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

Pain, Postoperative Clinical Trial

— Morpheus II  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280591
• Other study ID #: 14837
• Status: Completed
• Phase: Phase 3
• First received: January 20, 2011
• Last updated: May 13, 2015
• Start date: October 2010
• Est. completion date: February 2011

Study information

• Verified date: May 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 712
• Est. completion date: February 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111)
Participants received two Naproxen sodium 220 mg / DPH (Diphenhydramine hydrochloride) 25 mg tablets orally, single dose
• Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111)
Participants received one Naproxen sodium 220 mg / DPH 50 mg tablet and one matching placebo capsule orally, single dose
• Naproxen sodium 440 mg (BAYH6689)
Participants received two Naproxen sodium 220 mg tablets orally, single dose
• DPH 50 mg
Participants received two DPH (Diphenhydramine hydrochloride) 25mg tablets orally, single dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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