Study of the Efficacy and Safety of Intravenous vs Oral Acetaminophen for Treatment of Fever in Healthy Adult Males
Condition: Fever
MeSH terms: Fever
Intervention: Intravenous acetaminophen plus oral placebo; Oral acetaminophen plus IV placebo; Reference standard endotoxin (RSE)
Intervention description: Single dose of 1 gm IV acetaminophen; Single dose of 1 g PO APAP; 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.
Intervention MeSH terms: Acetaminophen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 105.0
Sex: Male
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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
    

Eligibility 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