Study to Collect Information on How Well the Study Drug Naproxen Sodium Tablets Works Compared to Hydrocodone/Acetaminophen Tablets in Order to Relieve Pain in Participants Experiencing Moderate to Severe Pain After Having Their Wisdom Teeth Removed

Study Overview
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Brief Summary
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With this study researchers want to collect information on how long the pain relief lasts after a fixed dose of naproxen sodium or hydrocodone/acetaminophen or placebo (contains no medication) over 12 hours in subjects experiencing moderate to severe pain after having their wisdom teeth removed. Naproxen Sodium (Aleve®) is a drug that is used for the temporary relief of minor aches and pains. Hydrocodone/Acetaminophen is a combination drug used to relieve moderate to severe pain. It contains an opioid (narcotic) pain reliever (hydrocodone) and a non-opioid pain reliever (acetaminophen).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial to Compare the Analgesic Efficacy and Safety of Naproxen Sodium Tablets and Hydrocodone/Acetaminophen Tablets in Postsurgical Dental Pain

Conditions
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Pain

Intervention / Treatment
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* Drug: Naproxen Sodium (Aleve, BAY117031)
* Drug: Hydrocodone/Acetaminophen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, ambulatory, male or female volunteers 18 to 40 years of age; Subjects will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios: two full bony impactions two partial bony impactions one full bony impaction in combination with one partial bony impaction Supernumerary teeth present may also be removed at the discretion of the oral surgeon; Have not consumed alcoholic beverages, or foods and beverages containing caffeine (examples; coffee, tea, chocolate, and colas) after midnight prior to surgery and agree not to consume any of these foods or beverages throughout their stay at the study site; Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator; Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity NRS within 4.5 hours postsurgery; Ability to understand and follow study-related instructions; Be willing and able to participate in all scheduled visits, treatment plan, and trial procedures according to the clinical protocol; Exclusion Criteria: History of hypersensitivity to naproxen sodium, hydrocodone/acetaminophen, ibuprofen, NSAIDS, aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational products; Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years; Subjects with the following medical conditions may be eligible at the discretion of the investigator: ADHD on a stable dose regimen of methylphenidate/(dextro)amphetamine for at least 6 months; subjects with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months; Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months; Use of any OTC or prescription medications with which the administration of naproxen, hydrocodone/acetaminophen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated; Females who are planning to become pregnant, pregnant or lactating; Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years); Alcoholism or drug abuse within 2 years prior to the Screening Visit or routine consumption of 3 or more alcohol containing beverages per day; Alcohol containing beverages are defined as one beer (5%), one glass of wine (11%) and one shot (40%) hard liquor; Surgeon's trauma rating of severe following surgery; Unwilling or unable to comply with all requirements outlined in the protocol;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naproxen sodium<br>After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1) | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* 220 mg per tablet, two tablets (440 mg), intake a single dose orally.<br>|
| Active Comparator: Hydrocodone/Acetaminophen<br>After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1) | Drug: Hydrocodone/Acetaminophen<br>* 5/325 mg per tablet, two tablets (10/650 mg), intake a single dose orally.<br>|
| Placebo Comparator: Placebo<br>After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1) | Drug: Placebo<br>* two tablets, intake a single dose orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference Over 12 Hours (SPID 0-12) | Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 12 hours ranges from -120 to 120. A higher value indicates a better pain reduction. | Up to 12 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Pain Relief Over 12 Hours (TOTPAR 0-12) | Pain relief is measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief). Total Pain Relief is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 12 hours ranges from 0 to 48, a higher value indicates more pain relief. | Up to 12 hours postdose | 
| Total Pain Relief Over 6 Hours (TOTPAR 0-6) | Pain relief is measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief). Total Pain Relief is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 6 hours ranges from 0 to 24, a higher value indicates more pain relief. | Up to 6 hours postdose | 
| Sum of Pain Intensity Difference Over 6 Hours (SPID 0-6) | Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 6 hours ranges from -60 to 60. A higher value indicates a better pain reduction. | Up to 6 hours postdose | 
| Number of Participants Required or Did Not Reqiure Rescue Pain Medication |  | Up to 12 hours postdose | 
| Amount of Rescue Medication | To quantify the use of opioid analgesics in treatment of post-operative dental pain, the amount of rescue medications (opioids) was converted to a standard unit, which was Morphine Milligram Equivalent (MME) using below formula: MME/Day = Strength per Unit × (Number of units / Days supply) × MME conversion factor | Up to 12 hours postdose | 
| Time to First Use of Rescue Medication | If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment. | Up to 12 hours postdose | 
| Duration of Pain at Least Half Gone Over 12 Hours |  | Up to 12 hours postdose | 
| Duration of Pain at Least Half Gone Over 6 Hours |  | Up to 6 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postsurgical Dental Pain