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

Sponsor:	Cadence Pharmaceuticals
Information provided by:	Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00564629

Purpose

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

Condition	Intervention	Phase
Fever	Drug: Intravenous acetaminophen plus oral placebo Drug: Oral acetaminophen plus IV placebo Biological: Reference standard endotoxin (RSE)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Fever

Drug Information available for: Acetaminophen CT 2584

U.S. FDA Resources

Further study details as provided by Cadence Pharmaceuticals:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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. [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: T0-T360 minutes ] [ Designated as safety issue: No ]
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 [ Time Frame: T360 minutes ] [ Designated as safety issue: No ]
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 [ Time Frame: T0 to T360 minutes ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-3 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-4 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-5 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-6 hours ] [ Designated as safety issue: No ]
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.

Enrollment:	105
Study Start Date:	August 2007
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IV acetaminophen plus 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 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo.	Drug: Intravenous acetaminophen plus oral placebo Single dose of 1 gm IV acetaminophen Other Name: IV APAP Biological: Reference standard endotoxin (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. Other Name: RSE
Active Comparator: Oral acetaminophen plus IV 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.	Drug: Oral acetaminophen plus IV placebo Single dose of 1 g PO APAP Other Name: IV APAP Biological: Reference standard endotoxin (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. Other Name: RSE

Arms

Assigned Interventions

Experimental: IV acetaminophen plus 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 1 g of acetaminophen in 100 ml of intravenous solution and oral placebo.

Drug: Intravenous acetaminophen plus oral placebo

Single dose of 1 gm IV acetaminophen

Other Name: IV APAP

Biological: Reference standard endotoxin (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.

Other Name: RSE

Active Comparator: Oral acetaminophen plus IV 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.

Drug: Oral acetaminophen plus IV placebo

Single dose of 1 g PO APAP

Other Name: IV APAP

Biological: Reference standard endotoxin (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.

Other Name: RSE

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

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00564629

Locations

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

Sponsors and Collaborators

Cadence Pharmaceuticals

Investigators

Study Director:

Mike Royal, MD, JD, MBA

Cadence Pharmaceuticals

More Information

No publications provided

Responsible Party:	Mike Royal MD JD MBA, VP Clinical Development, Analgesics, Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00564629 History of Changes
Other Study ID Numbers:	CPI-APF-303
Study First Received:	November 26, 2007
Results First Received:	September 25, 2009
Last Updated:	November 12, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Fever
Body Temperature Changes
Signs and Symptoms
Acetaminophen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions

Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012