A Trial to Compare the Duration of Analgesic Efficacy and Safety of Naproxen Sodium Tablets and Ibuprofen Tablets in Postsurgical Dental Pain

A Randomized, Double-Blind, Placebo-Controlled Trial to Compare the Duration of Analgesic Efficacy and Safety of Naproxen Sodium Tablets and Ibuprofen Tablets in Postsurgical Dental Pain

To compare the duration of analgesic efficacy as determined by the time to rescue medication of a single oral dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo over 24 hours in subjects experiencing moderate to severe post-impaction surgery dental pain.

To compare the overall analgesic effect (SPID 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo.

To compare the overall relief from pain (TOTPAR 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Naproxen Sodium (Aleve, BAY117031); Drug: Ibuprofen (Advil); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 387
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, ambulatory, male or female volunteers 16-40 years of age;
• Body mass index 18.0 to 30.0 kg/m^2 inclusive;
• Scheduled to undergo surgical removal of at least 2 mandibular partial or full bony impacted third molars. Up to two maxillary third molars may be removed regardless of impaction level. Supernumerary teeth present may also be removed at the discretion of the oral surgeon;
• Mandibular molars must demonstrate modified Demirjian root classification stage D, E, F, G or H;

Exclusion Criteria:

• History of hypersensitivity to naproxen sodium, ibuprofen, nonsteroidal anti-inflammatory drugs (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, hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;
• Relevant concomitant disease such as asthma (exercise induced asthma is permitted)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naproxen Sodium (Aleve, BAY117031); Participants received one single dose of 440 mg naproxen sodium tablets (200 mg x 2 tablets, oral) after randomization	Drug: Naproxen Sodium (Aleve, BAY117031); 220 mg x 2 tablets, oral, single dose
Active Comparator: Ibuprofen (Advil); Participants received one single dose of 400 mg ibuprofen tablets (200 mg x 2 tablets, oral) after randomization	Drug: Ibuprofen (Advil); 200 mg x 2 tablets, oral, single dose
Placebo Comparator: Placebo; Participants received one single dose of matching placebo tablets (2 tablets, oral) after randomization	Drug: Placebo; Matching placebo, 2 tablets, oral, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Use of Rescue Medication	Time to first use of rescue medication was estimated using Kaplan-Meier method. If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.	Up to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Difference (SPID)	Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted sum of pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.	Up to 24 hours
Total Pain Relief (TOTPAR)	Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.	Up to 24 hours

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Cooper SA, Desjardins P, Brain P, Paredes-Diaz A, Troullos E, Centofanti R, An B. Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial. Curr Med Res Opin. 2019 Dec;35(12):2149-2158. doi: 10.1080/03007995.2019.1655257. Epub 2019 Aug 27.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): July 6, 2018
• Study Completion (Actual): July 10, 2018

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Postsurgical pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Ibuprofen; Naproxen
• Other Study ID Numbers: 19762; 2017-005049-67 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes