FeverPhase 3NCT00564629

Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males

A Phase 3 study testing Reference standard endotoxin (RSE) in people with Fever, run by Mallinckrodt at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 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?: Reference standard endotoxin (RSE)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 105 participants
Where: 1 siteUnited States
Study dates: Aug 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

None listed.

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) 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

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

New Orleans Center for Clinical Research-Knoxville
Knoxville, Tennessee, 37920

Other trials in United States

About this study

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

Read the 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

Conditions: Fever
Being tested: Intravenous acetaminophen plus oral placebo, Oral acetaminophen plus IV placebo, 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.

Intravenous acetaminophen plus oral placeboDrug
Also called IV APAP
Single dose of 1 gm IV acetaminophen
Oral acetaminophen plus IV placeboDrug
Also called IV APAP
Single dose of 1 g PO APAP
Reference standard endotoxin (RSE)Biological
Also called RSE
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.

Study groups in NCT00564629
Study group	Role	What they receive
IV acetaminophen plus oral placebo.	Experimental	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. Receives: Drug: Intravenous acetaminophen plus oral placebo; Biological: Reference standard endotoxin (RSE)
Oral acetaminophen plus IV placebo.	Active comparator	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. Receives: Drug: Oral acetaminophen plus IV placebo; Biological: Reference standard endotoxin (RSE)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 0-2 hours

Secondary outcomes (8)

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.
Measured: 6 hours
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.
Measured: T0-T360 minutes
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).
Measured: T360 minutes
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.
Measured: 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.
Measured: 0-3 hours
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.
Measured: 0-4 hours
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.
Measured: 0-5 hours
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.
Measured: 0-6 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2007Oct 2007

First posted28 Nov 2007 (estimated)
Study startAug 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: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 105 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00564629
Sponsor's protocol ID: CPI-APF-303
Status last verified: Oct 2016
First submitted: 26 Nov 2007
Last updated: 19 Oct 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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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, 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
ClinicalTrials.gov ID: NCT00564629
Acronym / sponsor ID: CPI-APF-303
Conditions: Fever
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 105 participants (actual)
Lead sponsor: MallinckrodtIndustry (pharma, biotech, devices)
Study start: Aug 2007
Primary completion: Oct 2007 (actual)
Study completion: Oct 2007 (actual)
First posted: 28 Nov 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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
IV acetaminophen plus oral placebo.	Experimental	Drug: Intravenous acetaminophen plus oral placebo, Biological: Reference standard endotoxin (RSE)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.
Oral acetaminophen plus IV placebo.	Active comparator	Drug: Oral acetaminophen plus IV placebo, Biological: Reference standard endotoxin (RSE)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.

Who may qualify

Ages: 18 to 75 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

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) 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

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
Intravenous acetaminophen plus oral placeboAlso: IV APAPSingle dose of 1 gm IV acetaminophen	Drug	IV acetaminophen plus oral placebo.
Oral acetaminophen plus IV placeboAlso: IV APAPSingle dose of 1 g PO APAP	Drug	Oral acetaminophen plus IV placebo.
Reference standard endotoxin (RSE)Also: RSETo 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.	Biological	IV acetaminophen plus oral placebo., Oral acetaminophen plus IV placebo.

Primary outcome

The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)
Time frame: 0-2 hours
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.

8 secondary outcomes

Time to a Reduction in Temperature From T0 to T360 Minutes.
Time frame: 6 hours
Maximum Temperature Reduction Observed From T0 to T360 Minutes
Time frame: T0-T360 minutes
Subject's Global Evaluation of Study Medication at T360 Minutes
Time frame: T360 minutes
The Percentage of Subjects With Temperature < 38 ºC and < 38.5 ºC at Any Timepoint During the Time From T0 to T360 Minutes
Time frame: T0 to T360 minutes
WSTD3
Time frame: 0-3 hours
WSTD4
Time frame: 0-4 hours
WSTD5
Time frame: 0-5 hours
WSTD6
Time frame: 0-6 hours

Results and safety

Results posted to the registry on 21 Sep 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Oral Acetaminophen (PO APAP) 1 g	51	36
Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution	54	45

Primary outcome: The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2)

Time frame: 0-2 hours. Mean (Standard Deviation). Unit: Degrees Celsius

Measure	IV APAP 1 g / 100 ml Solution n = 45	PO APAP 1 g n = 36
Value	0.3 (0.41)	0.6 (0.55)

Population analysed: mITT population defined as all randomized subjects who received at least 1 full dose of oral study medication (subject not vomiting within 2 hours after oral study drug) or 1 full dose of IV study medication(subject having received all 100 mls solution). This analysis was performed with imputation for non-physiological temperature swing zone effect

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Oral Acetaminophen (PO APAP) 1 g	0 of 51 (0%)	17 of 51 (33.3%)	Not reported
Intravenous Acetaminophen (IV APAP) 1 g / 100 ml Solution	0 of 54 (0%)	13 of 54 (24.1%)	Not reported

Limitations and caveats (from the sponsor): Protocol and statistical analysis plan were amended to clarify endpoints prior to database lock and analysis.

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.

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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.

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 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 0 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. 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?

The Rapidity of Onset of Antipyretic Effect at 2 Hours (Measured as Weighted Sum of Temperature Differences Over 2 Hours, WSTD2) (time frame: 0-2 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 NCT00564629.

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.