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CompletedNCT03404206Updated Jul 18, 2019Results posted

A Trial to Compare the Duration of Analgesic Efficacy and Safety of Naproxen Sodium Tablets and Ibuprofen Tablets in Postsurgical Dental Pain

A Phase 4 interventional study of Naproxen Sodium (Aleve, BAY117031) and Ibuprofen (Advil) in Pain, Postoperative, sponsored by Bayer. Completed at 1 site in United States. Open to participants aged 16 Years to 40 Years. Per ClinicalTrials.gov, last updated 2019-07-18.

Sponsored by Bayer · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
387
Allocation
Randomized
Ages
16 Years to 40 Years
Sex
All
01

Study summary

To compare the duration of analgesic efficacy as determined by the time to rescue medication of a single oral dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo over 24 hours in subjects experiencing moderate to severe post-impaction surgery dental pain.

To compare the overall analgesic effect (SPID 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo.

To compare the overall relief from pain (TOTPAR 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo.

02

Conditions studied

  • Pain, Postoperative

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Keywords

  • Postsurgical pain
03

Who can participate

Ages eligible
16 Years to 40 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Healthy, ambulatory, male or female volunteers 16-40 years of age;
  • Body mass index 18.0 to 30.0 kg/m\^2 inclusive;
  • Scheduled to undergo surgical removal of at least 2 mandibular partial or full bony impacted third molars. Up to two maxillary third molars may be removed regardless of impaction level. Supernumerary teeth present may also be removed at the discretion of the oral surgeon;
  • Mandibular molars must demonstrate modified Demirjian root classification stage D, E, F, G or H;

Exclusion criteria

Exclusion Criteria:

  • History of hypersensitivity to naproxen sodium, ibuprofen, nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational 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)
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
387 participants (actual)

Study arms

  • Experimental
    Naproxen Sodium (Aleve, BAY117031)

    Participants received one single dose of 440 mg naproxen sodium tablets (200 mg x 2 tablets, oral) after randomization

    Drug: Naproxen Sodium (Aleve, BAY117031)

  • Active comparator
    Ibuprofen (Advil)

    Participants received one single dose of 400 mg ibuprofen tablets (200 mg x 2 tablets, oral) after randomization

    Drug: Ibuprofen (Advil)

  • Placebo comparator
    Placebo

    Participants received one single dose of matching placebo tablets (2 tablets, oral) after randomization

    Drug: Placebo

Interventions

  • DrugNaproxen Sodium (Aleve, BAY117031)

    220 mg x 2 tablets, oral, single dose

  • DrugIbuprofen (Advil)

    200 mg x 2 tablets, oral, single dose

  • DrugPlacebo

    Matching placebo, 2 tablets, oral, single dose

05

What researchers measure

Primary outcomes

  1. Time to First Use of Rescue Medication

    Time to first use of rescue medication was estimated using Kaplan-Meier method. If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.

    Time frame: Up to 24 hours

Secondary outcomes

  1. Sum of Pain Intensity Difference (SPID)

    Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted sum of pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.

    Time frame: Up to 24 hours

  2. Total Pain Relief (TOTPAR)

    Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.

    Time frame: Up to 24 hours

06

Results

Posted Jul 18, 2019

Participant flow

The study was conducted at one center in the United States, between 12 February 2018 (first patient first visit) and 10 July 2018 (last patient last visit).

Participant flow — Overall Study
MilestoneNaproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)Placebo
Started16616655
Completed16216455
Not completed420
Withdrew: Withdrawal by subject110
Withdrew: Lost to follow-up310

Outcome measures

PrimaryTime to First Use of Rescue Medication

Time to first use of rescue medication was estimated using Kaplan-Meier method. If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.

Time frame:
Up to 24 hours
Reported as:
Number · hours
Time to First Use of Rescue Medication
hoursNaproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)Placebo
Minimum1.221.221.18
25th Percentile11.0178.2672.117
50th PercentileNA10.5332.533
75th PercentileNA14.11712.100
Maximum22.1718.2821.75
Statistical analysis
  • Naproxen Sodium (Aleve, BAY117031) vs Ibuprofen (Advil) · Log Rank · p = <0.001
  • Naproxen Sodium (Aleve, BAY117031) vs Placebo · Log Rank · p = <0.001
SecondarySum of Pain Intensity Difference (SPID)

Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted sum of pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.

Time frame:
Up to 24 hours
Reported as:
Mean · Scores on a scale * hours
Sum of Pain Intensity Difference (SPID)
Scores on a scale * hoursNaproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)Placebo
Sum of Pain Intensity Difference (SPID)83.29 ± 57.17748.54 ± 40.7059.96 ± 58.197
Statistical analysis
  • Naproxen Sodium (Aleve, BAY117031) vs Ibuprofen (Advil) · ANCOVA · Least squares means: -34.73 · 95% CI -45.67 to -23.8
  • Naproxen Sodium (Aleve, BAY117031) vs Placebo · ANCOVA · Least squares means: -73.43 · 95% CI -89.01 to -57.85
  • Ibuprofen (Advil) vs Placebo · ANCOVA · Least squares means: -38.7 · 95% CI -54.29 to -23.11
SecondaryTotal Pain Relief (TOTPAR)

Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.

Time frame:
Up to 24 hours
Reported as:
Mean · Scores on a scale * hours
Total Pain Relief (TOTPAR)
Scores on a scale * hoursNaproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)Placebo
Total Pain Relief (TOTPAR)47.16 ± 28.22828.96 ± 21.09713.40 ± 23.328
Statistical analysis
  • Naproxen Sodium (Aleve, BAY117031) vs Ibuprofen (Advil) · ANCOVA · Least squares means: -18.21 · 95% CI -23.52 to -12.89
  • Naproxen Sodium (Aleve, BAY117031) vs Placebo · ANCOVA · Least squares means: -33.72 · 95% CI -41.29 to -26.14
  • Ibuprofen (Advil) vs Placebo · ANCOVA · Least squares means: -15.51 · 95% CI -23.09 to -7.93

Adverse events

Collected over From start of study drug up to 10 days after the administration of study drug. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Naproxen Sodium (Aleve, BAY117031)0/166 (0%)1/166 (0.6%)25/166 (15.1%)
Placebo0/55 (0%)0/55 (0%)16/55 (29.1%)
Ibuprofen (Advil)0/166 (0%)0/166 (0%)31/166 (18.7%)
Most frequent serious events
Most frequent serious events
EventNaproxen Sodium (Aleve, BAY117031)PlaceboIbuprofen (Advil)
AppendicitisInfections and infestations1/1660/550/166
Most frequent other events
Showing 10 of 28
Most frequent other events
EventNaproxen Sodium (Aleve, BAY117031)PlaceboIbuprofen (Advil)
NauseaGastrointestinal disorders9/16611/5517/166
VomitingGastrointestinal disorders1/1667/557/166
HeadacheNervous system disorders3/1667/556/166
DizzinessNervous system disorders4/1661/555/166
Alveolar osteitisInfections and infestations4/1660/551/166
Abdominal pain upperGastrointestinal disorders0/1661/550/166
ConstipationGastrointestinal disorders0/1661/550/166
PyrexiaGeneral disorders0/1661/551/166
Pain in extremityMusculoskeletal and connective tissue disorders0/1661/550/166
Oropharyngeal painRespiratory, thoracic and mediastinal disorders2/1660/550/166

Baseline characteristics

Safety Population (included all subjects who were randomized and took at least one dose of investigational product)

Age, Continuous
Age, Continuous(years)Naproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)PlaceboTotal
Mean19.0 ± 2.9619.0 ± 2.6219.0 ± 2.9119.0 ± 2.80
Sex: Female, Male
Sex: Female, Male(Participants)Naproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)PlaceboTotal
Female778930196
Male897725191
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Naproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)PlaceboTotal
Hispanic or Latino23251058
Not Hispanic or Latino14314145329
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Naproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)PlaceboTotal
White14814848344
Black or African American2417
American Indian or Alaska Native3429
Asian1214
Native Hawaiian or Other Pacific Islander1315
Other115218
Pain Intensity Score
Pain Intensity Score(Participants)Naproxen Sodium (Aleve, BAY117031)Ibuprofen (Advil)PlaceboTotal
No Pain (0)0000
Mild Pain (1)0000
Moderate Pain (2)696723159
Severe Pain (3)979932228
07

Study locations

1 site
  • Jean Brown Research
    Salt Lake City, Utah 84124, United States
08

References and documents

Publications

  • Cooper SA, Desjardins P, Brain P, Paredes-Diaz A, Troullos E, Centofanti R, An B. Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial. Curr Med Res Opin. 2019 Dec;35(12):2149-2158. doi: 10.1080/03007995.2019.1655257. Epub 2019 Aug 27. PubMed 31402718 ↗

Study documents

  • Study protocol · Feb 15, 2018
  • Statistical analysis plan · Aug 24, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03404206
Lead sponsor
Bayer
Responsible party
Sponsor
First posted
Jan 19, 2018
Start date
Feb 12, 2018
Primary completion
Jul 6, 2018
Completion
Jul 10, 2018
Results posted
Jul 18, 2019
Last update
Jul 18, 2019

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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