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

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, atRandomization

• 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 tocommunicate meaningfully with the Study Investigator and staff

• Be free of physical, mental, or medical conditions which, in the opinion of theInvestigator, may confound quantifying assessments for the Study

• Be willing to abstain from smoking cigarettes or using nicotine products from the timeof admission to Clinic until Study Completion Inclusion Criteria (Pre-Randomization) To be eligible for entry into the Study, Subjectsmust meet each of the following criteria prior to Randomization:

• Be free of evidence of infection based upon clinical assessment and blood (CompleteBlood 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 threeassessments performed during a 30 minute period

• Not develop a medically significant allergic or exaggerated systemic response toadministration of a test dose of reference standard endotoxin

• Develop a core temperature of at least 38.6 ºC (101.5 ºF) after intravenous referencestandard endotoxin dosed per Study guidelines and have a fever response to endotoxinthat is at or near the peak temperature by virtue of two consecutive temperatureassessments 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 daysof clinic admission (aspirin at low dose for cardiac prophylaxis is allowed, butshould not be taken on the day of the Study)

• Has significant medical disease(s), laboratory abnormalities, or condition(s) that inthe Investigator's judgment could compromise the Subject's welfare, ability tocommunicate with the Study staff, complete Study activities, or would otherwisecontraindicate Study participation.

• Has known hypersensitivity or contraindication to receiving endotoxin that in theInvestigator's clinical judgment merits discontinuation from further Studyparticipation

• Has known hypersensitivity to acetaminophen, the inactive ingredients (excipients) ofthe 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 asdefined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)criteria

• Has a history of nasal polyps, angioedema, significant or actively treatedbronchospastic disease, or any other significant medical condition thatcontraindicates participation in the Study or receiving endotoxin, Study Medication,or Rescue Medication

• Has an active infection or other disease or condition that may cause abnormalalterations in body temperature, or has worked the night shift on a regular basis forthe last 3 months prior to Screening

• Has impaired liver function, e.g. Alanine aminotransferases (ALT) greater than orequal to 3 times the upper limit of normal, bilirubin greater than 3.0, active hepaticdisease, or evidence of clinically significant liver disease (e.g., cirrhosis orhepatitis)

• Has participated in another clinical Study (investigational or marketed product)within 30 days of Screening