A Study to Learn How Well a Single Dose of the Study Treatment Naproxen Sodium and Caffeine Combined in One Tablet (Fixed-dose Combination) Works to Relieve Pain After Dental Surgeries Compared to the Single Ingredients and to Placebo

Bayer541 enrolled

Overview

Researchers are looking for a better way to relieve pain in people, such as after dental surgery. Participants in this study, have had 3 or 4 third molars (cheek teeth) removed and subsequently have moderate to severe tooth pain. The study treatment naproxen sodium suppresses inflammatory pain by reducing inflammation. 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 effect of various painkillers, and therefore is accepted as an additive. The main purpose of this study is to learn how well a fixed-dose combination of naproxen sodium and caffeine relieves pain compared to each single ingredient as well as to placebo in participants after molar removal. A placebo is a treatment that looks like a medicine but does not have any medicine in it. To answer this, the researchers will compare the amount of pain decrease over 8 hours in participants who received a single dose of either: * 1 fixed-dose tablet of naproxen sodium/caffeine * 2 fixed-dose tablets of naproxen sodium/caffeine * naproxen sodium only * caffeine only * or placebo The study participants will be randomly (by chance) assigned to one of the five treatment groups. They will take a single dose of two tablets by mouth within 4.5 hours after the surgery. If there is no pain relief within 2 hours after intake, other painkillers may be given.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

541

Conditions

Postoperative Dental Pain

Eligibility

Sex: ALLMin age: 16 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose

Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be calculated by multiplying the PID score at each post dose time point by the duration (in hours) since the preceding time point and then summing the values over the relevant time period. For SPID (0-8), eight PIDs are summed up, which is minimally 0, if there is no pain relief or maximally 80, if there is very strong pain and significant pain relief.

Time frame: Up to 8 hours post-dose

Secondary Outcomes

Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose

Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be calculated by multiplying the PID score at each post dose time point by the duration (in hours) since the preceding time point and then summing the values over the relevant time period. For SPID(0-i), i PIDs are summed up, which minimally is 0, if there is no pain relief or maximally i\*10, if there is very strong pain and significant pain relief.

Time frame: from 0 to 2, 4, 6, 12 and 24 hours post-dose

Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose

Total Pain Relief (TOTPAR) is a cumulative measure that evaluates the overall pain relief over a specific time frame from 0-2,0-4,0-6,0-8,0-12 and 0-24 following drug administration. It is calculated by multiplying the pain relief score from the categorical pain relief scale at each time post-dose time by multiplying the duration (in hours) since the preceding time point and then adding these values. Categorical Pain Relief Scale measure the degree of pain relief using a scale from 0 to 4, in which 0 is no relief, 1 a little relief, 2 some relief, 3 a lot of relief and 4 complete relief. Higher values of TOTPAR indicates better pain relief and suggest that the investigational product provided consistence and meaningful pain relief over the period. Low TOTPAR values indicates minimal pain relief or short-lasting efficacy.

Time frame: up to 24 hours post-dose

Time to First Use of Rescue Medication