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

This study has been completed.
Sponsor:
Information provided by:
Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00493311
First received: June 27, 2007
Last updated: November 29, 2010
Last verified: November 2010
  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 3

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:


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

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 April 17, 2014