Intervention: Naproxen Sodium
Trial phase: Phase 3
SMILES: COc1ccc2cc(C(C)C(=O)[O-])ccc2c1.[Na+]
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 203
Group description: Participants received two Naproxen sodium 220 mg tablets orally, single dose
Eligibility criteria:
Inclusion Criteria:

Healthy, ambulatory, male and female volunteers ages 12 and older

Scheduled to undergo surgical removal of a minimum of two third molars of which at least one has to be a mandibular third molar. The mandibular extraction(s) required by each subject must meet one of the following scenarios:

one full bony impaction
two partial bony impactions
one full bony impaction and one partial bony impaction
one full bony impaction and one soft tissue impaction
one full bony impaction and one erupted third molar. Two full bony mandibular impactions are not allowed. Maxillary third molars may be removed regardless of impaction level.
Have moderate to severe postoperative pain on the Categorical Pain Rating Scale and a score of ≥ 50 mm on the 100-mm visual analog Pain Severity Rating Scale between 1600 hour and 1830 hour on the day of surgery
Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, Depo-Provera, or double-barrier and have a negative pregnancy test at Screening and prior to surgery. Female subjects of nonchildbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy
Provide a personally signed and dated informed consent indicating that the subject has been informed of all pertinent aspects of the trial, (subjects <18 years of age must sign a written assent and have parental or guardian consent).

Exclusion Criteria:

History of hypersensitivity to naproxen, diphenhydramine, nonsteroidal anti-inflammatory drug (NSAIDS), tramadol, aspirin or any other antihistamine and similar pharmacological agents or components of the products
Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years
Relevant concomitant disease such as asthma (exercise induced asthma is permitted), chronic sinusitis or nasal structural abnormalities causing greater than 50 percent obstruction (polyposis nasi, marked septal deviation) that can interfere with the conduct of the study in the judgment of the investigator
Current or past history of bleeding disorder(s)
Acute illness or local infection prior to surgery that can interfere with the conduct of the study in the judgment of the investigator
Chronic use of antihistamines defined as using 5 or more times a week for 2 or more consecutive weeks during the past 3 months
Positive alcohol breathalyzer test and positive urine drug test prior to surgery
Females who are pregnant or lactating
Chronic or severe sleep problems that do not respond to / Over the Counter (OTC) medication and requires a prescription hypnotic or sedative
Habitually spends less than 6.5 hours in bed