FeverPhase 3NCT00493311
Safety of Intravenous Acetaminophen Vs Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
A Phase 3 study testing IV Acetaminophen and Reference Standard Endotoxin (RSE) in people with Fever, run by Mallinckrodt at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Fever
- What is being tested?
- IV Acetaminophen and Reference Standard Endotoxin (RSE)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Oct 2007
- Phase
- Phase 3
- 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 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Conditions
- Fever
- Being tested
- IV Placebo, IV Acetaminophen, Reference Standard Endotoxin (RSE)
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV PlaceboDrug
Also called Placebo
IV Placebo
IV AcetaminophenDrug
Also called IV APAP, APAP
Intravenous acetaminophen solution 1 g / 100 ml
Reference Standard Endotoxin (RSE)Biological
Also called IV Acetaminophen, APAP
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.
| Study group | Role | What they receive |
|---|---|---|
| IV Acetaminophen | Experimental | 1 g of acetaminophen in 100 mL of intravenous solution Receives: Drug: IV Acetaminophen; Biological: Reference Standard Endotoxin (RSE) |
| IV Placebo | Placebo comparator | 100 mL of intravenous placebo solution Receives: Drug: IV Placebo; Biological: Reference Standard Endotoxin (RSE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: Baseline (T0) to 6 hours post study drug administration
Secondary outcomes (4)
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.
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.
Measured: Baseline (T0) to 3 hours
Maximum Temperature Change During the Period From T0 to T360 Minutes (6 Hours After Study Drug Administration)
Measured: 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)
Measured: 360 minutes (6 hours after study drug administration)
Global Assessment of Treatment at T360 Minutes or Early Termination.
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
- = Fair
- = Good
- = Excellent
Measured: Baseline (T0) to 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2007 (estimated)
- Study startJun 2007
- Primary completionOct 2007
- Study completionOct 2007
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.
- Other trials for FeverStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00493311
- Sponsor's protocol ID
- CPI-APF-302
- Status last verified
- Oct 2016
- First submitted
- 27 Jun 2007
- Last updated
- 19 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00493311
- Acronym / sponsor ID
- CPI-APF-302
- Conditions
- Fever
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 28 Jun 2007 (estimated)
- Results
- Posted 21 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Acetaminophen | Experimental | Drug: IV Acetaminophen, Biological: Reference Standard Endotoxin (RSE)1 g of acetaminophen in 100 mL of intravenous solution |
| IV Placebo | Placebo comparator | Drug: IV Placebo, Biological: Reference Standard Endotoxin (RSE)100 mL of intravenous placebo solution |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| IV PlaceboAlso: PlaceboIV Placebo | Drug | IV Placebo |
| IV AcetaminophenAlso: IV APAP, APAPIntravenous acetaminophen solution 1 g / 100 ml | Drug | IV Acetaminophen |
| Reference Standard Endotoxin (RSE)Also: IV Acetaminophen, APAPAdministration 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. | Biological | IV Acetaminophen, IV Placebo |
Primary outcome
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.
4 secondary outcomes
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
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
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)
Global Assessment of Treatment at T360 Minutes or Early Termination.
Time frame: Baseline (T0) to 6 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Fever
Recruiting
Assessment of Communication Interventions on Vaccination Knowledge and Acceptance
Vaccination Knowledge and Acceptance, Informed Vaccine-decision Making
RecruitingObservational study
Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders
Trisomy 8 Mosaicism, Trisomy 8 Associated Autoinflammatory Disease
RecruitingObservational study
Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
Familial Mediterranean Fever (FMF), Autoinflammation
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
Recruiting
Recovery After Fatigue in Young Athletes: Comparison Between TECAR Therapy and Cycle Ergometer"
Muscle Fatigue, Healthy Adult
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IV Acetaminophen and Reference Standard Endotoxin (RSE) in people with Fever, run by Mallinckrodt 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 11 inclusion and 9 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 19 Oct 2016. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2010). 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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2016.