Clinical trial NCT05485805: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Dental Pain
Keywords: Dental pain
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2022-08-03
Enrollment: 541
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 Post-dose
timeFrame: Up to 8 hours post-dose
Secondary outcomes:
measure: Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose
timeFrame: from 0 to 2, 4, 6, 12 and 24 hours post-dose
measure: Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose
timeFrame: up to 24 hours post-dose
measure: Time to First Use of Rescue Medication
timeFrame: Up to 24 hours post-dose
measure: The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period
timeFrame: Up to 24 hours post-dose
measure: Time to First Perceptible Relief Measured by a Stopwatch
timeFrame: Up to 24 hours post-dose
measure: Time to Meaningful Relief Measured by a Stopwatch
timeFrame: Up to 24 hours post-dose
measure: Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief
timeFrame: Up to 24 hours post-dose
measure: Pain Intensity Difference (PID)
timeFrame: up to 24 hours post-dose
measure: Pain Relief Score
timeFrame: Up to 24 hours post-dose
measure: Peak Pain Intensity Difference (PID)
timeFrame: Up to 24 hours post-dose
measure: Number of Participants With Certain Peak Pain Relief Score
timeFrame: Up to 24 hours post-dose
measure: Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time
timeFrame: Up to 24 hours post-dose
measure: Global Assessment of Pain Relief of the Investigational Product
timeFrame: 24 hours post-dose
measure: Number of Participants With Adverse Events
timeFrame: Up to 5 days post-dose
measure: Number of Participants With Significant Changes in Vital Signs Since Baseline
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: