Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain
Condition: Pain, Postoperative; Tooth Diseases
MeSH terms: Tooth Diseases; Pain, Postoperative
Intervention: ibuprofen + caffeine; ibuprofen; ibuprofen; caffeine; ibuprofen + caffeine; placebo; placebo; caffeine; ibuprofen; ibuprofen + caffeine
Intervention description: FDC tablet; tablet.; tablet; tablet; Fixed Dose Combination (FDC) tablet; tablet; tablet; tablet; tablet; FDC tablet
Intervention MeSH terms: Ibuprofen; Caffeine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 562.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to compare the efficacy of a combination product
      containing ibuprofen 400 mg and caffeine 100 mg versus either ingredient alone as well as
      placebo for the treatment of post-surgical dental pain over an eight-hour period followed by
      a single dose of study medication (study stage 1). A secondary objective is to evaluate
      efficacy of multiple doses of the combination in comparison to ibuprofen alone over a 5-day
      post-surgical period (study stage 2).
    

Eligibility criteria:

        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 be
             partial bony impactions or full bony impactions (as long as the trauma rating is not
             severe 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 mandibular
             being a soft tissue impaction or partial bony impaction. Maxillary third molars (or
             supernumerary teeth) of any type can be extracted;

          -  Use of only the following preoperative medication(s)/ anesthetic(s): topical
             benzocaine, short-acting local anesthetic (mepivacaine or lidocaine) with or without
             vasoconstrictor and/or nitrous oxide;

          -  Reliable, cooperative, and of adequate intelligence to record the requested
             information on the analgesic questionnaire form;

          -  Examined by the attending oral surgeon or physician and medically cleared to
             participate 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 any
             of the study medications or anesthetic drugs;

          -  Subjects have at least a categorical pain score of moderate and a numerical rating
             scale (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, poorly
             controlled diabetes, significantly impaired cardiac, renal or hepatic function, hyper-
             or hypothyroidism);

          -  Use of a prescription or non-prescription drug with which the administration of
             ibuprofen or any other non steroidal anti inflammatory or caffeine 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 post-menopausal
             for less than 2 years and not using a medically approved method of contraception
             (i.e., oral, transdermal, intravaginal 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;

          -  History of alcoholism or substance abuse within the last year, or is currently abusing
             alcohol or other mood-altering drugs (e.g., cannabis). Subjects who are taking central
             nervous system or other psychotropic drugs (including St. Johns 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 or caffeine (i.e., routine use of oral analgesics 5 or
             more times per week or ingestion of 4 or more caffeine-containing drinks daily); use
             of "high energy" drinks more than once per week;

          -  Use of any type of systemic corticosteroid within the past 30 days or a history of
             current or previous use of anabolic steroids;

          -  History of allergic reaction (e.g., asthma, rhinitis, swelling, shock, or hives) to
             acetaminophen, ibuprofen, naproxen, aspirin, celecoxib, or any other non steroidal
             anti inflammatory or caffeine;

          -  Prior use of any type of analgesic or non steroidal anti inflammatory within 5
             half-lives of that drug before surgery, except for pre-anesthetic medication and
             anesthesia for the procedure;

          -  Ingestion of any caffeine-containing beverages, chocolate, or alcohol 6 hours or less
             before surgery;

          -  Has impaired liver function, e.g., serum Alanine transaminase, aspartate
             aminotransferase, alkaline phosphatase, or Gamma-glutamyltransferase greater than 2.5
             times the upper limit of normal, or blood urea nitrogen, creatinine, or bilirubin
             greater 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 as
             determined 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 the
             study, an employee of the Sponsor, or a relative of study site personnel directly
             involved with the study or Sponsor.