Back to resultsStudy of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males
Primary Purpose
Fever
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Intravenous acetaminophen plus oral placebo
Oral acetaminophen plus IV placebo
Reference standard endotoxin (RSE)
Sponsored by
About this trial
This is an interventional treatment trial for Fever
Eligibility Criteria
Inclusion Criteria (Screening) To be eligible for entry into the Study, Subjects must meet all of the following criteria at Screening:
- 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 ≤ 45 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 Randomization, Subjects must meet each of the following criteria:
- 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 IV 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) or oral (PO) 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 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
- Has impaired liver function, e.g.Alanine aminotransferase (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
Sites / Locations
- New Orleans Center for Clinical Research-Knoxville
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IV acetaminophen plus oral placebo.
Oral acetaminophen plus IV placebo.
Arm Description
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. Randomization to receive 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo.
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. Randomization to receive oral acetaminophen 1 g plus 100 ml of intravenous placebo solution.
Outcomes
Primary Outcome Measures
The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)
This outcome measures when the antipyretic effect begins by statistical analysis of WSTD2, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 2 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Secondary Outcome Measures
Time to a Reduction in Temperature From T0 to T360 Minutes.
This outcome measures how much time it took to observe a decrease in subjects' core body temperature by 0.8 ºC, 1.0 ºC, and 1.5 ºC from the temperature at T0 and from the temperature at the peak after T0 through T360 (6 hours). The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Maximum Temperature Reduction Observed From T0 to T360 Minutes
This outcome measures the maximum core temperature reduction observed from T0 to T360 minutes. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Subject's Global Evaluation of Study Medication at T360 Minutes
This outcome measures how satisfied the subject was with the study treatment. The subject was asked to answer "Overall, how would you rate study treatments?" at T360 minutes using a 4-point categorical scale (0=poor, 1=fair, 2=good, 3=excellent).
The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes
This outcome measures what percentage of total subjects had a temperature < 38 ºC and < 38.5 ºC at any timepoint during the time from T0 to T360 minutes.
WSTD3
This outcome measure is a statistical analysis of WSTD3, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 3 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
WSTD4
This outcome measure is a statistical analysis of WSTD4, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 4 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
WSTD5
This outcome measure is a statistical analysis of WSTD5, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 5 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
WSTD6
This outcome measure is a statistical analysis of WSTD6, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 6 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00564629
Brief Title
Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males
Official Title
A Phase III, Randomized, Double-Blind, Double-Dummy, Single-Dose Study of the Efficacy and Safety of Intravenous Acetaminophen Versus Oral Acetaminophen for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To assess the rapidity of onset of antipyretic effect and the efficacy and safety of a single dose of IV acetaminophen (IV APAP) versus oral (PO) acetaminophen in the treatment of fever induced by a standard dose of endotoxin
Detailed Description
A Phase III, Randomized, Double-Blind, Double-Dummy, Single-Dose Study of the Efficacy and Safety of Intravenous Acetaminophen Versus Oral Acetaminophen for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fever
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
105 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IV acetaminophen plus oral placebo.
Arm Type
Experimental
Arm Description
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. Randomization to receive 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo.
Arm Title
Oral acetaminophen plus IV placebo.
Arm Type
Active Comparator
Arm Description
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. Randomization to receive oral acetaminophen 1 g plus 100 ml of intravenous placebo solution.
Intervention Type
Drug
Intervention Name(s)
Intravenous acetaminophen plus oral placebo
Other Intervention Name(s)
IV APAP
Intervention Description
Single dose of 1 gm IV acetaminophen
Intervention Type
Drug
Intervention Name(s)
Oral acetaminophen plus IV placebo
Other Intervention Name(s)
IV APAP
Intervention Description
Single dose of 1 g PO APAP
Intervention Type
Biological
Intervention Name(s)
Reference standard endotoxin (RSE)
Other Intervention Name(s)
RSE
Intervention Description
To subjects in both study arms: Administration of a 1 ng/kg body weight test dose of RSE to induce fever and 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.
Primary Outcome Measure Information:
Title
The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)
Description
This outcome measures when the antipyretic effect begins by statistical analysis of WSTD2, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 2 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
0-2 hours
Secondary Outcome Measure Information:
Title
Time to a Reduction in Temperature From T0 to T360 Minutes.
Description
This outcome measures how much time it took to observe a decrease in subjects' core body temperature by 0.8 ºC, 1.0 ºC, and 1.5 ºC from the temperature at T0 and from the temperature at the peak after T0 through T360 (6 hours). The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
6 hours
Title
Maximum Temperature Reduction Observed From T0 to T360 Minutes
Description
This outcome measures the maximum core temperature reduction observed from T0 to T360 minutes. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
T0-T360 minutes
Title
Subject's Global Evaluation of Study Medication at T360 Minutes
Description
This outcome measures how satisfied the subject was with the study treatment. The subject was asked to answer "Overall, how would you rate study treatments?" at T360 minutes using a 4-point categorical scale (0=poor, 1=fair, 2=good, 3=excellent).
Time Frame
T360 minutes
Title
The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes
Description
This outcome measures what percentage of total subjects had a temperature < 38 ºC and < 38.5 ºC at any timepoint during the time from T0 to T360 minutes.
Time Frame
T0 to T360 minutes
Title
WSTD3
Description
This outcome measure is a statistical analysis of WSTD3, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 3 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
0-3 hours
Title
WSTD4
Description
This outcome measure is a statistical analysis of WSTD4, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 4 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
0-4 hours
Title
WSTD5
Description
This outcome measure is a statistical analysis of WSTD5, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 5 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
0-5 hours
Title
WSTD6
Description
This outcome measure is a statistical analysis of WSTD6, which is the weighted sum of temperature differences from the subject's core temperature at each assessment time point through the first 6 hours compared with the subject's core temperature at T0, weighted by the time elapsed between each 2 consecutive time points. The subject's core temperature was measured using an ingestible temperature monitoring capsule and associated data recorder.
Time Frame
0-6 hours
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (Screening) To be eligible for entry into the Study, Subjects must meet all of the following criteria at Screening:
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 ≤ 45 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 Randomization, Subjects must meet each of the following criteria:
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 IV 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) or oral (PO) 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 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
Has impaired liver function, e.g.Alanine aminotransferase (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
Facility Information:
Facility Name
New Orleans Center for Clinical Research-Knoxville
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males
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