Naproxen Sodium/Acetaminophen Proof of Concept Dosing Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pain

Intervention / Treatment
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* 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


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

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Post-operative dental pain following third molar extraction.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 440 mg naproxen sodium with 1000 mg acetaminophen<br>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<br>* 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<br>* Other names: Naproxen Sodium with Acetaminophen - High Dose;|
| Experimental: 220 mg naproxen sodium with 650 mg acetaminophen<br>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<br>* 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<br>* Other names: Naproxen Sodium with Acetaminophen - Low Dose;|
| Active Comparator: 10 mg hydrocodone + 650 mg acetaminophen<br>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<br>* 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<br>* Other names: Commercial Hydrocodone + Acetaminophen Tablet;|
| Active Comparator: 440 mg naproxen sodium<br>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<br>* 440 mg naproxen sodium administered as a single dose of two naproxen sodium 220 mg tablets and two placebo tablets<br>* Other names: Naproxen sodium;|
| Placebo Comparator: Placebo tablet<br>Single dose of four placebo tablets | Drug: Placebo tablet<br>* Single dose of four placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 6 Hours (SPID 0-6) | Time-weighted sum of the pain intensity difference (SPID) score was measured using a Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-6 hours was from -60 to 60. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment. Time-weighted sum of the pain intensity difference 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 0 to 6 hours. | Baseline (0 hour) up to 6 hours post-dose | 
| 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 score was measured using a PI-NRS ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-12 hours was from -120 to 120. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment (12 hours). Time-weighted sum of the pain intensity difference 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 0 to 12 hours. | Baseline (0 hour) up to 12 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 6 Hours (TOTPAR 0-6) | Time-weighted total pain relief (TOTPAR) was measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0-10 (0 = no relief, 10 = 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. The minimum value was 0, and the maximum value was 60. Higher scores was indicative of more pain relief. | Baseline (0 hour) up to 6 hours post-dose | 
| Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 8 Hours (TOTPAR 0-8) | TOTPAR was measured using a PR-NRS ranging from 0-10 (0 = no relief, 10 = 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. The minimum value was 0, and the maximum value was 80. Higher scores was indicative of more pain relief. | Baseline (0 hour) up to 8 hours post-dose | 
| Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 12 Hours (TOTPAR 0-12) | TOTPAR was measured using a PR-NRS ranging from 0-10 (0 = no relief, 10 = 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. The minimum value was 0, and the maximum value was 120. Higher scores was indicative of more pain relief. | Baseline (0 hour) up to 12 hours post-dose | 
| Time-Weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 8 Hours (SPID 0-8) | Time-weighted sum of the pain intensity difference score was measured using a PI-NRS ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-8 hours was from -80 to 80. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment (8 hours). Time-weighted sum of the pain intensity difference 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 0 to 8 hours. | Baseline (0 hour) up to 8 hours post-dose | 
| Pain Relief (PAR) Scores at Individual Timepoints | Participants answered a question at individual time points: how much relief do you have from your starting pain? on a 11-point PR-NRS. Scale ranged from 0=no relief to 10=complete relief. Higher score indicated improvement in pain. | 0.25 hours, 0.5 hours, 0.75 hours, 1 hours, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours | 
| Pain Intensity Difference (PID) Scores at Individual Time Points | Pain Intensity was self-reported over 12 hours, using a pain rating of 0-10 on the PI-NRS, with score ranged from 0-10 (0= no pain; 10 = worst imaginable pain). Pain intensity differences were calculated with respect to baseline at each time point after study drug administration. | 0.25 hours, 0.5 hours, 0.75 hours, 1 hours, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours | 
| Participant's Global Evaluation of Study Medication OR Overall Impression of Study Medication According to Participant's Global Evaluation | Participants were asked to rate their overall impression of the study medication using the following scale: poor (0), fair (1), good (2), very good (3), and excellent (4) where higher score represented better outcome. | Up to 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesics, Dental Pain, Naproxen, Acetaminophen, Pain