Study to Find Out the Optimal Dose of Caffeine in the Combination Tablet of Naproxen Sodium and Caffeine in Patients Experiencing Moderate to Severe Pain After Having Wisdom Teeth Removed
Condition: Pain, Postoperative
MeSH terms: Pain, Postoperative
Intervention: Naproxen sodium/Caffeine (BAY2880376); Naproxen sodium (Aleve); Caffeine; Placebo
Intervention description: Tablet, oral, single dose; Tablet, oral, single dose; Tablet, oral, single dose; Tablet, oral, single dose
Intervention MeSH terms: Naproxen; Caffeine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 193.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Dental pain

Summary:

      The researchers in this study wanted to find out the optimal dose of Caffeine in the
      combination tablet of Naproxen Sodium and Caffeine that works in patients experiencing
      moderate to severe pain after having wisdom teeth removed. In the US, Naproxen has been
      marketed since 1976, and Naproxen Sodium has been approved for over-the-counter (OTC) use
      since 1994 for the temporary relief of minor aches and pains. Caffeine, which is generally
      consumed as coffee, tea or cocoa, has been shown to enhance the effectiveness of various pain
      relievers, and therefore is accepted as an additive to painkillers like aspirin and
      acetaminophen. Patients participating in this study underwent a surgery to remove 3 or 4
      wisdom teeth. If the pain severity after the surgery met the study requirement, patients
      would receive oral tablet(s) of Naproxen Sodium and Caffeine, or Naproxen Sodium, or
      Caffeine, or placebo (drug with no active ingredient). Patients could also receive additional
      pain medication when needed. Researchers would also learn if the patients have any medical
      problems during the study.
    

Eligibility criteria:

        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.