• Analgesic efficacy for the 8-12 hour dosing interval after Dose 1 using SPID. [ Time Frame: 8 - 12 hours ] [ Designated as safety issue: No ]
• Durability of effect as measured by the proportion of subjects in the Ibuprofen ER group achieving meaningful improvement in PID from baseline at all three assessment periods of 24, 36, and 48 hours. [ Time Frame: 24, 36, and 48 hours ] [ Designated as safety issue: No ]

• Time to confirmed "first perceptible" relief. [ Time Frame: Within 4 hours post Dose 1 ] [ Designated as safety issue: No ]
• Time to confirmed "meaningful" relief. [ Time Frame: Within 12 hours post Dose 1 ] [ Designated as safety issue: No ]
• Proportion of subjects in the Ibuprofen ER group with "first perceptible" relief within 1 hour of Dose 1. [ Time Frame: Within 1 hour of Dose 1 ] [ Designated as safety issue: No ]
• Proportion of subjects in the Ibuprofen ER group achieving "meaningful" relief. [ Time Frame: Within 12 hours post Dose 1 ] [ Designated as safety issue: No ]
• Analgesic efficacy for the 0-12, 0-4, 4-8, and 4-12 hour dosing intervals after Dose 1 using TOTPAR and SPID. [ Time Frame: 0-12 hours after Dose 1 ] [ Designated as safety issue: No ]
• Duration of relief after Dose 1. [ Time Frame: Time to rescue or at time of Dose 2 ] [ Designated as safety issue: No ]
• Proportion of subjects who are rescued at or prior to hour 8, hour 10, and hour 12 after taking Dose 1 [ Time Frame: 0-12 hours after taking Dose 1 ] [ Designated as safety issue: No ]
• Pain relief and PID scores at individual time points for Dose 1. [ Time Frame: 0-12 hours after taking Dose 1 ] [ Designated as safety issue: No ]
• Global evaluation for Dose 1. [ Time Frame: At 12 hours after Dose 1 or at time of rescue ] [ Designated as safety issue: No ]
• Global evaluation, maximum relief, and overall relief for Dose 2. [ Time Frame: At 24 hours or at time of rescue between 12 and 24 hours ] [ Designated as safety issue: No ]
• Global evaluation. maximum relief, and overall relief for Dose 3. [ Time Frame: At 36 hours or at time rescue between 24 and 36 hours ] [ Designated as safety issue: No ]
• Global evaluation, maximum relief, and overall relief for Dose 4. [ Time Frame: At 48 hours or at time of rescue between 36 and 48 hours. ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the efficacy and safety of multiple doses of Ibuprofen 600 mg Extended-Release Tablets in a study of dental pain following extraction of third molar teeth.

This is a single-center, multiple-dose, randomized, placebo-controlled, double-blinded, parallel group trial to evaluate the efficacy and safety of multiple doses of Ibuprofen 600 mg Extended-Release Tablets in a study of dental pain following extraction of third molar teeth. The surgery will consist of surgical extraction of 1-2 impacted third molars, of which one must be a mandibular impaction that is partially impacted in either tissue or bone. Subjects will be stratified according to baseline pain intensity numerical rating and gender.

• Pain
• Post-Operative Pain
• Third Molar Extraction

• Drug: Ibuprofen 600 mg Extended-Release Tablets
• Drug: Placebo

• Experimental: One-hundred and sixty subjects will be randomly assigned to the Ibuprofen 600 mg ER treatment group based on gender and baseline pain intensity rating.
• Placebo Comparator: Eighty subjects will be randomly assigned to the Placebo treatment group based on gender and baseline pain intensity rating.

Inclusion Criteria:

• Males and females 16 to 45 years of age;
• Outpatients scheduled to undergo surgical extraction of 1-2 impacted third molar(s), one of which must be a mandibular impaction that is partially impacted in either tissue or bone;
• At least a score of 5 on the 11-point pain intensity numerical rating scale (PI-NRS) at baseline;
• Use of only the following preoperative medication(s) / anesthetic(s): short-acting local anesthetic (e.g., mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide;
• Reliable, cooperative, and adequate intelligence to record the requested information on the analgesic questionnaire form;
• Subjects (or the parent or legal guardian of subjects under the age of 18 years) are required to read, comprehend, and sign the informed consent. Subjects requiring a parent or legal guardian to sign the informed consent will be required to sign an assent;
• Examined by the attending dentist or physician and medically cleared to participate in the study; and,
• In general good health and have no contraindications to any of the study meds.

Exclusion Criteria:

• Presence of a serious medical condition (e.g., poorly controlled hypertension, poorly controlled diabetes, significantly impaired cardiac, renal or hepatic function, hyper- or hypothyroidism);
• Use of a prescription or nonprescription drug with which the administration of ibuprofen, celecoxib, any other NSAID, or acetaminophen, is contraindicated;
• Acute local infection at the time of surgery that could confound the post-surgical evaluation;
• Females who are pregnant, lactating, of child-bearing potential, or postmenopausal for less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a urine-based pregnancy test;
• Presence or history (within 2 years of enrollment) of bleeding disorder(s) or peptic ulcer disease;
• Presence or history (within the past year) of alcoholism or substance abuse. Subjects who are taking CNS or other psychotropic drugs (including St. John's Wort, or any other nutritional supplement known to have psychotropic effects) may be enrolled if they have been on stable doses of medication for at least 2 months, will maintain this dose throughout the study, and their condition is judged by the Principal Investigator to be well-controlled;
• Habituation to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week);
• History of allergic reaction (eg, asthma, rhinitis, swelling, shock, or hives) to ibuprofen, naproxen, aspirin, celecoxib, any other NSAID, or acetaminophen;
• Prior use of any type of analgesic or NSAID 5 half-lives of that drug or less before taking the first dose of study medication, except for pre-anesthetic medication and anesthesia for the procedure;
• Ingestion of any caffeine-containing beverages, chocolate, or alcohol 4 hours or less before taking the first dose of study medication;
• Has taken an investigational product within the past 30 days;
• Has previously been entered into this study; and,
• The subject is a member of the study site staff either directly involved with the study, an employee of the Sponsor, or a relative of study site personnel directly involved with the study or Sponsor.

• AAIPharma
• Jean Brown Research