Evaluate Analgesic/Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain

Study Overview
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Brief Summary
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The objective of the study is to evaluate the efficacy and safety of a single oral dose of two dose combinations of naproxen sodium and diphenhydramine (DPH) to demonstrate that naproxen sodium/DPH combination provides added clinical benefit to sleep improvement than either single ingredient alone in subjects with post-surgical dental pain and phase advanced sleep.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel Group Trial Assessing the Efficacy of Naproxen Sodium and Diphenhydramine Combination in Postsurgical Dental Pain With Phase Advanced Sleep

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111)
* Drug: Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111)
* Drug: Naproxen sodium 440 mg (BAYH6689)
* Drug: DPH 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, ambulatory, male and female volunteers ages 12 and older Scheduled to undergo surgical removal of a minimum of two third molars of which at least one has to be a mandibular third molar. The mandibular extraction(s) required by each subject must meet one of the following scenarios: one full bony impaction two partial bony impactions one full bony impaction and one partial bony impaction one full bony impaction and one soft tissue impaction one full bony impaction and one erupted third molar. Two full bony mandibular impactions are not allowed. Maxillary third molars may be removed regardless of impaction level. Have moderate to severe postoperative pain on the Categorical Pain Rating Scale and a score of ≥ 50 mm on the 100-mm visual analog Pain Severity Rating Scale between 1600 hour and 1830 hour on the day of surgery Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, Depo-Provera, or double-barrier and have a negative pregnancy test at Screening and prior to surgery. Female subjects of nonchildbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy Provide a personally signed and dated informed consent indicating that the subject has been informed of all pertinent aspects of the trial, (subjects <18 years of age must sign a written assent and have parental or guardian consent). Exclusion Criteria: History of hypersensitivity to naproxen, diphenhydramine, nonsteroidal anti-inflammatory drug (NSAIDS), tramadol, aspirin or any other antihistamine and similar pharmacological agents or components of the products Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years Relevant concomitant disease such as asthma (exercise induced asthma is permitted), chronic sinusitis or nasal structural abnormalities causing greater than 50 percent obstruction (polyposis nasi, marked septal deviation) that can interfere with the conduct of the study in the judgment of the investigator Current or past history of bleeding disorder(s) Acute illness or local infection prior to surgery that can interfere with the conduct of the study in the judgment of the investigator Chronic use of antihistamines defined as using 5 or more times a week for 2 or more consecutive weeks during the past 3 months Positive alcohol breathalyzer test and positive urine drug test prior to surgery Females who are pregnant or lactating Chronic or severe sleep problems that do not respond to / Over the Counter (OTC) medication and requires a prescription hypnotic or sedative Habitually spends less than 6.5 hours in bed

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111)<br> | Drug: Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111)<br>* Participants received two Naproxen sodium 220 mg / DPH (Diphenhydramine hydrochloride) 25 mg tablets orally, single dose<br>|
| Experimental: Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111)<br> | Drug: Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111)<br>* Participants received one Naproxen sodium 220 mg / DPH 50 mg tablet and one matching placebo capsule orally, single dose<br>|
| Active Comparator: Naproxen sodium 440 mg (BAYH6689)<br> | Drug: Naproxen sodium 440 mg (BAYH6689)<br>* Participants received two Naproxen sodium 220 mg tablets orally, single dose<br>|
| Active Comparator: DPH 50 mg<br> | Drug: DPH 50 mg<br>* Participants received two DPH (Diphenhydramine hydrochloride) 25mg tablets orally, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake Time After Sleep Onset (WASO) Measured by Actigraphy | WASO was defined as Total wake time (in minutes) after sleep onset during the 10 hours in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects. | Up to 10 hours | 
| Sleep Latency Measured by Actigraphy | Sleep latency was defined as the time to sleep onset from the time of dosing as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects. | Up to 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Sleep Time Measured by Actigraphy | Total time time was measured as total time spent sleeping (not to exceed 600 minutes) during the in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects. | Up to 10 hours | 
| Sleep Efficiency Measured by Actigraphy | Sleep efficiency was calculated as (total sleep time/total time in-bed time) × 100; total in-bed time was fixed at 10 hours. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects. | Up to 10 hours | 
| Global Assessment of Investigational Product as a Sleep Aid | The Global Assessment of Investigational Product as a Sleep-Aid was rated using a 5-point categorical scale for which the potential response was poor (0), fair, (1), good (2), very good (3), or excellent (4). | Up to 10 hours | 
| Karolinska Sleep Diary - Sleep Quality | Subjects responded to the following question: How was your sleep? very poor (1); rather poor (2); neither poor nor good (3); rather good (4); very good (5) | Up to 10 hours | 
| Karolinska Sleep Diary - Calmness of Sleep | Subjects responded to the following question: How calm was your sleep? very restless (1); rather restless (2); neither restless nor calm (3); rather calm (4); very calm (5) | Up to 10 hours | 
| Karolinska Sleep Diary - Easiness to Fall Asleep | Subjects responded to the following question: How easy was it to fall asleep? very difficult (1); rather difficult (2); neither difficult nor easy (3); rather easy (4); very easy (5) | Up to 10 hours | 
| Karolinska Sleep Diary - Premature Awakening | Subjects responded to the following question: Premature awakening? woke up much too early (1); woke up somewhat too early (2); no (3) | Up to 10 hours | 
| Karolinska Sleep Diary - Ease of Awakening | Subjects responded to the following question: Ease of awakening? (1) very difficult; (2) rather difficult; (3) neither difficult nor easy; (4) rather easy; very easy (5) | Up to 10 hours | 
| Karolinska Sleep Diary - Well Rested | Subjects responded to the following question: Well Rested? not rested at all (1); somewhat unrested (2); completely rested (3) | Up to 10 hours | 
| Karolinska Sleep Diary - Sufficient Sleep | Subjects responded to the following question: Did you get enough (sufficient) sleep? no, definitely too little (1); no, much too little (2); no, somewhat too little (3); yes, almost enough (4); yes, definitely enough (5) | Up to 10 hours | 
| Subjective Sleep Questionnaire - Quality of Your Sleep Last Night | Subjects responded to Quality of sleep (10-point scale, where 1 was poor and 10 was excellent) | Up to 10 hours | 
| Subjective Sleep Questionnaire - Refreshing Nature of Your Sleep Last Night | Subjects responded to Refreshing nature of sleep (10-point scale, where 1 was not refreshing and 10 was very refreshing) | Up to 10 hours | 
| Subjective Sleep Questionnaire - Time to Fall Asleep Last Night | Subjects responded to Estimate of how long it took to fall asleep (minutes) | Up to 10 hours | 
| Subjective Sleep Questionnaire - Number of Minutes You Think That You Were Awake From the Time You Fell Asleep Until the Time You Got Out of Bed | Subjects responded to Estimate of the amount of time the subject was awake from the time he or she fell asleep until the time he or she got out of bed (hours and minutes) | Up to 10 hours | 
| Change From Baseline in Pain Intensity | Pain Severity was collected on a 4-point categorical scale: 0=no pain, 1=mild pain, 2=moderate pain, 4=severe pain | Baseline and up to 10 hours | 
| Overall Rating of Pain Relief | The Pain Relief Rating Scale was a 5-point categorical scale which included the following possible responses to the request to finish statement Overall, the relief from my starting pain was: no relief (0); a little relief (1); some relief (2); a lot of relief (3); complete relief (4). | Up to 10 hours | 
| Time to Rescue Medication | If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded | Up to 10 hours | 
| Cumulative Proportion of Subjects Taking Rescue Medication by Hour | If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded | Up to 10 hours | 
| Global Assessment of Investigational Product as a Pain Reliever | The Global Assessment of Investigational Product as a Pain Reliever was a 5- point categorical scale which included the following possible responses: poor (0); fair (1); good (2); very good (3); excellent (4). | Up to 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Naproxen sodium, Diphenhydramine