Study to Collect Information on How Well the Study Drug Naproxen Sodium Tablets Works Compared to Hydrocodone/Acetaminophen Tablets in Order to Relieve Pain in Participants Experiencing Moderate to Severe Pain After Having Their Wisdom Teeth Removed

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

With this study researchers want to collect information on how long the pain relief lasts after a fixed dose of naproxen sodium or hydrocodone/acetaminophen or placebo (contains no medication) over 12 hours in subjects experiencing moderate to severe pain after having their wisdom teeth removed. Naproxen Sodium (Aleve®) is a drug that is used for the temporary relief of minor aches and pains.

Hydrocodone/Acetaminophen is a combination drug used to relieve moderate to severe pain. It contains an opioid (narcotic) pain reliever (hydrocodone) and a non-opioid pain reliever (acetaminophen).

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Naproxen Sodium (Aleve, BAY117031); Drug: Hydrocodone/Acetaminophen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, ambulatory, male or female volunteers 18 to 40 years of age;

• Subjects 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 consumed alcoholic beverages, or foods and beverages containing caffeine (examples; coffee, tea, chocolate, and colas) after midnight prior to surgery and agree not to consume any of these foods or beverages throughout their stay at the study site;
• 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 NRS within 4.5 hours postsurgery;
• Ability to understand and follow study-related instructions;
• Be willing and able to participate in all scheduled visits, treatment plan, and trial procedures according to the clinical protocol;

Exclusion Criteria:

• History of hypersensitivity to naproxen sodium, hydrocodone/acetaminophen, ibuprofen, 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), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;
• Subjects with the following medical conditions may be eligible at the discretion of the investigator: ADHD on a stable dose regimen of methylphenidate/(dextro)amphetamine for at least 6 months; subjects 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;
• Use of any OTC or prescription medications with which the administration of naproxen, hydrocodone/acetaminophen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated;
• Females who are planning to become pregnant, pregnant or lactating;
• 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);
• Alcoholism or drug abuse within 2 years prior to the Screening Visit or routine consumption of 3 or more alcohol containing beverages per day; Alcohol containing beverages are defined as one beer (5%), one glass of wine (11%) and one shot (40%) hard liquor;
• Surgeon's trauma rating of severe following surgery;
• Unwilling or unable to comply with all requirements outlined in the protocol;

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; After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Naproxen Sodium (Aleve, BAY117031); 220 mg per tablet, two tablets (440 mg), intake a single dose orally.
Active Comparator: Hydrocodone/Acetaminophen; After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Hydrocodone/Acetaminophen; 5/325 mg per tablet, two tablets (10/650 mg), intake a single dose orally.
Placebo Comparator: Placebo; After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Placebo; two tablets, intake a single dose orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Difference Over 12 Hours (SPID 0-12)	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 12 hours ranges from -120 to 120. A higher value indicates a better pain reduction.	Up to 12 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pain Relief Over 12 Hours (TOTPAR 0-12)	Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 12 hours ranges from 0 to 48, a higher value indicates more pain relief.	Up to 12 hours postdose
Total Pain Relief Over 6 Hours (TOTPAR 0-6)	Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 6 hours ranges from 0 to 24, a higher value indicates more pain relief.	Up to 6 hours postdose
Sum of Pain Intensity Difference Over 6 Hours (SPID 0-6)	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 6 hours ranges from -60 to 60. A higher value indicates a better pain reduction.	Up to 6 hours postdose
Number of Participants Required or Did Not Reqiure Rescue Pain Medication		Up to 12 hours postdose
Amount of Rescue Medication	To quantify the use of opioid analgesics in treatment of post-operative dental pain, the amount of rescue medications (opioids) was converted to a standard unit, which was Morphine Milligram Equivalent (MME) using below formula: MME/Day = Strength per Unit × (Number of units / Days supply) × MME conversion factor	Up to 12 hours postdose
Time to First Use of Rescue Medication	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 12 hours postdose
Duration of Pain at Least Half Gone Over 12 Hours		Up to 12 hours postdose
Duration of Pain at Least Half Gone Over 6 Hours		Up to 6 hours postdose

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Cooper SA, Desjardins PJ, Bertoch T, Paredes-Diaz A, Troullos E, Tajaddini A, Centofanti R, An R, Morella D. Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial. Postgrad Med. 2022 Jun;134(5):463-470. doi: 10.1080/00325481.2021.2008180. Epub 2021 Dec 8.

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2020
• Primary Completion (Actual): October 2, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Postsurgical Dental Pain
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; 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; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Gout Suppressants; Antitussive Agents; Acetaminophen; Naproxen; Hydrocodone; Acetaminophen, hydrocodone drug combination
• Other Study ID Numbers: 20536

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

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.: No