Back to resultsEvaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain (Morpheus/DPH)
Primary Purpose
Pain, Postoperative
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111)
Naproxen Sodium 440 mg (BAYH6689)
DPH 50 mg
Sponsored by
About this trial
This is an interventional treatment trial for Pain, Postoperative focused on measuring Naproxen sodium, Diphenhydramine
Eligibility Criteria
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 non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy.
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111)
Naproxen Sodium 440 mg (BAYH6689)
DPH 50 mg
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Total Sleep Time Measured by Actigraphy
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.
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.
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).
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)
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)
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)
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)
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)
Karolinska Sleep Diary - Well Rested
Subjects responded to the following question: Well Rested? not rested at all (1); somewhat unrested (2); completely rested (3)
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)
Subjective Sleep Questionnaire - Quality of Your Sleep Last Night
Subject evaluated sleep quality on a 10-point scale, where 1 was poor and 10 was excellent.
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)
Subjective Sleep Questionnaire - Time to Fall Asleep Last Night
Subjects responded to Estimate of how long it took to fall asleep (minutes)
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)
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
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).
Time to Rescue Medication
If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded
Cumulative Proportion of Participants Taking Rescue Medication by Hour
If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01495858
Brief Title
Evaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain
Acronym
Morpheus/DPH
Official Title
A Multicenter, Randomized, Double-Blind, Parallel Group Trial Assessing the Efficacy and Safety of Naproxen Sodium and Diphenhydramine Combination in Postsurgical Dental Pain With Phase Advanced Sleep
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of the study is to evaluate the efficacy and safety of a single oral dose of naproxen sodium 440 mg in combination with DPH (diphenhydramine) 25 mg in subjects with postsurgical dental pain and phase advanced sleep.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative
Keywords
Naproxen sodium, Diphenhydramine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
267 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111)
Arm Type
Experimental
Arm Title
Naproxen Sodium 440 mg (BAYH6689)
Arm Type
Active Comparator
Arm Title
DPH 50 mg
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111)
Intervention Description
Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.
Intervention Type
Drug
Intervention Name(s)
Naproxen Sodium 440 mg (BAYH6689)
Intervention Description
Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.
Intervention Type
Drug
Intervention Name(s)
DPH 50 mg
Intervention Description
Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Primary Outcome Measure Information:
Title
Wake Time After Sleep Onset (WASO) Measured by Actigraphy
Description
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.
Time Frame
Up to 10 hours
Title
Sleep Latency Measured by Actigraphy
Description
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.
Time Frame
Up to 10 hours
Secondary Outcome Measure Information:
Title
Total Sleep Time Measured by Actigraphy
Description
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.
Time Frame
Up to 10 hours
Title
Sleep Efficiency Measured by Actigraphy
Description
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.
Time Frame
Up to 10 hours
Title
Global Assessment of Investigational Product as a Sleep Aid
Description
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).
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Sleep Quality
Description
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)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Calmness of Sleep
Description
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)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Easiness to Fall Asleep
Description
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)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Premature Awakening
Description
Subjects responded to the following question : Premature awakening? woke up much too early (1); woke up somewhat too early (2); no (3)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Ease of Awakening
Description
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)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Well Rested
Description
Subjects responded to the following question: Well Rested? not rested at all (1); somewhat unrested (2); completely rested (3)
Time Frame
Up to 10 hours
Title
Karolinska Sleep Diary - Sufficient Sleep
Description
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)
Time Frame
Up to 10 hours
Title
Subjective Sleep Questionnaire - Quality of Your Sleep Last Night
Description
Subject evaluated sleep quality on a 10-point scale, where 1 was poor and 10 was excellent.
Time Frame
Up to 10 hours
Title
Subjective Sleep Questionnaire - Refreshing Nature of Your Sleep Last Night
Description
Subjects responded to Refreshing nature of sleep (10-point scale, where 1 was not refreshing and 10 was very refreshing)
Time Frame
Up to 10 hours
Title
Subjective Sleep Questionnaire - Time to Fall Asleep Last Night
Description
Subjects responded to Estimate of how long it took to fall asleep (minutes)
Time Frame
Up to 10 hours
Title
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
Description
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)
Time Frame
Up to 10 hours
Title
Change From Baseline in Pain Intensity
Description
Pain Severity was collected on a 4-point categorical scale: 0=no pain, 1=mild pain, 2=moderate pain, 4=severe pain
Time Frame
Baseline and up to 10 hours
Title
Overall Rating of Pain Relief
Description
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).
Time Frame
Up to 10 hours
Title
Time to Rescue Medication
Description
If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded
Time Frame
Up to 10 hours
Title
Cumulative Proportion of Participants Taking Rescue Medication by Hour
Description
If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded
Time Frame
Up to 10 hours
Title
Global Assessment of Investigational Product as a Pain Reliever
Description
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).
Time Frame
Up to 10 hours
Other Pre-specified Outcome Measures:
Title
Vital Signs: Mean Change From Baseline in Systolic Blood Pressure at Day 2
Time Frame
Baseline and day 2
Title
Vital Signs: Mean Change From Baseline in Diastolic Blood Pressure at Day 2
Time Frame
Baseline and Day 2
Title
Vital Signs: Mean Change From Baseline in Pulse Rate at Day 2
Time Frame
Baseline and day 2
Title
Vital Signs: Mean Change From Baseline in Respiratory Rate at Day 2
Time Frame
Baseline and day 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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 non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25996289
Citation
Cooper S, Laurora I, Wang Y, Venkataraman P, An R, Roth T. Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia. Int J Clin Pract. 2015 Oct;69(10):1149-58. doi: 10.1111/ijcp.12669. Epub 2015 May 21.
Results Reference
derived
Learn more about this trial
Evaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain
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