A Randomized, Double-Blind, Single-Dose, Parallel, Placebo-Controlled Pivotal Trial to Confirm the Efficacy of a Fixed Dose Combination Tablet of Naproxen Sodium and Caffeine to Effectively Alleviate Postsurgical Dental Pain
Overview
- Phase
- Phase 3
- Intervention
- Naproxen sodium and caffeine (BAY2880376)
- Conditions
- Postoperative Dental Pain
- Sponsor
- Bayer
- Enrollment
- 541
- Locations
- 1
- Primary Endpoint
- Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
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;
Arms & Interventions
Naproxen sodium/caffeine - Dose 1
Participants will receive a single dose of one tablet of naproxen sodium/caffeine plus one tablet of placebo after extraction of third molars.
Intervention: Naproxen sodium and caffeine (BAY2880376)
Naproxen sodium/caffeine - Dose 2
Participants will receive a single dose of two tablets of naproxen sodium/caffeine after extraction of third molars.
Intervention: Naproxen sodium and caffeine (BAY2880376)
Naproxen sodium
Participants will receive a single dose of one tablet of naproxen sodium plus one tablet of placebo after extraction of third molars.
Intervention: Naproxen sodium (Aleve)
Caffeine
Participants will receive a single dose of two tablets of caffeine after extraction of third molars.
Intervention: Caffeine
Placebo
Participants will receive a single dose of two tablets of matching placebo after extraction of third molars.
Intervention: Placebo
Outcomes
Primary Outcomes
Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose
Time Frame: Up to 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.
Secondary Outcomes
- Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose(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(up to 24 hours post-dose)
- Time to First Use of Rescue Medication(Up to 24 hours post-dose)
- The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period(Up to 24 hours post-dose)
- Time to First Perceptible Relief Measured by a Stopwatch(Up to 24 hours post-dose)
- Time to Meaningful Relief Measured by a Stopwatch(Up to 24 hours post-dose)
- Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief(Up to 24 hours post-dose)
- Pain Intensity Difference (PID)(up to 24 hours post-dose)
- Pain Relief Score(Up to 24 hours post-dose)
- Peak Pain Intensity Difference (PID)(Up to 24 hours post-dose)
- Number of Participants With Certain Peak Pain Relief Score(Up to 24 hours post-dose)
- Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time(Up to 24 hours post-dose)
- Global Assessment of Pain Relief of the Investigational Product(24 hours post-dose)
- Number of Participants With Adverse Events(Up to 5 days post-dose)
- Number of Participants With Significant Changes in Vital Signs Since Baseline(Up to 5 days post-dose)