Safety of Intravenous Acetaminophen Vs Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males - Full Text View

Sponsor:	Cadence Pharmaceuticals
Information provided by:	Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00493311

Purpose

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.

Condition	Intervention	Phase
Fever	Drug: IV Placebo Drug: IV Acetaminophen 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, Outcomes Assessor) Primary Purpose: Treatment
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

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:

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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
Global Assessment of Treatment at T360 Minutes or Early Termination. [ Time Frame: Baseline (T0) to 6 hours ] [ Designated as safety issue: No ]
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
1. = Fair
2. = Good
3. = Excellent

Enrollment:	60
Study Start Date:	June 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 1 g of acetaminophen in 100 mL of intravenous solution	Drug: IV Acetaminophen Intravenous acetaminophen solution 1 g / 100 ml Other Names: IV APAP APAP Biological: Reference Standard Endotoxin (RSE) 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 Acetaminophen APAP
Placebo Comparator: IV Placebo 100 mL of intravenous placebo solution	Drug: IV Placebo IV Placebo Other Name: Placebo Biological: Reference Standard Endotoxin (RSE) 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 Acetaminophen APAP

Arms

Assigned Interventions

Experimental: IV Acetaminophen

1 g of acetaminophen in 100 mL of intravenous solution

Drug: IV Acetaminophen

Intravenous acetaminophen solution 1 g / 100 ml

Other Names:

IV APAP
APAP

Biological: Reference Standard Endotoxin (RSE)

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 Acetaminophen
APAP

Placebo Comparator: IV Placebo

100 mL of intravenous placebo solution

Drug: IV Placebo

IV Placebo

Other Name: Placebo

Biological: Reference Standard Endotoxin (RSE)

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 Acetaminophen
APAP

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

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493311

Locations

United States, Texas
Scirex Research Center
Austin, Texas, United States, 78705

Sponsors and Collaborators

Cadence Pharmaceuticals

Investigators

Study Director:

Mike Royal, MD, JD, MBA

Medical Monitor

More Information

No publications provided

Responsible Party:	Mike Royal, MD, JD, MBA- Vice President Clinical Development-Analgesics, Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00493311 History of Changes
Other Study ID Numbers:	CPI-APF-302
Study First Received:	June 27, 2007
Results First Received:	September 25, 2009
Last Updated:	November 29, 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