Clinical trial NCT04132336: 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
Official title: A Randomized, Double-Blind, Single-Dose, Parallel, Placebo-Controlled Trial to Determine the Dose of Caffeine in a Fixed Dose Combination Tablet of Naproxen Sodium and Caffeine to Effectively Alleviate Postsurgical Dental Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain, Postoperative
Keywords: Dental pain
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2019-10-18
Enrollment: 193
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Sum of Pain Intensity Difference (SPID) Over 8 Hours
timeFrame: Up to 8 hours post dose
Secondary outcomes:
measure: Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose
timeFrame: Up to 2 hours, 4 hours and 12 hours post dose
measure: Total Pain Relief (TOTPAR) Over 8 Hours
timeFrame: Up to 8 hours post dose
measure: Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose
timeFrame: Up to 2 hours, 4 hours and 12 hours post dose
measure: Time to First Use of Rescue Medication
timeFrame: Up to 12 hours post dose
measure: The Cumulative Percentage of Participants Taking Rescue Medication
timeFrame: Up to 12 hours post dose
measure: Pain Intensity Difference (PID) at Each Evaluation
timeFrame: Up to 12 hours post dose
measure: Peak Pain Intensity Difference (PID)
timeFrame: Up to 12 hours post dose
measure: Pain Relief Score at Each Evaluation
timeFrame: Up to 12 hours post dose
measure: Peak Pain Relief Score
timeFrame: Up to 12 hours post dose
measure: Global Assessment of the Investigational Product
timeFrame: Up to 12 hours post dose
measure: Number of Participants With Adverse Events
timeFrame: Up to 5 days post dose
measure: The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs
timeFrame: Up to 5 days post dose
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: JBR Clinical Research
state: Utah
Study officials:
References: