Acetaminophen/Naproxen Sodium Dose Ranging Study

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Five Strengths of a Fixed Combination of Acetaminophen/Naproxen Sodium in Postoperative Dental Pain

Study assessing the relative efficacy of five strengths of a fixed combination of acetaminophen and naproxen sodium is being investigated to help inform selection of dose(s) for further development and to evaluate the safety of a fixed combination of naproxen sodium and acetaminophen.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Acetaminophen/naproxen sodium Dose A; Drug: Acetaminophen/naproxen sodium Dose B; Drug: Acetaminophen/naproxen sodium Dose C; Drug: Acetaminophen/naproxen sodium Dose D; Drug: Acetaminophen/naproxen sodium Dose E; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled study to evaluate the analgesic efficacy and safety profile of the following doses of a fixed combination of Acetaminophen (APAP)/Naproxen sodium (NPX) administered as a single two-tablet dose:[Acetaminophen/Naproxen Sodium Dose A, Acetaminophen/Naproxen Sodium Dose B, Acetaminophen/Naproxen Sodium Dose C, Acetaminophen/Naproxen Sodium Dose D, Acetaminophen/Naproxen Sodium Dose E and Placebo] following surgical extraction of four third molars.

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 2

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: 17 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females 17-50 years old
2. Weigh 100 pounds or greater and have a body mass index (BMI) of 17.5-35.4 (inclusive) at screening
3. Surgical removal of three or four third molars, of which, two must be mandibular impactions
4. Meets requirements for post-surgical pain level
5. Females of childbearing potential and males agree to contraceptive requirements of study
6. Have a negative urine drug screen at screening, and on day of surgical procedure

Exclusion Criteria:

1. Pregnant female, breastfeeding, trying to become pregnant or male with pregnant partner or partner currently trying to become pregnant
2. Have a known allergy or hypersensitivity to naproxen or other NSAIDs, including aspirin, or to acetaminophen, oxycodone or other opioids;
3. Not able to swallow whole large tablets or capsules
4. History of any condition (s) in investigator's opinion, may jeopardize subject safety, well-being and integrity of study
5. Use analgesics 5 or more times per week
6. History of chronic tranquilizer use, heavy drinking, or substance abuse, as judged by the investigator site staff, in the last 5 years
7. Use of any immunosuppressive drugs within 2 weeks of screening
8. 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: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetaminophen/naproxen sodium Dose A; Acetaminophen/naproxen sodium Dose A administered as a single two-tablet dose.	Drug: Acetaminophen/naproxen sodium Dose A; Acetaminophen/naproxen sodium Dose A administered as a single two-tablet dose.
Experimental: Acetaminophen/naproxen sodium Dose B; Acetaminophen/naproxen sodium Dose B administered as a single two-tablet dose.	Drug: Acetaminophen/naproxen sodium Dose B; Acetaminophen/naproxen sodium Dose B administered as a single two-tablet dose.
Experimental: Acetaminophen/naproxen sodium Dose C; Acetaminophen/naproxen sodium Dose C administered as a single two-tablet dose.	Drug: Acetaminophen/naproxen sodium Dose C; Acetaminophen/naproxen sodium Dose C administered as a single two-tablet dose.
Experimental: Acetaminophen/naproxen sodium Dose D; Acetaminophen/naproxen sodium Dose D administered as a single two-tablet dose.	Drug: Acetaminophen/naproxen sodium Dose D; Acetaminophen/naproxen sodium Dose D administered as a single two-tablet dose.
Experimental: Acetaminophen/naproxen sodium Dose E; Acetaminophen/naproxen sodium Dose E administered as a single two-tablet dose.	Drug: Acetaminophen/naproxen sodium Dose E; Acetaminophen/naproxen sodium Dose E administered as a single two-tablet dose.
Placebo Comparator: Placebo; Placebo tablets administered as a single two-tablet dose.	Drug: Placebo; Placebo tablets administered as a single two-tablet dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 12 Hours (SPID 0-12)	Time weighted sum of the pain intensity difference (SPID) score is derived from pain intensity difference (PID) score. Pain intensity-numerical rating scale (PI-NRS) was used to assess pain intensity on scale ranged from 0 (no pain) to 10 (very severe pain), higher score indicated severe pain intensity. PID score was the difference between baseline pain intensity and pain intensity at assessment timepoint (12 hours). The SPID scores were derived by first multiplying each PID score by the time from the previous time point and adding these time weighted PID scores together over the interval from 0 to 12 hours. The possible range of SPID for 0 to 12 hours was from -120 to 120. A higher value of SPID indicated greater pain relief.	Baseline (0 hour) up to 12 hours post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 12 Hours (TOTPAR 0-12)	Time weighted total pain relief (TOTPAR) was measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0 to10 (0 = no relief, 10 = complete relief). A higher score indicated greater pain relief. Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value was 0, and the maximum value was 120. Higher scores were indicative of more pain relief.	Baseline (0 hour) up to 12 hours post-dose on Day 1
Time Weighted Sum of Pain Intensity Difference Score From 6 Hours to 12 Hours (SPID 6-12)	Time weighted sum of the pain intensity difference (SPID) score is derived from PID score. PI-NRS was used to assess pain intensity on scale ranged from 0 (no pain) to 10 (very severe pain), higher score indicated severe pain intensity. PID was the difference between pain intensity at 6 hours and pain intensity at assessment timepoint (12 hours). The SPID scores were derived by first multiplying each PID score by the time from the previous time point and adding these time weighted PID scores together over the intervals from 6 to 12 hours (6 hours). The possible range of SPID for 6 to12 hours was from -60 to 60. A higher value of SPID indicated greater pain relief.	From 6 hours up to 12 hours post-dose on Day 1
Time to First Use of Rescue Analgesic Medication	Time to first use of rescue analgesic medication was measured as the elapsed time (in minutes) from when the investigational product was given until the time rescue analgesic was first given. Participants who did not use rescue medication during the 24 hour study period had their time to rescue set to 24 hours and were censored at 24 hours. Kaplan-Meier method was used for the analysis.	From 0 minute up to 1440 minutes post-dose (that is, up to 24 hours post-dose) on Day 1
Proportion of Participants Who Required Rescue Analgesic Medication	Proportion (cumulative data) of participants who used rescue analgesic medication through 24 hours post study drug administration on Day 1 which was assessed by using Kaplan-Meier estimates were reported.	From 0 hour up to 24 hours post-dose on Day 1

Collaborators and Investigators

• Sponsor: Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
• Investigators: Principal Investigator: Todd Bertoch, MD, JBR Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Actual): April 9, 2021
• Study Completion (Actual): May 3, 2021

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pain; Acetaminophen; Analgesics; Dental Pain; Naproxen Sodium; Fixed-Dose
• Additional Relevant MeSH Terms: 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: CCSPAA002398

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