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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01280591
First received: January 20, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pain, Postoperative
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
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Wake Time After Sleep Onset (WASO) Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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.

  • Sleep Efficiency Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subjects responded to the following question: Well Rested? not rested at all (1); somewhat unrested (2); completely rested (3)

  • Karolinska Sleep Diary - Sufficient Sleep [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subjects responded to Quality of sleep (10-point scale, where 1 was poor and 10 was excellent)

  • Subjective Sleep Questionnaire - Refreshing Nature of Your Sleep Last Night [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded

  • Cumulative Proportion of Subjects Taking Rescue Medication by Hour [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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).


Enrollment: 712
Study Start Date: October 2010
Study Completion Date: February 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111) 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
Experimental: Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111) Drug: 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
Active Comparator: Naproxen sodium 440 mg (BAYH6689) Drug: Naproxen sodium 440 mg (BAYH6689)
Participants received two Naproxen sodium 220 mg tablets orally, single dose
Active Comparator: DPH 50 mg Drug: DPH 50 mg
Participants received two DPH (Diphenhydramine hydrochloride) 25mg tablets orally, single dose

  Eligibility

Ages Eligible for Study:   12 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01280591

Locations
United States, Texas
Austin, Texas, United States, 78744
United States, Utah
Salt Lake City, Utah, United States, 84124
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01280591     History of Changes
Other Study ID Numbers: 14837
Study First Received: January 20, 2011
Results First Received: January 24, 2014
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Naproxen sodium
Diphenhydramine

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Naproxen
Diphenhydramine
Promethazine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Histamine H1 Antagonists

ClinicalTrials.gov processed this record on September 16, 2014