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

NCT05485805 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 220932022-003274-22
• Study Type: interventional
• Target: 541
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Dental Pain

Keywords

Dental pain

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 8 hours post-dose

Secondary Outcomes (15)

• 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

Study Arms (5)

Naproxen sodium/caffeine - Dose 1

EXPERIMENTAL

Participants will receive a single dose of one tablet of naproxen sodium/caffeine plus one tablet of placebo after extraction of third molars.

Drug: Naproxen sodium and caffeine (BAY2880376)

Naproxen sodium/caffeine - Dose 2

EXPERIMENTAL

Participants will receive a single dose of two tablets of naproxen sodium/caffeine after extraction of third molars.

Drug: Naproxen sodium and caffeine (BAY2880376)

Naproxen sodium

EXPERIMENTAL

Participants will receive a single dose of one tablet of naproxen sodium plus one tablet of placebo after extraction of third molars.

Drug: Naproxen sodium (Aleve)

Caffeine

EXPERIMENTAL

Participants will receive a single dose of two tablets of caffeine after extraction of third molars.

Drug: Caffeine

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of two tablets of matching placebo after extraction of third molars.

Drug: Placebo

Interventions

Naproxen sodium and caffeine (BAY2880376) DRUG

Tablet, oral use, single dose

Naproxen sodium/caffeine - Dose 1; Naproxen sodium/caffeine - Dose 2

Naproxen sodium (Aleve) DRUG

Tablet, oral use, single dose

Naproxen sodium

Caffeine DRUG

Tablet, oral use, single dose

Caffeine

Placebo DRUG

Tablet, oral use, single dose

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

JBR Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

MeSH Terms

Conditions

Toothache

Interventions

Naproxen; Caffeine

Condition Hierarchy (Ancestors)

Tooth Diseases; Stomatognathic Diseases; Facial Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Bayer Clinical Trials Contact
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 3, 2022
• Study Start: September 21, 2022
• Primary Completion: January 25, 2024
• Study Completion: January 29, 2024
• Last Updated: March 25, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)