A Study of Ibuprofen 250 mg / Acetaminophen 500 mg Comparing The Antipyretic (Fever Reduction) Effects in Healthy Male Volunteers

• Drug: Ibuprofen 250 mg / Acetaminophen 500 mg
  Ibuprofen 250 mg / Acetaminophen 500 mg
  Other Name: IBU 250 / APAP 500
• Drug: Ibuprofen 250 mg
  Ibuprofen 250 mg
  Other Name: IBU 250
• Drug: Acetaminophen 500 mg
  1 APAP 500 mg caplet
  Other Name: APAP 500
• Drug: Placebo
  Placebo tablet

• Experimental: Ibuprofen 250 mg / Acetaminophen 500 mg
  Single dose of 2 caplets of Ibuprofen 125 mg / Acetaminophen 250 mg by mouth
  Intervention: Drug: Ibuprofen 250 mg / Acetaminophen 500 mg
• Active Comparator: Ibuprofen 250 mg
  Single dose of 2 caplets of IBU 125 mg by mouth
  Intervention: Drug: Ibuprofen 250 mg
• Active Comparator: Acetaminophen 500 mg
  Single dose of 1 APAP 500 mg caplet + 1 placebo caplet by mouth
  Intervention: Drug: Acetaminophen 500 mg
• Placebo Comparator: Placebo
  Single dose of 2 caplets of Placebo by mouth
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Healthy male subjects who, at the time of screening, are between 18 and 55 years of age, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
2. The subject must have a normal, stable body temperature at Screening and on Day 0. If the subject's oral temperature is not between 97.4°F and 98.8°F, then 2 additional oral temperature readings will be obtained within a 30 minute period. These 3 consecutive temperature readings must be between 97.4°F and 98.8°F, with the highest value within 0.4°F of the lowest temperature value.
3. Body Mass Index (BMI) of 17.5 to 37.0 kg/m2; and a total body weight 50 kg (110 lbs) at Screening.
4. The subject has demonstrably adequate veins, by visual inspection, for IV catheter insertion.

Exclusion Criteria:

1. Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (excluding untreated, asymptomatic, seasonal allergies at the time of dosing) within the last 5 years that may increase the risk associated with study participation.
2. Subjects with any gastrointestinal disorders (eg, gastrectomy, tracheostomy, esophageal surgeries, short gut syndrome, peptic ulcer disease, known or suspected obstructive disease, previous gastrointestinal surgery, felinization of the esophagus, hypomotility of the gastrointestinal track) that could affect the absorption, metabolism, or excretion of the study medication or affect the results of the ingestible thermometer.
3. Subjects at risk for excessive bleeding.
4. Subjects with a history of nasal polyps, angioedema, or significant or actively treated bronchospastic disease.
5. Screening supine blood pressure ?90 or ?140 mm Hg (systolic) or ?50 or ?90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is ?90 or ?140 mm Hg (systolic) or ?50 or ?90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three consecutive BP values should be used to determine the subject's eligibility.
6. Screening supine 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at Screening and on Day 1 prior to RSE administration. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three consecutive QTc or QRS values should be used to determine the subject's eligibility.
7. The subject has a history of recurrent or acute or chronic infections of any type or any findings suggestive of occult infection, such as tuberculosis, sinusitis, urinary tract infection, respiratory tract or dental (abscess) infection, etc., or those with a positive QuantiFERON Tuberculosis, Hepatitis B surface antigen, Hepatitis C antibody, and/or Human immunodeficiency virus (HIV) test at Screening. Also excluded are subjects with frequent (more than 3 outbreaks per year), recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study.
8. Subjects who have experienced cold/flu symptoms (ie, runny nose, cough, and/or fever) within 2 weeks prior to the first administration of study treatments.
9. Subjects with a reduction in heart rate to ?50 beats per minute or deemed to be at high risk of syncope and/or hypotension per the clinical judgment of the investigator following a carotid sinus massage procedure.