Naproxen Sodium/Acetaminophen Proof of Concept Dosing Study

• ClinicalTrials.gov Identifier: NCT03879408
• Recruitment Status: Completed
• First Posted: March 18, 2019
• Last Update Posted: November 23, 2020
• Sponsor: Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
• Information provided by (Responsible Party): Johnson & Johnson Consumer and Personal Products Worldwide ( Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division )

Study Description

Brief Summary:

Study assessing efficacy and safety of concomitantly dosed naproxen sodium with acetaminophen, compared with naproxen sodium, hydrocodone/acetaminophen and Placebo in a postoperative dental pain.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: 440 mg naproxen sodium with 1000 mg acetaminophen; Drug: 220 mg naproxen sodium with 650 mg acetaminophen; Drug: 10 mg hydrocodone + 650 mg acetaminophen; Drug: 440 mg naproxen sodium; Drug: Placebo tablet	Phase 2

Detailed Description:

This is a randomized, double-blind, placebo- and active-controlled, parallel-group study to evaluate the analgesic efficacy and safety of concomitantly administered naproxen sodium 440 mg with acetaminophen 1000 mg and concomitantly administered naproxen sodium 220 mg with acetaminophen 650 mg, compared with a fixed combination of hydrocodone 10 mg/acetaminophen 650 mg, naproxen sodium 440 mg, and placebo over a twelve-hour period after surgical extraction of four third molars.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 290 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Post-operative dental pain following third molar extraction.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Placebo And Active Controlled, Study To Evaluate Two Strengths Of Concomitantly Dosed Naproxen Sodium With Acetaminophen, Compared With Naproxen Sodium and Hydrocodone/Acetaminophen In Postoperative Dental Pain
• Actual Study Start Date: May 28, 2019
• Actual Primary Completion Date: November 7, 2019
• Actual Study Completion Date: November 13, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 440 mg naproxen sodium with 1000 mg acetaminophen; 440 mg naproxen sodium with 1000 mg acetaminophen administered as a single dose of two naproxen sodium 220 mg tablets and two acetaminophen 500 mg tablets	Drug: 440 mg naproxen sodium with 1000 mg acetaminophen; 440 mg naproxen sodium with 1000 mg acetaminophen administered as a single dose of two naproxen sodium 220 mg tablets and two acetaminophen 500 mg tablets; Other Name: Naproxen Sodium with Acetaminophen - High Dose
Experimental: 220 mg naproxen sodium with 650 mg acetaminophen; 220 mg naproxen sodium with 650 mg acetaminophen administered as a single dose of one naproxen sodium 220 mg tablet and two acetaminophen 325 mg tablets and one placebo tablet	Drug: 220 mg naproxen sodium with 650 mg acetaminophen; 220 mg naproxen sodium with 650 mg acetaminophen administered as a single dose of one naproxen sodium 220 mg tablet and two acetaminophen 325 mg tablets and one placebo tablet; Other Name: Naproxen Sodium with Acetaminophen - Low Dose
Active Comparator: 10 mg hydrocodone + 650 mg acetaminophen; 10 mg hydrocodone + 650 mg acetaminophen administered as a single dose of two hydrocodone 5 mg + acetaminophen 325 mg tablets and two placebo tablets	Drug: 10 mg hydrocodone + 650 mg acetaminophen; 10 mg hydrocodone with 650 mg acetaminophen administered as a single dose of two hydrocodone 5 mg + acetaminophen 325 mg tablets and two placebo tablets; Other Name: Commercial Hydrocodone + Acetaminophen Tablet
Active Comparator: 440 mg naproxen sodium; 440 mg naproxen sodium administered as a single dose of two naproxen sodium 220 mg tablets and two placebo tablets	Drug: 440 mg naproxen sodium; 440 mg naproxen sodium administered as a single dose of two naproxen sodium 220 mg tablets and two placebo tablets; Other Name: Naproxen sodium
Placebo Comparator: Placebo tablet; Single dose of four placebo tablets	Drug: Placebo tablet; Single dose of four placebo tablets

Outcome Measures

Primary Outcome Measures :

1. Time Weighted Sum of Pain Intensity Difference from 0 to 6 hours (SPID 6) [ Time Frame: 0 to 6 hours ]
   Time-weighted sum of the pain intensity difference scores (SPID) will be measured using a Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).
2. Time Weighted Sum of Pain Intensity Difference from 0 to 12 hours (SPID 12) [ Time Frame: 0 to 12 hours ]
   Time-weighted sum of the pain intensity difference scores (SPID) will be measured using a Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).

Secondary Outcome Measures :

1. Time Weighted Total Pain Relief from 0 to 6 hours (TOTPAR 6) [ Time Frame: 0 to 6 hours ]
   Time-weighted total pain relief (TOTPAR) will be measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0-10 (0 = no relief, 10 = complete relief) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).
2. Time Weighted Total Pain Relief from 0 to 8 hours (TOTPAR 8) [ Time Frame: 0 to 8 hours ]
   Time-weighted total pain relief (TOTPAR) will be measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0-10 (0 = no relief, 10 = complete relief) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).
3. Time Weighted Total Pain Relief from 0 to 12 hours (TOTPAR 12) [ Time Frame: 0 to 12 hours ]
   Time-weighted total pain relief (TOTPAR) will be measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0-10 (0 = no relief, 10 = complete relief) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).
4. Time Weighted Sum of Pain Intensity Difference from 0 to 8 hours (SPID 8) [ Time Frame: 0 to 8 hours ]
   Time-weighted sum of the pain intensity difference scores (SPID) will be measured using a Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain) and will be collected at baseline, at each scheduled time point, at time of rescue (if applicable), and at time of perceptible and meaningful pain relief (if applicable).
5. Pain Relief (PAR) scores at 0.25 hours [ Time Frame: 0.25 hours ]
   Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
6. Pain Relief (PAR) scores at 0.5 hours [ Time Frame: 0.5 hours ]
   Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
7. Pain Relief (PAR) scores at 0.75 hours [ Time Frame: 0.75 hours ]
   Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
8. Pain Relief (PAR) scores at 1 hour [ Time Frame: 1 hour ]
   Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
9. Pain Relief (PAR) scores at 1.25 hours [ Time Frame: 1.25 hours ]
   Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
10. Pain Relief (PAR) scores at 1.5 hours [ Time Frame: 1.5 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
11. Pain Relief (PAR) scores at 2 hours [ Time Frame: 2 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
12. Pain relief (PAR) scores at 3 hours [ Time Frame: 3 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
13. Pain Relief (PAR) scores at 4 hours [ Time Frame: 4 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
14. Pain Relief (PAR) scores at 5 hours [ Time Frame: 5 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
15. Pain Relief (PAR) scores at 6 hours [ Time Frame: 6 hours ]
    Pain Relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
16. Pain Relief (PAR) scores at 7 hours [ Time Frame: 7 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
17. Pain Relief (PAR) scores at 8 hours [ Time Frame: 8 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
18. Pain Relief (PAR) scores at 9 hours [ Time Frame: 9 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
19. Pain Relief (PAR) scores at 10 hours [ Time Frame: 10 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
20. Pain Relief (PAR) scores at 11 hours [ Time Frame: 11 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
21. Pain Relief (PAR) scores at 12 hours [ Time Frame: 12 hours ]
    Pain relief (PAR) scores will be measured using a 0-10 Numerical Rating Scale (0 = no relief, 10 = complete relief) at individual time points.
22. Pain Intensity Difference (PID) scores at 0.25 hours [ Time Frame: 0.25 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
23. Pain Intensity Difference (PID) scores at 0.5 hours [ Time Frame: 0.5 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
24. Pain Intensity Difference (PID) scores at 0.75 hours [ Time Frame: 0.75 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
25. Pain Intensity Difference (PID) scores at 1 hour [ Time Frame: 1 hour ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
26. Pain Intensity Difference (PID) scores at 1.25 hours [ Time Frame: 1.25 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
27. Pain Intensity Difference (PID) scores at 1.5 hours [ Time Frame: 1.5 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
28. Pain Intensity Difference (PID) scores at 2 hours [ Time Frame: 2 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
29. Pain Intensity Difference (PID) scores at 3 hours [ Time Frame: 3 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
30. Pain Intensity Difference (PID) scores at 4 hours [ Time Frame: 4 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
31. Pain Intensity Difference (PID) scores at 5 hours [ Time Frame: 5 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
32. Pain Intensity Difference (PID) scores at 6 hours [ Time Frame: 6 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
33. Pain Intensity Difference (PID) scores at 7 hours [ Time Frame: 7 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
34. Pain Intensity Difference (PID) scores at 8 hours [ Time Frame: 8 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
35. Pain Intensity Difference (PID) scores at 9 hours [ Time Frame: 9 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
36. Pain Intensity Difference (PID) scores at 10 hours [ Time Frame: 10 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
37. Pain Intensity Difference (PID) scores at 11 hours [ Time Frame: 11 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
38. Pain Intensity Difference (PID) scores at 12 hours [ Time Frame: 12 hours ]
    Pain intensity difference (PID) Scores will be measured using a 0-10 Numerical Rating Scale (0 = no pain, 10 = very severe pain) at individual time points.
39. Subject Global Evaluation at 12 hours or rescue, whichever occurs first [ Time Frame: 12 hours or time of rescue medication, whichever occurs first ]
    Self-reported pain relief. Subject global evaluation of the investigational product will be collected at hour 12, at the time of rescue medication, or at the time of subject withdrawal with a 0-4 rating scale: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent.

Eligibility Criteria

• Ages Eligible for Study: 17 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Males of females 17-50 years old
2. Weigh 100 pounds or greater and have a body mass index (BMI) of 18.5 to 35 (inclusive) at screening
3. Surgical removal of up to 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 known allergy or hypersensitivity to naproxen or other NSAIDS, including aspirin, or to acetaminophen, tramadol, hydrocodone or other opioids
3. Not able to swallow 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, substance abuse as judged by investigator site staff within last 5 years
7. Use of immunosuppressive drugs within 2 weeks of screening
8. History of peptic ulcer disease or gastrointestinal bleeding in the last two years or hematologic bleeding

Contacts and Locations

Locations

United States, Utah

Jean Brown Research Clinical Research

Salt Lake City, Utah, United States, 84107

Sponsors and Collaborators

Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division

Investigators

• Principal Investigator: Todd Bertoch, MD; Jean Brown Research (JBR)

More Information

• Responsible Party: Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
• ClinicalTrials.gov Identifier: NCT03879408
• Other Study ID Numbers: CCSPAA001068
• First Posted: March 18, 2019
• Last Update Posted: November 23, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: http://yoda.yale.edu

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johnson & Johnson Consumer and Personal Products Worldwide ( Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division ):

Analgesics; Dental Pain; Naproxen; Acetaminophen; Pain

Additional relevant MeSH terms:

Acetaminophen; Naproxen; Acetaminophen, hydrocodone drug combination; Hydrocodone; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Gout Suppressants; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Antitussive Agents; Respiratory System Agents