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

Condition(s) targeted: Fever

Intervention: IV APAP (acetominophen) or IV Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Cadence Pharmaceuticals

Official(s) and/or principal investigator(s):
Mike Royal, MD, JD, MBA, Study Director, Affiliation: Medical Monitor

Overall contact:
Mike Royal, MD, JD, MBA, Phone: 858-436-1427, Email: mroyal@cadencepharm.com

A research study to determine if acetaminophen 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.

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

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Detailed description: 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

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Male.

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 (CBC) and urine testing

- Have an average baseline oral temperature that is equal to or below 37ºC (98. 6ºF) and does not vary more than 0. 4ºC (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. 6ºC (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. 4ºF) of each other

Exclusion Criteria:

- Has been treated with any medication having antipyretic effects (e. g., corticosteroid, 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 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 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., 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

Mike Royal, MD, JD, MBA, Phone: 858-436-1427, Email: mroyal@cadencepharm.com

Scirex Research Center, Austin, Texas 78705, United States; Recruiting
Stephen E Daniels, DO, Principal Investigator

Starting date: June 2007
Last updated: June 28, 2007