Acetaminophen MetabolismNCT01246713
Effect on Acetaminophen Metabolism by Liquid Formulations
A study testing Acetaminophen liquid formulation and Acetaminophen solid formulation in people with Acetaminophen Metabolism and Acetaminophen Poisoning, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Acetaminophen Metabolism, Acetaminophen Poisoning, Drug Metabolism by Excipients
- What is being tested?
- Acetaminophen liquid formulation and Acetaminophen solid formulation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Jul 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteer ages 18-40
- Not taking any chronic medications
Who cannot join
- Pregnancy
- Any history of liver disease
- Frequent alcohol use (2 or more drinks more than 4 times per week)
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Harvard - Thorndike Clinical Research Center at Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Effect on Acetaminophen Metabolism by Liquid Formulations: Do Excipients in Liquid Formulation Prevent Production of Toxic Metabolites?
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.
Read the detailed 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.
- Being tested
- Acetaminophen liquid formulation, Acetaminophen solid formulation
- Keywords
- acetaminophen, excipients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetaminophen liquid formulationDrug
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
Acetaminophen solid formulationDrug
Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen solid formulation | Placebo comparator | Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation. Receives: Drug: Acetaminophen solid formulation |
| Acetaminophen liquid formulation | Active comparator | Subjects in this arm will receive a 15mg/kg dose of a liquid acetaminophen formulation. Receives: Drug: Acetaminophen liquid formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionMay 2011
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acetaminophen MetabolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard University, National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Michael Ganetsky, Beth Israel Deaconess Medical Center
- Investigators
- Michael Ganetsky, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246713
- Sponsor's protocol ID
- 2010P000135
- Other IDs
- UL1RR025758
- Status last verified
- Mar 2017
- First submitted
- 22 Nov 2010
- Last updated
- 8 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ganetsky M, Bohlke M, Pereira L, Williams D, LeDuc B, Guatam S, Salhanick SD. Effect of excipients on acetaminophen metabolism and its implications for prevention of liver injury. J Clin Pharmacol. 2013 Apr;53(4):413-20. doi: 10.1002/jcph.24. Epub 2013 Feb 22.
PubMed 23436315
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect on Acetaminophen Metabolism by Liquid Formulations: Do Excipients in Liquid Formulation Prevent Production of Toxic Metabolites?
- ClinicalTrials.gov ID
- NCT01246713
- Acronym / sponsor ID
- 2010P000135
- Keywords
- acetaminophen, excipients
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- Harvard University, National Center for Research Resources (NCRR)
- Study start
- Dec 2010
- Primary completion
- May 2011 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 23 Nov 2010 (estimated)
- Results
- Posted 8 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen solid formulation | Placebo comparator | Drug: Acetaminophen solid formulationSubjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation. |
| Acetaminophen liquid formulation | Active comparator | Drug: Acetaminophen liquid formulationSubjects in this arm will receive a 15mg/kg dose of a liquid acetaminophen formulation. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy volunteer ages 18-40
- Not taking any chronic medications
Key exclusion criteria (4 listed)
- Pregnancy
- Any history of liver disease
- Frequent alcohol use (2 or more drinks more than 4 times per week)
- Unable to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetaminophen liquid formulationSubjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation. | Drug | Acetaminophen liquid formulation |
| Acetaminophen solid formulationSubjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation. | Drug | Acetaminophen solid formulation |
Primary outcome
Acetaminophen Metabolites
Time frame: 8 hours
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23436315Ganetsky M, Bohlke M, Pereira L, Williams D, LeDuc B, Guatam S, Salhanick SD. Effect of excipients on acetaminophen metabolism and its implications for prevention of liver injury. J Clin Pharmacol. 2013 Apr;53(4):413-20. doi: 10.1002/jcph.24. Epub 2013 Feb 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Ganetsky, MD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetaminophen liquid formulation and Acetaminophen solid formulation in people with Acetaminophen Metabolism and Acetaminophen Poisoning, run by Beth Israel Deaconess Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acetaminophen Metabolites (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01246713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.