- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00493311
Safety of Intravenous Acetaminophen Vs Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
October 18, 2016 updated by: Mallinckrodt
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Single-Dose Study of the Efficacy and Safety of Intravenous Acetaminophen Versus Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
A research study to determine if acetaminophen (APAP) given intravenously (IV-a liquid given through a needle into a vein in your arm) is safe and effective in controlling fever when compared to placebo.
Acetaminophen given this way is the investigational part of this study.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Single-Dose Study of the Efficacy and Safety of Intravenous Acetaminophen (IVAPAP) Versus Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
Study Type
Interventional
Enrollment (Actual)
60
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Austin, Texas, United States, 78705
- Scirex Research Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Provide written Informed Consent prior to participation in the Study
- Be a healthy male between the ages of 18 and 75 years of age, inclusive, at Randomization
- Have a Body Mass Index (BMI) ≥ 19 and ≤ 40 lbs / in2
- Have the ability to read and understand the Study procedures and have the ability to communicate meaningfully with the Study Investigator and staff
- Be free of physical, mental, or medical conditions which, in the opinion of the Investigator, may confound quantifying assessments for the Study
- Be willing to abstain from smoking cigarettes or using nicotine products from the time of admission to Clinic until Study Completion
Inclusion Criteria (Pre-Randomization) To be eligible for entry into the Study, Subjects must meet each of the following criteria prior to Randomization:
- Be free of evidence of infection based upon clinical assessment and blood (Complete Blood Count-CBC) and urine testing
- Have an average baseline oral temperature that is equal to or below 37 ºC (98.6 ºF) and does not vary more than 0.4 ºC (0.7 ºF) from lowest to highest on three assessments performed during a 30 minute period
- Not develop a medically significant allergic or exaggerated systemic response to administration of a test dose of reference standard endotoxin
- Develop a core temperature of at least 38.6 ºC (101.5 ºF) after intravenous reference standard endotoxin dosed per Study guidelines and have a fever response to endotoxin that is at or near the peak temperature by virtue of two consecutive temperature assessments 5 minutes apart that are within 0.2 ºC (0.4 ºF) of each other
Exclusion Criteria:
- Has been treated with any medication having antipyretic effects (e.g., corticosteroid, Non-steroidal anti-inflammatory drug (NSAID), aspirin or acetaminophen) within 2 days of clinic admission (aspirin at low dose for cardiac prophylaxis is allowed, but should not be taken on the day of the Study)
- Has significant medical disease(s), laboratory abnormalities, or condition(s) that in the Investigator's judgment could compromise the Subject's welfare, ability to communicate with the Study staff, complete Study activities, or would otherwise contraindicate Study participation.
- Has known hypersensitivity or contraindication to receiving endotoxin that in the Investigator's clinical judgment merits discontinuation from further Study participation
- Has known hypersensitivity to acetaminophen, the inactive ingredients (excipients) of the Intravenous(IV) acetaminophen formulation or the Rescue Medications (ibuprofen, aspirin and ketorolac)
- Has known or suspected recent history of alcohol or drug abuse or dependence as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria
- Has a history of nasal polyps, angioedema, significant or actively treated bronchospastic disease, or any other significant medical condition that contraindicates participation in the Study or receiving endotoxin, Study Medication, or Rescue Medication
- Has an active infection or other disease or condition that may cause abnormal alterations in body temperature, or has worked the night shift on a regular basis for the last 3 months prior to Screening
- Has impaired liver function, e.g. Alanine aminotransferases (ALT) greater than or equal to 3 times the upper limit of normal, bilirubin greater than 3.0, active hepatic disease, or evidence of clinically significant liver disease (e.g., cirrhosis or hepatitis)
- Has participated in another clinical Study (investigational or marketed product) within 30 days of Screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IV Acetaminophen
1 g of acetaminophen in 100 mL of intravenous solution
|
Intravenous acetaminophen solution 1 g / 100 ml
Other Names:
Administration of Reference Standard Endotoxin (RSE) to induce fever.
Applicable to both study arms: Administration of a 1 ng/kg body weight test dose of RSE to test for fever response.
Observation period of at least 60 minutes to ensure no exaggerated systemic responses, followed by administration of a 4 ng/kg of RSE to induce fever.
Other Names:
|
Placebo Comparator: IV Placebo
100 mL of intravenous placebo solution
|
Administration of Reference Standard Endotoxin (RSE) to induce fever.
Applicable to both study arms: Administration of a 1 ng/kg body weight test dose of RSE to test for fever response.
Observation period of at least 60 minutes to ensure no exaggerated systemic responses, followed by administration of a 4 ng/kg of RSE to induce fever.
Other Names:
IV Placebo
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Weighted Sum of Temperature Differences Over 6 Hours (WSTD6) Assessment of the Antipyretic Effect Over 6 h of a Single Dose of IV APAP vs. Placebo for Treatment of Endotoxin-induced Fever
Time Frame: Baseline (T0) to 6 hours post study drug administration
|
The primary efficacy endpoint was WSTD6 defined as the weighted sum of temperature differences from the temperature at each assessment timepoint through 6 hours compared with the temperature at T0, weighted by the time elapsed between each 2 consecutive timepoints.
|
Baseline (T0) to 6 hours post study drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Weighted Sum of Temperature Differences Over 3 Hours (WSTD3) Assessment of the Antipyretic Effect Over 3 Hours of a Single Dose of IV APAP vs. Placebo for Treatment of Endotoxin-induced Fever.
Time Frame: Baseline (T0) to 3 hours
|
WSTD3 is defined as the weighted sum of temperature differences from the temperature at each assessment timepoint through the first 3 hours compared with the temperature at T0, weighted by the time elapsed between each 2 consecutive timepoints.
|
Baseline (T0) to 3 hours
|
Maximum Temperature Change During the Period From T0 to T360 Minutes (6 Hours After Study Drug Administration)
Time Frame: Baseline (T0) to 360 minutes (6 hours) post study drug administration
|
Baseline (T0) to 360 minutes (6 hours) post study drug administration
|
|
The Percentage of Subjects With Temperature Less Than 38 Degrees Celsius at Any Timepoint During the Time From T0 to T360 Minutes (6 Hours After Study Drug Administration)
Time Frame: 360 minutes (6 hours after study drug administration)
|
360 minutes (6 hours after study drug administration)
|
|
Global Assessment of Treatment at T360 Minutes or Early Termination.
Time Frame: Baseline (T0) to 6 hours
|
Subject Global Evaluation was assessed by subject using a 4 point categorical scale in response to the following question:Overall, how would you rate the study treatments? 0 = Poor
|
Baseline (T0) to 6 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2007
Primary Completion (Actual)
October 1, 2007
Study Completion (Actual)
October 1, 2007
Study Registration Dates
First Submitted
June 27, 2007
First Submitted That Met QC Criteria
June 27, 2007
First Posted (Estimate)
June 28, 2007
Study Record Updates
Last Update Posted (Estimate)
October 19, 2016
Last Update Submitted That Met QC Criteria
October 18, 2016
Last Verified
October 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CPI-APF-302
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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