Study to Find Out the Optimal Dose of Caffeine in the Combination Tablet of Naproxen Sodium and Caffeine in Patients Experiencing Moderate to Severe Pain After Having Wisdom Teeth Removed

NCT04132336 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 210692019-003513-33
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 1

Brief Summary

The researchers in this study wanted to find out the optimal dose of Caffeine in the combination tablet of Naproxen Sodium and Caffeine that works in patients experiencing moderate to severe pain after having wisdom teeth removed. 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 effectiveness of various pain relievers, and therefore is accepted as an additive to painkillers like aspirin and acetaminophen. Patients participating in this study underwent a surgery to remove 3 or 4 wisdom teeth. If the pain severity after the surgery met the study requirement, patients would receive oral tablet(s) of Naproxen Sodium and Caffeine, or Naproxen Sodium, or Caffeine, or placebo (drug with no active ingredient). Patients could also receive additional pain medication when needed. Researchers would also learn if the patients have any medical problems during the study.

Conditions

Pain, Postoperative

Keywords

Dental pain

Outcome Measures

Primary Outcomes (1)

• Sum of Pain Intensity Difference (SPID) Over 8 Hours

  Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was 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 these values over the specific time period. SPID over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction.

  Up to 8 hours post dose

Secondary Outcomes (12)

• Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose

  Up to 2 hours, 4 hours and 12 hours post dose

• Total Pain Relief (TOTPAR) Over 8 Hours

  Up to 8 hours post dose

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

  Up to 2 hours, 4 hours and 12 hours post dose

• Time to First Use of Rescue Medication

  Up to 12 hours post dose

• The Cumulative Percentage of Participants Taking Rescue Medication

  Up to 12 hours post dose

Study Arms (7)

Naproxen sodium/caffeine - Dose 1

EXPERIMENTAL

Participants received a single dose of two tablets of naproxen sodium/caffeine (low dose/medium low dose) after extraction of third molars

Drug: Naproxen sodium/Caffeine (BAY2880376)

Naproxen sodium/caffeine - Dose 2

EXPERIMENTAL

Participants received a single dose of two tablets of naproxen sodium/caffeine (low dose/low dose) after extraction of third molars

Drug: Naproxen sodium/Caffeine (BAY2880376)

Naproxen sodium/caffeine - Dose 3

EXPERIMENTAL

Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ medium low dose) plus one tablet of placebo after extraction of third molars

Drug: Naproxen sodium/Caffeine (BAY2880376)

Naproxen sodium/caffeine - Dose 4

EXPERIMENTAL

Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ low dose) plus one tablet of placebo after extraction of third molars

Drug: Naproxen sodium/Caffeine (BAY2880376)

Naproxen sodium

ACTIVE COMPARATOR

Participants received a single dose of one tablet of naproxen sodium (low dose) plus one tablet of placebo after extraction of third molars

Drug: Naproxen sodium (Aleve)

Caffeine

ACTIVE COMPARATOR

Participants received a single dose of two tablets of caffeine (medium low dose) after extraction of third molars

Drug: Caffeine

Placebo

PLACEBO COMPARATOR

Participants received a single dose of two tablets of matching placebo after extraction of third molars

Drug: Placebo

Interventions

Naproxen sodium/Caffeine (BAY2880376) DRUG

Tablet, oral, single dose

Naproxen sodium/caffeine - Dose 1; Naproxen sodium/caffeine - Dose 2; Naproxen sodium/caffeine - Dose 3; Naproxen sodium/caffeine - Dose 4

Naproxen sodium (Aleve) DRUG

Tablet, oral, single dose

Naproxen sodium

Caffeine DRUG

Tablet, oral, single dose

Caffeine

Placebo DRUG

Tablet, oral, single dose

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• 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 about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Pain, Postoperative; Toothache

Interventions

Naproxen; Caffeine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Tooth Diseases; Stomatognathic Diseases; Facial Pain

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

Limitations and Caveats

Other pre-specified outcomes (non-key secondary) "Time to first perceptible relief/meaningful relief/perceptible relief confirmed by meaningful relief" and "Cumulative percentage of subjects with at least '2-point PID' over time" were also analyzed

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: October 8, 2019
• First Posted: October 18, 2019
• Study Start: November 12, 2019
• Primary Completion: March 2, 2020
• Study Completion: March 3, 2020
• Last Updated: September 1, 2021
• Results First Posted: June 16, 2021

Record last verified: 2021-08

Locations

US (1)