Clinical trial NCT01280591: Evaluate Analgesic/Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain, Postoperative
Keywords: Naproxen sodium
Diphenhydramine
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-01-21
Enrollment: 712
Sex: ALL
Minimum age (years): 12
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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 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

Primary outcomes:
measure: Wake Time After Sleep Onset (WASO) Measured by Actigraphy
timeFrame: Up to 10 hours
measure: Sleep Latency Measured by Actigraphy
timeFrame: Up to 10 hours
Secondary outcomes:
measure: Total Sleep Time Measured by Actigraphy
timeFrame: Up to 10 hours
measure: Sleep Efficiency Measured by Actigraphy
timeFrame: Up to 10 hours
measure: Global Assessment of Investigational Product as a Sleep Aid
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Sleep Quality
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Calmness of Sleep
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Easiness to Fall Asleep
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Premature Awakening
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Ease of Awakening
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Well Rested
timeFrame: Up to 10 hours
measure: Karolinska Sleep Diary - Sufficient Sleep
timeFrame: Up to 10 hours
measure: Subjective Sleep Questionnaire - Quality of Your Sleep Last Night
timeFrame: Up to 10 hours
measure: Subjective Sleep Questionnaire - Refreshing Nature of Your Sleep Last Night
timeFrame: Up to 10 hours
measure: Subjective Sleep Questionnaire - Time to Fall Asleep Last Night
timeFrame: Up to 10 hours
measure: 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
timeFrame: Up to 10 hours
measure: Change From Baseline in Pain Intensity
timeFrame: Baseline and up to 10 hours
measure: Overall Rating of Pain Relief
timeFrame: Up to 10 hours
measure: Time to Rescue Medication
timeFrame: Up to 10 hours
measure: Cumulative Proportion of Subjects Taking Rescue Medication by Hour
timeFrame: Up to 10 hours
measure: Global Assessment of Investigational Product as a Pain Reliever
timeFrame: Up to 10 hours
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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.