Acetaminophen/Naproxen Sodium Dose Ranging Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 17-50 years old Weigh 100 pounds or greater and have a body mass index (BMI) of 17.5-35.4 (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 of any immunosuppressive drugs within 2 weeks of screening History of endoscopically documented peptic ulcer disease or bleeding disorder in the last 2 years

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: Acetaminophen/naproxen sodium Dose A<br>Acetaminophen/naproxen sodium Dose A administered as a single two-tablet dose. | Drug: Acetaminophen/naproxen sodium Dose A<br>* Acetaminophen/naproxen sodium Dose A administered as a single two-tablet dose.<br>|
| Experimental: Acetaminophen/naproxen sodium Dose B<br>Acetaminophen/naproxen sodium Dose B administered as a single two-tablet dose. | Drug: Acetaminophen/naproxen sodium Dose B<br>* Acetaminophen/naproxen sodium Dose B administered as a single two-tablet dose.<br>|
| Experimental: Acetaminophen/naproxen sodium Dose C<br>Acetaminophen/naproxen sodium Dose C administered as a single two-tablet dose. | Drug: Acetaminophen/naproxen sodium Dose C<br>* Acetaminophen/naproxen sodium Dose C administered as a single two-tablet dose.<br>|
| Experimental: Acetaminophen/naproxen sodium Dose D<br>Acetaminophen/naproxen sodium Dose D administered as a single two-tablet dose. | Drug: Acetaminophen/naproxen sodium Dose D<br>* Acetaminophen/naproxen sodium Dose D administered as a single two-tablet dose.<br>|
| Experimental: Acetaminophen/naproxen sodium Dose E<br>Acetaminophen/naproxen sodium Dose E administered as a single two-tablet dose. | Drug: Acetaminophen/naproxen sodium Dose E<br>* Acetaminophen/naproxen sodium Dose E administered as a single two-tablet dose.<br>|
| Placebo Comparator: Placebo<br>Placebo tablets administered as a single two-tablet dose. | Drug: Placebo<br>* Placebo tablets administered as a single two-tablet dose.<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 from 0 to 12 hours after dosing (SPID 0-12) | Time-weighted sum of the pain intensity difference scores (SPID) will be calculated using values collected on the pain intensity Numerical Rating Scale 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 Relief from 0 to 12 hours (TOTPAR 0-12) | Time-weighted sum of the pain relief scores (TOTPAR) will be calculated using values collected on the pain relief Numerical Rating Scale ranging from 0-10 (0= no relief, 10= complete relief) collected at each scheduled timepoint within the specified timeframe. | 0 to 12 hours | 
| Time weighted sum of pain intensity difference from 6 to 12 hours (SPID 6-12) | Time-weighted sum of the pain intensity difference scores (SPID) will be calculated using values collected on the pain intensity Numerical Rating Scale 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 use of rescue analgesic |  | 0 to 24 hours | 

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