A Study of an Acetaminophen/Naproxen Sodium Fixed Combination, Acetaminophen and Naproxen Sodium in Postoperative Dental Pain

A Full-Factorial, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Dose Efficacy and Safety Study of an Acetaminophen/Naproxen Sodium Fixed Combination, Acetaminophen, and Naproxen Sodium in Postoperative Dental Pain

The purpose of this study is to evaluate how well a fixed combination of acetaminophen/naproxen sodium relieves postoperative dental pain compared with acetaminophen, naproxen sodium and placebo.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo; Drug: Acetaminophen/Naproxen Sodium Fixed Combination; Drug: Naproxen Sodium; Drug: Acetaminophen

Detailed Description

This is a randomized, double-blind, placebo-controlled, single-dose full-factorial study to evaluate the analgesic efficacy and safety of a fixed combination of acetaminophen and naproxen sodium, compared with acetaminophen or naproxen sodium alone, and placebo following surgical extraction of three or four third molars.

• Study Type: Interventional
• Enrollment (Actual): 447
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Weigh 100 pounds or greater and have a body mass index (BMI) of 17.5 to 30.4 (inclusive) at screening
• Surgical removal of three or four third molars, of which, two must be mandibular impactions
• Meets requirements for post-surgical pain level
• Females of childbearing potential and males agree to contraceptive requirements of study
• Have a negative urine drug screen at screening, and on day of surgical procedure

Exclusion Criteria:

• Pregnant female, breastfeeding, trying to become pregnant or male with pregnant partner or partner currently trying to become pregnant
• Have a known allergy or hypersensitivity to naproxen (or other NSAIDs including aspirin) or to acetaminophen, oxycodone or other opioids
• Not able to swallow whole large tablets or capsules
• History of any condition(s) in investigator's opinion, may jeopardize subject safety, well-being and integrity of study
• Use analgesics 5 or more times per week
• History of chronic tranquilizer use, heavy drinking, or substance abuse, as judged by the investigator site staff, in the last 5 years
• Use any immunosuppressive drugs within 2 weeks of surgical procedure
• History of endoscopically documented peptic ulcer disease or bleeding disorder in the last 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetaminophen/Naproxen Sodium Fixed Combination; Participants will receive a single oral dose of two Acetaminophen/Naproxen Sodium Fixed Combination tablets.	Drug: Acetaminophen/Naproxen Sodium Fixed Combination; Fixed combination of Acetaminophen/Naproxen Sodium will be administered orally.
Active Comparator: Naproxen Sodium; Participants will receive a single oral dose of one Naproxen Sodium tablet with one Placebo capsule.	Drug: Placebo; Placebo will be administered orally.; Drug: Naproxen Sodium; Naproxen Sodium will be administered orally.
Active Comparator: Acetaminophen; Participants will receive a single oral dose of two Acetaminophen tablets.	Drug: Acetaminophen; Acetaminophen will be administered orally.
Placebo Comparator: Placebo; Participants will receive a single oral dose of two Placebo capsules.	Drug: Placebo; Placebo will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Sum of Pain Intensity Difference from 0 to 12 Hours After Dosing (SPID 0-12)	Time-weighted sum of pain intensity difference (SPID) scores will be calculated using values collected on the Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain) collected at each scheduled timepoint within the specified timeframe.	0 to 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Sum of Pain Intensity Difference From 6 to 12 Hours (SPID 6-12)	Time-weighted sum of pain intensity difference (SPID) scores will be calculated using values collected on the PI-NRS ranging from 0-10 (0 = no pain, 10 = very severe pain) collected at each scheduled timepoint within the specified timeframe.	6 to 12 hours
Time to First Request of Rescue Analgesic	Time to first request for rescue medication will be measured as the elapsed time from when investigational product (IP) was given until the time rescue medication was first requested.	0 to 24 hours
Percentage of Participants who Request Rescue Analgesic During the First 12 hours	Percentage of participants who request rescue analgesic during the first 12 hours will be reported.	0 to 12 hours

Collaborators and Investigators

• Sponsor: Johnson & Johnson Consumer Inc. (J&JCI)
• Investigators: Principal Investigator: Todd Bertoch, JBR Clinical Research

Publications and helpful links

General Publications

• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.
• Cooper SA, Desjardins PJ, Turk DC, Dworkin RH, Katz NP, Kehlet H, Ballantyne JC, Burke LB, Carragee E, Cowan P, Croll S, Dionne RA, Farrar JT, Gilron I, Gordon DB, Iyengar S, Jay GW, Kalso EA, Kerns RD, McDermott MP, Raja SN, Rappaport BA, Rauschkolb C, Royal MA, Segerdahl M, Stauffer JW, Todd KH, Vanhove GF, Wallace MS, West C, White RE, Wu C. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain. 2016 Feb;157(2):288-301. doi: 10.1097/j.pain.0000000000000375.
• Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006 Apr;79(4):371-8. doi: 10.1016/j.clpt.2005.12.307.
• Cooper SA, Desjardins PJ. The value of the dental impaction pain model in drug development. Methods Mol Biol. 2010;617:175-90. doi: 10.1007/978-1-60327-323-7_15.
• GUZMAN F, BRAUN C, LIM RK, POTTER GD, RODGERS DW. NARCOTIC AND NON-NARCOTIC ANALGESICS WHICH BLOCK VISCERAL PAIN EVOKED BY INTRA-ARTERIAL INJECTION OF BRADYKININ AND OTHER ALGESIC AGENTS. Arch Int Pharmacodyn Ther. 1964 Jun 1;149:571-88. No abstract available.
• LIM RK, GUZMAN F, RODGERS DW, GOTO K, BRAUN C, DICKERSON GD, ENGLE RJ. SITE OF ACTION OF NARCOTIC AND NON-NARCOTIC ANALGESICS DETERMINED BY BLOCKING BRADYKININ-EVOKED VISCERAL PAIN. Arch Int Pharmacodyn Ther. 1964 Nov 1;152:25-58. No abstract available.
• Aronoff DM, Oates JA, Boutaud O. New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clin Pharmacol Ther. 2006 Jan;79(1):9-19. doi: 10.1016/j.clpt.2005.09.009. No abstract available.
• Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, Eschalier A. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain. 2008 Sep 30;139(1):190-200. doi: 10.1016/j.pain.2008.03.030. Epub 2008 May 15.
• Koch-Weser J. Drug therapy. Acetaminophen. N Engl J Med. 1976 Dec 2;295(23):1297-300. doi: 10.1056/NEJM197612022952306. No abstract available.
• Milton AS. Modern views on the pathogenesis of fever and the mode of action of antipyretic drugs. J Pharm Pharmacol. 1976 Apr;28(4 SUPPL):393-9. doi: 10.1111/j.2042-7158.1976.tb04186.x. No abstract available.
• Ameer B, Greenblatt DJ. Acetaminophen. Ann Intern Med. 1977 Aug;87(2):202-9. doi: 10.7326/0003-4819-87-2-202.
• Product Monograph for Aleve (Naproxen Sodium Tablets USP/Liquid Gels/Capsules 220 mg). Bayer Inc. Consumer Care. Revised 8 January 2015
• Todd PA, Clissold SP. Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states. Drugs. 1990 Jul;40(1):91-137. doi: 10.2165/00003495-199040010-00006.
• Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet. 1997 Apr;32(4):268-93. doi: 10.2165/00003088-199732040-00002.
• Lipkovich I, Ratitch B, O'Kelly M. Sensitivity to censored-at-random assumption in the analysis of time-to-event endpoints. Pharm Stat. 2016 May;15(3):216-29. doi: 10.1002/pst.1738. Epub 2016 Mar 21.
• Cheung R, Krishnaswami S, Kowalski K. Analgesic efficacy of celecoxib in postoperative oral surgery pain: a single-dose, two-center, randomized, double-blind, active- and placebo-controlled study. Clin Ther. 2007;29 Suppl:2498-510. doi: 10.1016/j.clinthera.2007.12.008.
• Fricke J, Davis N, Yu V, Krammer G. Lumiracoxib 400 mg compared with celecoxib 400 mg and placebo for treating pain following dental surgery: a randomized, controlled trial. J Pain. 2008 Jan;9(1):20-7. doi: 10.1016/j.jpain.2007.08.004. Epub 2007 Oct 15.
• Clinical Study Report CCSPAA001068. A randomized, double-blind, placebo- and activecontrolled, proof of concept study to evaluate two strengths of concomitantly dosed naproxen sodium with acetaminophen, compared with naproxen sodium, hydrocodone/acetaminophen and placebo in postoperative dental pain.: Johnson & Johnson Consumer, Inc., May 2019.
• Clinical Study Report CCSPAA002398. A Randomized, Double-blind, Placebo-controlled Study to Evaluate Five Strengths of a Fixed Combination of Acetaminophen/Naproxen Sodium in Postoperative Dental Pain.: Johnson & Johnson Consumer, Inc., November 2020.
• 21 CFR § 300.50 - Fixed-combination prescription drugs for humans, 40 FR 13496, Mar. 27, 1975, as amended at 64 FR 401, Jan. 5, 1999.
• Little RJ, Rubin DB. Statistical analysis with missing data: John Wiley & Sons; 2002.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Actual): May 17, 2024
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 9, 2023

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Pain; Acetaminophen; Analgesics; Dental Pain; Naproxen Sodium; Fixed-Dose
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Acetaminophen; Naproxen
• Other Study ID Numbers: CCSPAA005199 (Other Grant/Funding Number: Johnson & Johnson Consumer, Inc. (JJCI))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Johnson & Johnson Consumer Inc. has an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for evaluation of requests for clinical study reports and participant level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Requests for access to the study data can be submitted through the YODA Project site at http://yoda.yale.edu.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No