A Study to Learn How Well a Single Dose of the Study Treatment Naproxen Sodium and Caffeine Combined in One Tablet (Fixed-dose Combination) Works to Relieve Pain After Dental Surgeries Compared to the Single Ingredients and to Placebo

This is an interventional treatment trial for Postoperative Dental Pain focused on measuring Dental pain Read More

Inclusion Criteria:

• Healthy, ambulatory, male or female volunteers 16 years of age or older;
• Body mass index (BMI) 18.5 to 35.0 kg/m^2 inclusive as measured by the National Institutes of Health (NIH) BMI Calculator;
• Participants will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios: two full bony impactions; two partial bony impactions; one full bony impaction in combination with one partial bony impaction. Supernumerary teeth present may also be removed at the discretion of the oral surgeon;
• Have not taken any form of medication, nutritional supplements with analgesic properties (e.g. gamma-Aminobutyric acid [GABA], turmeric) or herbal supplements (i.e., St. John's Wort) within 5 days of admission (except for oral contraceptives, prophylactic antibiotics, multivitamin supplements, or other routine medications to treat benign conditions (such as antibiotics to treat acne), and agree not to take any medication (other than that provided to them) throughout the study;
• Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator;
• Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity Numerical Rating Scale (NRS) within 4.5 hours post-surgery.

Exclusion Criteria:

• History of hypersensitivity to naproxen sodium, caffeine, ibuprofen, nonsteroidal anti-inflammatory drug (NSAIDS), aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational products;
• Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension and cardiac arrhythmia), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;
• Participants with the following medical conditions may be eligible at the discretion of the investigator: attention deficit hyperactivity disorder (ADHD) on a stable dose regimen of methylphenidate/(dextro) amphetamine for at least 6 months; participants with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months;
• Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months;
• Relevant concomitant disease such as asthma (exercise induced asthma is permitted);
• Current or past history of gastrointestinal ulceration, gastrointestinal bleeding or other bleeding disorder(s);
• Acute illness or active local infection prior to surgery that can interfere with the conduct of the study in the judgment of the investigator;
• Use of any over-the-counter (OTC) or prescription medications with which the administration of naproxen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated;
• Use of any medications within 5 days of surgery until discharge from the study site (except oral contraceptives, prophylactic antibiotics, synthetic thyroid hormones, methylphenidate or medications to treat benign conditions such as antibiotics to treat acne);
• Use of caffeine within 2 days prior to the study;
• Habits of high consumption of caffeine (>400 mg/day equivalent to about 3-4 cups of coffee per day);
• Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years);
• Surgeon's trauma rating of severe following surgery.