Evaluate Analgesic/Sedative Efficacy of Naproxen Sodium and Diphenhydramine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01118273
First received: April 15, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The objectives of the study are to evaluate the analgesic and hypnotic efficacy of naproxen sodium and diphenhydramine combination when compared to naproxen sodium, diphenhydramine, and an ibuprofen and diphenhydramine combination


Condition Intervention Phase
Sleep
Drug: Naproxen Sodium 440 mg (BAYH6689) / DPH 50mg
Drug: Naproxen Sodium 440 mg (BAYH6689)
Drug: Naproxen Sodium 220 mg (BAYH6689) / DPH 50mg
Drug: Naproxen Sodium 220 mg (BAYH6689)
Drug: DPH 50mg
Drug: Ibuprofen 400 mg / Diphenhydramine citrate 76 mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Pilot Study Assessing the Analgesic and Hypnotic Effect of Naproxen Sodium and Diphenhydramine Combination in Dental Pain

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Total Sleep Time Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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. In calculating the total sleep time, subjects who took rescue medication were treated as "awake" from the time the rescue medication was given until the end of the sleep period. In addition, if subjects rescued before sleep onset, their total sleep time was set to zero.


Secondary Outcome Measures:
  • Wake After Sleep Onset (WASO) Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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. WASO was defined as minutes of awake during the period of sleep onset and offset, where sleep onset is the first 20-minute block with 19 minutes of sleep.

  • Sleep Latency Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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 was defined as minutes to sleep onset since dosing, where sleep onset was the first 20-minute block with 19 minutes of sleep. For subjects who had not achieved sleep onset (e.g., due to taking rescue medication before achieving sleep onset), sleep latency was considered as censored at the time of wakening.

  • Global Assessment of Study Medication as a Sleep-aid [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 0 being poor to 4 being excellent: How would you rate the study medication you received as a sleep aid?

  • Karolinska Sleep Diary - Sleep Quality [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being very poor and 5 being very good: How was your sleep?

  • Karolinska Sleep Diary - Calmness of Sleep [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being very restless and 5 being very calm: How calm was your sleep?

  • Karolinska Sleep Diary - Easiness to Fall Asleep [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being very difficult to 5 being very easy: How easy was it to fall asleep?

  • Karolinska Sleep Diary - Premature Awakening [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being woke up much too early to 3 being no: Premature awakening?

  • Karolinska Sleep Diary - Ease of Awakening [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being very difficult to 5 being very easy: Ease of awakening?

  • Karolinska Sleep Diary - Well Rested [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being not rested at all to 3 being completely rested: Well-rested?

  • Karolinska Sleep Diary - Sufficient Sleep [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject rating of following question with 1 being no, definitely too little to 5 being yes, definitely enough: Did you get enough (sufficient) sleep?

  • Total Sleep Time by Subject Assessment [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject responded to: Please estimate the number of hours and minutes you think that you slept.

  • Sleep Quality Index [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Sleep Quality Index is the mean score of items, 'sleep quality', 'calm sleep', 'ease falling asleep', and 'slept throughout' on the Karolinska Sleep Diary, ranges from 1 (worst possible) to 5 (best possible).

  • Overall Rating of Severity in Categorical Pain Rating Scale Score [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject responded to question, 'My pain at this time is' by selecting one of the following choices: no pain (0), mild pain (1), moderate pain (2), or severe pain (3).

  • Change From Baseline in Categorical Pain Rating Scale Score [ Time Frame: Baseline and up to 10 hours ] [ Designated as safety issue: No ]
    Subjects responded to question, 'My pain at this time is' with following choices: no pain (0), mild pain (1), moderate pain (2), or severe pain (3). Subjects completed this question at baseline (post-dental surgery) and after sleep period. The following measure is the change in pain rating from baseline.

  • Overall Rating of Severity in Visual Analog Scale (VAS) Score [ Time Frame: At 10 hours ] [ Designated as safety issue: No ]
    Subjects marked a line on a 100-mm scale to indicate the severity of pain they are experiencing from 0 being no pain to 100 being worse possible pain.

  • Change From Baseline in Visual Analog Scale (VAS) Score [ Time Frame: Baseline and up to 10 hours ] [ Designated as safety issue: No ]
    Subjects completed the VAS scale at baseline (post-dental surgery) and after completion of the sleep period. Subjects marked a line on a 100-mm scale to indicate the severity of pain they are experiencing from 0 being no pain to 100 being worse possible pain.This measure indicates the change in pain severity rating on the VAS scale from baseline.

  • Overall Rating of Pain Relief [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subjects responded to question, "Overall, the relief from my starting pain was" by checking one of the following choices: 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 ]
    Subjects were allowed to "rescue" and take a non-study pain reliever if the pain was not tolerable. This measure represents for the time to taking rescue medication from the time the subject took study treatment.

  • Cumulative Proportion of Participants Taking Rescue Medication by Hour [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subjects were allowed to "rescue" and take a non-study pain reliever if the pain was not tolerable. This measure represents for the proportion of subjects who rescued in the study.

  • Global Assessment of Study Medication as a Pain Reliever [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subject responded to question, 'How would you rating this study medication you received as a pain-reliever?' with the following choices: Poor (0), Fair(1), Good(2), Very Good(3), Excellent(4)

  • Number of Times Participants Took Rescue Medication [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    Subjects were allowed to "rescue" and take a non-study pain reliever if the pain was not tolerable. This measure represents for the number of times rescue medication was taken by a subject.

  • Total Wake Time Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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.

  • Activity Mean Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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. Activity mean - average movement per minute.

  • Wake Episode Measured by Actigraphy [ Time Frame: Up to 10 hours ] [ Designated as safety issue: No ]
    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. Wake Episodes - # of blocks of continuous wake epochs (defined as 2 or more consecutive epochs scored as wake that ends when there is at least one epoch scored as sleep subsequent to the start of the wake epochs).


Enrollment: 162
Study Start Date: January 2008
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Naproxen Sodium 440 mg (BAYH6689) / DPH 50mg Drug: Naproxen Sodium 440 mg (BAYH6689) / DPH 50mg
Participants received 2 tablets of Naproxen Sodium 220 mg and 2 tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Active Comparator: Naproxen Sodium 440 mg (BAYH6689) Drug: Naproxen Sodium 440 mg (BAYH6689)
Participants received 2 tablets of Naproxen Sodium 220mg and 2 tablets of placebo, single dose, orally.
Experimental: Naproxen Sodium 220 mg (BAYH6689) / DPH 50mg Drug: Naproxen Sodium 220 mg (BAYH6689) / DPH 50mg
One dose of naproxen sodium 220 mg plus diphenhydramine 50 mg
Active Comparator: Naproxen Sodium 220 mg (BAYH6689) Drug: Naproxen Sodium 220 mg (BAYH6689)
Participants received 1 tablet of Naproxen Sodium 220 mg and 3 tablets of placebo, single dose, orally.
Active Comparator: DPH 50mg Drug: DPH 50mg
Participants received 2 tablets of Diphenhydramine hydrochloride (DPH) 25 mg and 2 tablets of placebo, single dose, orally.
Active Comparator: Ibuprofen 400 mg / Diphenhydramine citrate 76 mg Drug: Ibuprofen 400 mg / Diphenhydramine citrate 76 mg
Participants received 2 tablets of Advil PM (ibuprofen 200 mg and diphenhydramine citrate 38 mg) and 2 tablets of Placebo, single dose, orally.

  Eligibility

Ages Eligible for Study:   16 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy, ambulatory, male and female volunteers between 16-45 years of age;
  • Scheduled to undergo surgical removal of 1 to 3 impacted third molars, one of which must be at least a partial bony mandibular impaction;
  • 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 by 2030 h +/- 15 minutes 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 antiinflammatory drugs (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 negative 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;
  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: NCT01118273

Locations
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: NCT01118273     History of Changes
Other Study ID Numbers: 13053
Study First Received: April 15, 2010
Results First Received: January 24, 2014
Last Updated: May 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Bayer:
Naproxen sodium
Diphenhydramine
Drugs, Investigational

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

ClinicalTrials.gov processed this record on July 29, 2014