Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain

Inclusion criteria:

• Males and females 18 to 55 years of age;

• Outpatients scheduled to undergo surgical extraction of 3-4 impacted third molar(s),with a minimum of two mandibular extractions. The two mandibular third molars may bepartial bony impactions or full bony impactions (as long as the trauma rating is notsevere and the surgeons do not feel the subject will have extreme post-surgical pain)OR there may be a combination of one full bony impaction with the second mandibularbeing a soft tissue impaction or partial bony impaction. Maxillary third molars (orsupernumerary teeth) of any type can be extracted;

• Use of only the following preoperative medication(s)/ anesthetic(s): topicalbenzocaine, short-acting local anesthetic (mepivacaine or lidocaine) with or withoutvasoconstrictor and/or nitrous oxide;

• Reliable, cooperative, and of adequate intelligence to record the requestedinformation on the analgesic questionnaire form;

• Examined by the attending oral surgeon or physician and medically cleared toparticipate in the study;

• Scheduled to undergo a qualifying surgical procedure;

• In good general health, with a BMI of 30 or less, and have no contraindications to anyof the study medications or anesthetic drugs;

• Subjects have at least a categorical pain score of moderate and a numerical ratingscale (NRS) score of 5 or greater within 4.5 hours from the time of the last suture.

Exclusion criteria:

• Presence of a serious medical condition (e.g., poorly controlled hypertension, poorlycontrolled diabetes, significantly impaired cardiac, renal or hepatic function, hyper-or hypothyroidism);

• Use of a prescription or non-prescription drug with which the administration ofibuprofen or any other non steroidal anti inflammatory or caffeine is contraindicated;

• Acute local infection at the time of surgery that could confound the post-surgicalevaluation;

• Females who are pregnant, lactating, of child-bearing potential, or post-menopausalfor less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, intravaginal or implanted contraceptives, intrauterinedevice, diaphragm, condom, abstinence, or surgical sterility), or females who testpositive on a urine-based pregnancy test;

• Presence or history (within 2 years of enrollment) of bleeding disorder(s) or pepticulcer disease;

• History of alcoholism or substance abuse within the last year, or is currently abusingalcohol or other mood-altering drugs (e.g., cannabis). Subjects who are taking centralnervous system or other psychotropic drugs (including St. Johns Wort, or any othernutritional supplement known to have psychotropic effects) may be enrolled if theyhave been on stable doses of medication for at least 2 months, will maintain this dosethroughout the study, and their condition is judged by the Principal Investigator tobe well-controlled;

• Habituation to analgesic drugs or caffeine (i.e., routine use of oral analgesics 5 ormore times per week or ingestion of 4 or more caffeine-containing drinks daily); useof "high energy" drinks more than once per week;

• Use of any type of systemic corticosteroid within the past 30 days or a history ofcurrent or previous use of anabolic steroids;

• History of allergic reaction (e.g., asthma, rhinitis, swelling, shock, or hives) toacetaminophen, ibuprofen, naproxen, aspirin, celecoxib, or any other non steroidalanti inflammatory or caffeine;

• Prior use of any type of analgesic or non steroidal anti inflammatory within 5half-lives of that drug before surgery, except for pre-anesthetic medication andanesthesia for the procedure;

• Ingestion of any caffeine-containing beverages, chocolate, or alcohol 6 hours or lessbefore surgery;

• Has impaired liver function, e.g., serum Alanine transaminase, aspartateaminotransferase, alkaline phosphatase, or Gamma-glutamyltransferase greater than 2.5times the upper limit of normal, or blood urea nitrogen, creatinine, or bilirubingreater than 1.5 times the upper limit of normal without a known benign explanation;

• Has known history of a positive HIV antibody test or known HIV infection;

• Has a known history of Hepatitis B or C;

• Has a clinically significant abnormal electrocardiogram (ECG) at screening asdetermined by the Investigator:

• Has taken an investigational product within the past 30 days;

• Has previously been entered into this study;

• The subject is a member of the study site staff either directly involved with thestudy, an employee of the Sponsor, or a relative of study site personnel directlyinvolved with the study or Sponsor.