check_circleStudy Completed

Postoperative dental pain

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

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

16 - N/A
  • - 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.
  • - 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.

Trial summary

Enrollment Goal
541
Trial Dates
September 2022 - January 2024
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Naproxen sodium and caffeine (BAY2880376)
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
JBR Clinical ResearchSalt Lake City, 84107, United States

Primary Outcome

  • Sum of pain intensity difference (SPID) over 8 hours post-dose
    date_rangeTime Frame:
    Up to 8 hours post-dose

Secondary Outcome

  • Sum of pain intensity differences from 0 to 2, 4, 6, 12 and 24 hours post-dose
    date_rangeTime 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
    date_rangeTime Frame:
    up to 24 hours post-dose
  • Time to first use of rescue medication
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • The cumulative proportion of participants taking rescue medication over the 24 hour period
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Time to first perceptible relief measured by a stopwatch
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Time to meaningful relief measured by a stopwatch
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Time to first perceptible relief confirmed by meaningful relief defined as the time to perceptible pain relief
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Pain intensity difference (PID)
    date_rangeTime Frame:
    up to 24 hours post-dose
  • Pain relief score
    Pain Relief Score (PRS): 0 = No Relief; 1 = A Little Relief; 2 = Some Relief; 3 = A Lot of Relief; 4 = Complete Relief.
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Peak pain intensity difference (PID)
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Number of participants with certain peak pain relief score
    Number of participants with pain relief score 4, 3, 2, 1
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Cumulative percent of participants with ‘at least a 2-point PID’ over time
    date_rangeTime Frame:
    Up to 24 hours post-dose
  • Global assessment of pain relief of the investigational product
    Number of participants with overall rating poor, fair, good, very good, excellent 24 hour post-dose
    date_rangeTime Frame:
    24 hours post-dose
  • Number of participants with adverse events
    date_rangeTime Frame:
    Up to 5 days post-dose
  • Number of participants with significant changes in vital signs since baseline
    date_rangeTime Frame:
    Up to 5 days post-dose

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
5