bioactivation of APAP. Children are less susceptible to APAP toxicity; the current theory is that they have different metabolism than adults. However, children's liquid preparations of APAP contain excipients which have been shown to inhibit APAP bioactivation in vitro and in rodents. Children tend to ingest liquid preparations, which could potentially explain their decreased susceptibility instead of an intrinsically different metabolism. Further, our review of Poison Center epidemiologic data shows that liquid preparations are less toxic in adults. Our hypothesis is that excipients in liquid preparations inhibit the bioactivation of APAP. The design is a pharmacokinetic cross-over study in humans. Healthy adult subjects will be recruited for administration of therapeutic doses of APAP in capsule and liquid formulations. Plasma via a heplock will be collected at serial time points up to 8 hours and assayed for APAP and its metabolites. After a washout period, subjects will receive the same dose of APAP in the alternate preparation. The pattern of metabolites, indicating the activity of the bioactivating enzymes, will be compared. A significant difference in P-450 metabolites will support the hypothesis and provide preliminary data for studies in patients who have ingested potentially toxic doses of APAP. Ultimately, this work could support development of novel antidotal therapy for APAP overdose.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date July 2012
Est. primary completion date May 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 40 Years
Eligibility Inclusion Criteria:

- Healthy volunteer ages 18-40

- Not taking any chronic medications

Exclusion Criteria:

- Pregnancy

- Any history of liver disease

- Frequent alcohol use (2 or more drinks more than 4 times per week)

- Unable to provide informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label


Intervention

Drug:
Acetaminophen liquid formulation
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
Acetaminophen solid formulation
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.

Locations

Country Name City State
United States Harvard - Thorndike Clinical Research Center at Beth Israel Deaconess Medical Center Boston Massachusetts

Sponsors (3)

Lead Sponsor Collaborator
Beth Israel Deaconess Medical Center Harvard University, National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Acetaminophen Metabolites Area-under-curve from time zero to 8 hours for APAP-cysteinate metabolite. Serum was collected just prior to and at hours 1, 2, 4, 6, and 8 after administration of the APAP dose. 8 hours No
See also
  Status Clinical Trial Phase
Recruiting NCT05517668 - Evaluation of the Efficacy of Fomepizole in the Treatment of Acetaminophen Overdose Phase 2