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CompletedNCT04132336Updated Sep 1, 2021Results posted

Study to Find Out the Optimal Dose of Caffeine in the Combination Tablet of Naproxen Sodium and Caffeine in Patients Experiencing Moderate to Severe Pain After Having Wisdom Teeth Removed

A Phase 2 interventional study of Naproxen sodium/Caffeine (BAY2880376) and Naproxen sodium (Aleve) in Pain, Postoperative, sponsored by Bayer. Completed at 1 site in United States. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2021-09-01.

Sponsored by Bayer · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
193
Allocation
Randomized
Ages
16 Years and older
Sex
All
01

Study summary

The researchers in this study wanted to find out the optimal dose of Caffeine in the combination tablet of Naproxen Sodium and Caffeine that works in patients experiencing moderate to severe pain after having wisdom teeth removed. In the US, Naproxen has been marketed since 1976, and Naproxen Sodium has been approved for over-the-counter (OTC) use since 1994 for the temporary relief of minor aches and pains. Caffeine, which is generally consumed as coffee, tea or cocoa, has been shown to enhance the effectiveness of various pain relievers, and therefore is accepted as an additive to painkillers like aspirin and acetaminophen. Patients participating in this study underwent a surgery to remove 3 or 4 wisdom teeth. If the pain severity after the surgery met the study requirement, patients would receive oral tablet(s) of Naproxen Sodium and Caffeine, or Naproxen Sodium, or Caffeine, or placebo (drug with no active ingredient). Patients could also receive additional pain medication when needed. Researchers would also learn if the patients have any medical problems during the study.

02

Conditions studied

  • Pain, Postoperative

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Keywords

  • Dental pain
03

In context

Pain, Postoperative

5,093 studies on the registry are indexed under Pain, Postoperative; 1,140 are open to participants now.

This study's enrollment of 193 is above the median of 75 across 4,344 interventional studies indexed under Pain, Postoperative.

Browse Pain, Postoperative studies →

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Healthy, ambulatory, male or female volunteers 16 years of age or older;
  • Body mass index (BMI) 18.5 to 35.0 kg/m\^2 inclusive as measured by the National Institutes of Health (NIH) BMI Calculator;
  • Participants will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios: two full bony impactions; two partial bony impactions; one full bony impaction in combination with one partial bony impaction. supernumerary teeth present may also be removed at the discretion of the oral surgeon;
  • Have not taken any form of medication, nutritional supplements with analgesic properties (e.g. gamma-Aminobutyric acid [GABA], turmeric) or herbal supplements (i.e., St. John's Wort) within 5 days of admission (except for oral contraceptives, prophylactic antibiotics, multivitamin supplements, or other routine medications to treat benign conditions (such as antibiotics to treat acne), and agree not to take any medication (other than that provided to them) throughout the study;
  • Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator;
  • Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity Numerical Rating Scale (NRS) within 4.5 hours post-surgery.

Exclusion criteria

Exclusion Criteria:

  • History of hypersensitivity to naproxen sodium, caffeine, ibuprofen, nonsteroidal anti-inflammatory drug (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 (including hypertension and cardiac arrhythmia), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;
  • Participants with the following medical conditions may be eligible at the discretion of the investigator: attention deficit hyperactivity disorder (ADHD) on a stable dose regimen of methylphenidate/(dextro) amphetamine for at least 6 months; participants with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months;
  • Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months;
  • Relevant concomitant disease such as asthma (exercise induced asthma is permitted);
  • Current or past history of gastrointestinal ulceration, gastrointestinal bleeding or other bleeding disorder(s);
  • Acute illness or active local infection prior to surgery that can interfere with the conduct of the study in the judgment of the investigator;
  • Use of any over-the-counter (OTC) or prescription medications with which the administration of naproxen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated;
  • Use of any medications within 5 days of surgery until discharge from the study site (except oral contraceptives, prophylactic antibiotics, synthetic thyroid hormones, methylphenidate or medications to treat benign conditions such as antibiotics to treat acne);
  • Use of caffeine within 2 days prior to the study;
  • Habits of high consumption of caffeine (>400 mg/day equivalent to about 3-4 cups of coffee per day);
  • Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years);
  • Surgeon's trauma rating of severe following surgery.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
193 participants (actual)

Study arms

  • Experimental
    Naproxen sodium/caffeine - Dose 1

    Participants received a single dose of two tablets of naproxen sodium/caffeine (low dose/medium low dose) after extraction of third molars

    Drug: Naproxen sodium/Caffeine (BAY2880376)

  • Experimental
    Naproxen sodium/caffeine - Dose 2

    Participants received a single dose of two tablets of naproxen sodium/caffeine (low dose/low dose) after extraction of third molars

    Drug: Naproxen sodium/Caffeine (BAY2880376)

  • Experimental
    Naproxen sodium/caffeine - Dose 3

    Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ medium low dose) plus one tablet of placebo after extraction of third molars

    Drug: Naproxen sodium/Caffeine (BAY2880376)

  • Experimental
    Naproxen sodium/caffeine - Dose 4

    Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ low dose) plus one tablet of placebo after extraction of third molars

    Drug: Naproxen sodium/Caffeine (BAY2880376)

  • Active comparator
    Naproxen sodium

    Participants received a single dose of one tablet of naproxen sodium (low dose) plus one tablet of placebo after extraction of third molars

    Drug: Naproxen sodium (Aleve)

  • Active comparator
    Caffeine

    Participants received a single dose of two tablets of caffeine (medium low dose) after extraction of third molars

    Drug: Caffeine

  • Placebo comparator
    Placebo

    Participants received a single dose of two tablets of matching placebo after extraction of third molars

    Drug: Placebo

Interventions

  • DrugNaproxen sodium/Caffeine (BAY2880376)

    Tablet, oral, single dose

  • DrugNaproxen sodium (Aleve)

    Tablet, oral, single dose

  • DrugCaffeine

    Tablet, oral, single dose

  • DrugPlacebo

    Tablet, oral, single dose

06

What researchers measure

Primary outcomes

  1. Sum of Pain Intensity Difference (SPID) Over 8 Hours

    Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction.

    Time frame: Up to 8 hours post dose

Secondary outcomes

  1. Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose

    Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID 0-2 ranges from -20 to 20, SPID 0-4 ranges from -40 to 40 and SPID 0-12 ranges from -120 to 120. A higher value indicates a better pain reduction.

    Time frame: Up to 2 hours, 4 hours and 12 hours post dose

  2. Total Pain Relief (TOTPAR) Over 8 Hours

    Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 8 hours ranges from 0 to 32, a higher value indicates more pain relief.

    Time frame: Up to 8 hours post dose

  3. Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose

    Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR 0-2 ranges from 0 to 8, TOTPAR 0-4 ranges from 0 to 16, and TOTPAR 0-12 ranges from 0 to 48. A higher value indicates more pain relief

    Time frame: Up to 2 hours, 4 hours and 12 hours post dose

  4. Time to First Use of Rescue Medication

    Time frame: Up to 12 hours post dose

  5. The Cumulative Percentage of Participants Taking Rescue Medication

    Time frame: Up to 12 hours post dose

  6. Pain Intensity Difference (PID) at Each Evaluation

    Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement

    Time frame: Up to 12 hours post dose

  7. Peak Pain Intensity Difference (PID)

    Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). Participants circle a number (from 0 to 10) on the Numerical Rating Scale to indicate the severity the pain they are experiencing at baseline and at each post dose time point. For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score).

    Time frame: Up to 12 hours post dose

  8. Pain Relief Score at Each Evaluation

    Pain relief is 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)

    Time frame: Up to 12 hours post dose

  9. Peak Pain Relief Score

    Pain relief is 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). At each post-dose time point, participants check the appropriate box (from 0 to 4) on the Categorical Pain Relief Rating Scale to indicate the relief from starting pain at the post dose time points.

    Time frame: Up to 12 hours post dose

  10. Global Assessment of the Investigational Product

    Global assessment is performed either at 12 hours post-dose or immediately prior to the first intake of rescue medication. Global assessment is based on the question 'Overall, I would rate the study medication I received: 0=Poor, 1=Fair, 2=Good, 3=Very Good, 4=Excellent.'

    Time frame: Up to 12 hours post dose

  11. Number of Participants With Adverse Events

    Time frame: Up to 5 days post dose

  12. The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs

    Time frame: Up to 5 days post dose

07

Results

Posted Jun 16, 2021
Limitations and caveats
Other pre-specified outcomes (non-key secondary) "Time to first perceptible relief/meaningful relief/perceptible relief confirmed by meaningful relief" and "Cumulative percentage of subjects with at least '2-point PID' over time" were also analyzed

Participant flow

Study was conducted at a single center in United States with first participant first visit on 12-Nov-2019 and last participant last visit on 02-Mar-2020. Study was completed on 03-Mar-2020 (End of follow up, phone call).

Participant flow — Overall Study
MilestoneNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Started32323232321617
Completed32313232321617
Not completed0100000
Withdrew: Investigator decision0100000

Outcome measures

PrimarySum of Pain Intensity Difference (SPID) Over 8 Hours

Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction.

Time frame:
Up to 8 hours post dose
Reported as:
Mean · Scores on a scale*hours
Sum of Pain Intensity Difference (SPID) Over 8 Hours
Scores on a scale*hoursNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Sum of Pain Intensity Difference (SPID) Over 8 Hours35.45 ± 14.51737.87 ± 16.87630.70 ± 17.67936.02 ± 14.82529.95 ± 19.0678.75 ± 21.4656.03 ± 17.810
SecondarySum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose

Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID 0-2 ranges from -20 to 20, SPID 0-4 ranges from -40 to 40 and SPID 0-12 ranges from -120 to 120. A higher value indicates a better pain reduction.

Time frame:
Up to 2 hours, 4 hours and 12 hours post dose
Reported as:
Mean · Scores on a scale*hours
Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose
Scores on a scale*hoursNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
SPID 0-28.30 ± 3.1418.68 ± 3.7897.17 ± 3.7216.92 ± 3.5016.05 ± 3.5112.13 ± 4.0601.16 ± 2.925
SPID 0-418.02 ± 6.38719.26 ± 8.01915.58 ± 7.69717.05 ± 7.23214.33 ± 8.3914.50 ± 9.6042.59 ± 7.625
SPID 0-1250.58 ± 24.23752.45 ± 27.30544.80 ± 28.92952.45 ± 23.02243.08 ± 30.03412.44 ± 32.0591.15 ± 2.833
SecondaryTotal Pain Relief (TOTPAR) Over 8 Hours

Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 8 hours ranges from 0 to 32, a higher value indicates more pain relief.

Time frame:
Up to 8 hours post dose
Reported as:
Mean · Scores on a scale*hours
Total Pain Relief (TOTPAR) Over 8 Hours
Scores on a scale*hoursNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Total Pain Relief (TOTPAR) Over 8 Hours19.58 ± 7.00720.26 ± 7.67317.41 ± 8.06319.53 ± 6.44816.27 ± 8.5147.03 ± 9.2835.44 ± 7.709
SecondaryTotal Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose

Pain relief is 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 is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR 0-2 ranges from 0 to 8, TOTPAR 0-4 ranges from 0 to 16, and TOTPAR 0-12 ranges from 0 to 48. A higher value indicates more pain relief

Time frame:
Up to 2 hours, 4 hours and 12 hours post dose
Reported as:
Mean · Scores on a scale*hours
Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose
Scores on a scale*hoursNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
TOTPAR 0-24.83 ± 1.4014.77 ± 1.7314.22 ± 1.5963.97 ± 1.4363.52 ± 1.6441.66 ± 1.7671.06 ± 1.328
TOTPAR 0-410.27 ± 2.75010.29 ± 3.4498.84 ± 3.2869.28 ± 2.8427.86 ± 3.8133.59 ± 4.1482.44 ± 3.281
TOTPAR 0-1228.20 ± 12.26228.26 ± 12.69025.13 ± 13.29128.72 ± 10.67822.95 ± 13.20610.28 ± 13.8828.44 ± 12.419
SecondaryTime to First Use of Rescue Medication
Time frame:
Up to 12 hours post dose
Reported as:
Median · hours
Time to First Use of Rescue Medication
hoursNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Time to First Use of Rescue MedicationNA (NA to NA)NA (8.967 to NA)NA (8.817 to NA)NA (NA to NA)NA (8.125 to NA)2.083 (1.275 to NA)2.125 (1.408 to NA)
SecondaryThe Cumulative Percentage of Participants Taking Rescue Medication
Time frame:
Up to 12 hours post dose
Reported as:
Number · Percentage of participants
The Cumulative Percentage of Participants Taking Rescue Medication
Percentage of participantsNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
0.5 Hours Post-Dose0000000
1 Hour Post-Dose0000000
1.5 Hours Post-Dose03.23.10037.525.0
2 Hours Post-Dose03.23.1005037.5
3 Hours Post-Dose06.56.33.115.656.356.3
4 Hours Post-Dose3.16.59.43.118.856.368.8
5 Hours Post-Dose9.46.515.63.118.862.568.8
6 Hours Post-Dose9.49.718.86.321.968.868.8
7 Hours Post-Dose12.59.721.96.321.968.868.8
8 Hours Post-Dose15.69.721.99.421.968.875.0
9 Hours Post-Dose21.925.825.09.428.168.875.0
10 Hours Post-Dose25.025.828.115.631.368.875.0
11 Hours Post-Dose25.025.828.115.634.468.875.0
12 Hours Post-Dose25.029.028.118.834.475.075.0
SecondaryPain Intensity Difference (PID) at Each Evaluation

Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement

Time frame:
Up to 12 hours post dose
Reported as:
Mean · Scores on a scale
Pain Intensity Difference (PID) at Each Evaluation
Scores on a scaleNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
0.5 Hours Post-Dose2.3 ± 2.072.6 ± 1.822.1 ± 2.231.4 ± 1.561.5 ± 1.340.8 ± 0.980.5 ± 0.89
1 Hour Post-Dose4.2 ± 1.884.2 ± 2.443.7 ± 1.953.4 ± 2.392.9 ± 1.881.2 ± 2.260.6 ± 1.71
1.5 Hours Post-Dose4.9 ± 1.675.1 ± 2.264.3 ± 1.984.2 ± 2.323.7 ± 2.161.2 ± 2.790.7 ± 1.74
2 Hours Post-Dose5.1 ± 1.765.5 ± 2.204.3 ± 2.234.8 ± 2.234.1 ± 2.221.1 ± 2.670.5 ± 1
3 Hours Post-Dose5.0 ± 1.825.4 ± 2.274.3 ± 2.335.0 ± 2.294.0 ± 2.831.1 ± 2.850.6 ± 2.42
4 Hours Post-Dose4.8 ± 2.175.2 ± 2.594.1 ± 2.625.1 ± 2.274.3 ± 2.821.3 ± 3.110.9 ± 2.78
5 Hours Post-Dose4.7 ± 2.285.0 ± 2.424.0 ± 2.725.0 ± 2.254.1 ± 2.831.1 ± 3.141.0 ± 2.92
6 Hours Post-Dose4.6 ± 2.244.8 ± 2.423.8 ± 2.874.9 ± 2.403.9 ± 2.881.1 ± 3.191.0 ± 3.06
7 Hours Post-Dose4.3 ± 2.554.5 ± 2.453.8 ± 3.074.7 ± 2.313.9 ± 3.081.1 ± 3.360.8 ± 2.49
8 Hours Post-Dose4.0 ± 2.534.2 ± 2.653.7 ± 3.124.3 ± 2.293.7 ± 2.960.9 ± 2.950.7 ± 2.65
9 Hours Post-Dose3.8 ± 2.713.8 ± 3.123.6 ± 3.004.2 ± 2.453.6 ± 3.141.1 ± 3.090.8 ± 2.74
10 Hours Post-Dose3.8 ± 2.883.7 ± 3.043.4 ± 3.154.1 ± 2.603.3 ± 3.071.1 ± 3.070.9 ± 2.99
11 Hours Post-Dose3.8 ± 2.923.5 ± 3.023.6 ± 3.174.2 ± 2.793.1 ± 3.020.8 ± 2.990.9 ± 2.96
12 Hours Post-Dose3.8 ± 2.973.6 ± 3.063.5 ± 3.384.0 ± 2.923.1 ± 2.970.8 ± 3.000.9 ± 2.96
SecondaryPeak Pain Intensity Difference (PID)

Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). Participants circle a number (from 0 to 10) on the Numerical Rating Scale to indicate the severity the pain they are experiencing at baseline and at each post dose time point. For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score).

Time frame:
Up to 12 hours post dose
Reported as:
Mean · Scores on a scale
Peak Pain Intensity Difference (PID)
Scores on a scaleNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Peak Pain Intensity Difference (PID)6.0 ± 1.536.2 ± 1.975.9 ± 2.016.3 ± 1.725.3 ± 2.572.7 ± 2.942.3 ± 2.98
SecondaryPain Relief Score at Each Evaluation

Pain relief is 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)

Time frame:
Up to 12 hours post dose
Reported as:
Mean · Scores on a scale
Pain Relief Score at Each Evaluation
Scores on a scaleNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
0.5 Hours Post-Dose1.6 ± 1.081.5 ± 0.891.5 ± 1.020.9 ± 0.801.0 ± 0.740.6 ± 0.620.4 ± 0.63
1 Hours Post-Dose2.4 ± 0.842.3 ± 1.222.2 ± 0.912.0 ± 1.141.8 ± 0.910.9 ± 1.000.6 ± 0.81
1.5 Hours Post-Dose2.8 ± 0.642.8 ± 0.992.3 ± 0.872.4 ± 0.912.0 ± 1.050.9 ± 1.240.6 ± 0.73
2 Hours Post-Dose2.8 ± 0.852.9 ± 1.012.4 ± 1.012.6 ± 0.792.2 ± 1.010.8 ± 1.050.5 ± 0.82
3 Hours Post-Dose2.8 ± 0.792.8 ± 0.972.4 ± 1.042.6 ± 0.912.1 ± 1.210.9 ± 1.240.6 ± 1.09
4 Hours Post-Dose2.7 ± 1.072.7 ± 1.192.3 ± 1.162.7 ± 0.962.2 ± 1.261.0 ± 1.370.8 ± 1.18
5 Hours Post-Dose2.6 ± 1.162.6 ± 1.152.3 ± 1.272.7 ± 1.002.2 ± 1.240.9 ± 1.360.8 ± 1.18
6 Hours Post-Dose2.4 ± 1.162.6 ± 1.182.2 ± 1.352.7 ± 1.102.1 ± 1.300.9 ± 1.450.8 ± 1.24
7 Hours Post-Dose2.3 ± 1.342.5 ± 1.152.1 ± 1.382.5 ± 1.082.1 ± 1.290.9 ± 1.500.8 ± 1.28
8 Hours Post-Dose2.1 ± 1.332.3 ± 1.282.1 ± 1.462.4 ± 1.192.0 ± 1.280.8 ± 1.330.7 ± 1.25
9 Hours Post-Dose2.2 ± 1.402.1 ± 1.482.0 ± 1.452.3 ± 1.121.9 ± 1.410.9 ± 1.360.8 ± 1.34
10 Hours Post-Dose2.2 ± 1.512.0 ± 1.431.8 ± 1.422.3 ± 1.281.8 ± 1.410.9 ± 1.360.8 ± 1.34
11 Hours Post-Dose2.1 ± 1.521.9 ± 1.401.9 ± 1.482.4 ± 1.341.4 ± 1.320.8 ± 1.340.8 ± 1.34
12 Hours Post-Dose2.2 ± 1.551.9 ± 1.462.0 ± 1.512.2 ± 1.451.6 ± 1.390.8 ± 1.340.8 ± 1.34
SecondaryPeak Pain Relief Score

Pain relief is 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). At each post-dose time point, participants check the appropriate box (from 0 to 4) on the Categorical Pain Relief Rating Scale to indicate the relief from starting pain at the post dose time points.

Time frame:
Up to 12 hours post dose
Reported as:
Mean · Scores on a scale
Peak Pain Relief Score
Scores on a scaleNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Peak Pain Relief Score3.3 ± 0.623.2 ± 0.783.0 ± 0.823.1 ± 0.662.6 ± 1.011.6 ± 1.551.3 ± 1.39
SecondaryGlobal Assessment of the Investigational Product

Global assessment is performed either at 12 hours post-dose or immediately prior to the first intake of rescue medication. Global assessment is based on the question 'Overall, I would rate the study medication I received: 0=Poor, 1=Fair, 2=Good, 3=Very Good, 4=Excellent.'

Time frame:
Up to 12 hours post dose
Reported as:
Count of participants · Participants
Global Assessment of the Investigational Product
ParticipantsNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Poor (0)11114810
Fair (1)2142512
Good (2)5697641
Very Good (3)181413171423
Excellent (4)6955310
SecondaryNumber of Participants With Adverse Events
Time frame:
Up to 5 days post dose
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
Number of Participants With Adverse Events6312354
SecondaryThe Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs
Time frame:
Up to 5 days post dose
Reported as:
Count of participants · Participants
The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs
ParticipantsNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs0000000

Adverse events

Collected over Up to 5 days post-dose. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Naproxen Sodium/Caffeine-Dose 10/32 (0%)0/32 (0%)6/32 (18.8%)
Naproxen Sodium/Caffeine-Dose 20/32 (0%)0/32 (0%)3/32 (9.4%)
Naproxen Sodium/Caffeine-Dose 30/32 (0%)0/32 (0%)1/32 (3.1%)
Naproxen Sodium/Caffeine-Dose 40/32 (0%)0/32 (0%)2/32 (6.3%)
Naproxen Sodium0/32 (0%)0/32 (0%)3/32 (9.4%)
Caffeine0/16 (0%)0/16 (0%)5/16 (31.3%)
Placebo0/17 (0%)0/17 (0%)4/17 (23.5%)
Most frequent other events
Showing 10 of 16
Most frequent other events
EventNaproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlacebo
NauseaGastrointestinal disorders1/321/320/322/322/324/160/17
HeadacheNervous system disorders0/320/320/320/320/322/160/17
VomitingGastrointestinal disorders2/320/320/320/320/321/162/17
Ear painEar and labyrinth disorders0/320/320/320/320/321/160/17
EpistaxisRespiratory, thoracic and mediastinal disorders2/320/321/320/320/320/160/17
Cold sweatSkin and subcutaneous tissue disorders0/320/320/320/320/321/160/17
Chest discomfortGeneral disorders0/320/320/320/320/320/161/17
DizzinessNervous system disorders1/321/320/321/320/320/161/17
Paranasal sinus discomfortRespiratory, thoracic and mediastinal disorders0/320/320/320/320/320/161/17
TachycardiaCardiac disorders0/320/320/320/321/320/160/17

Baseline characteristics

Age, Continuous
Age, Continuous(years)Naproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlaceboTotal
Mean17.0 ± 1.0317.4 ± 2.4217.1 ± 1.3417.3 ± 1.4917.9 ± 2.7417.3 ± 1.7017.7 ± 1.4017.4 ± 1.86
Sex: Female, Male
Sex: Female, Male(Participants)Naproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlaceboTotal
Female13141610145577
Male19181622181112116
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Naproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlaceboTotal
Hispanic or Latino200323010
Not Hispanic or Latino30323229301317183
Unknown or Not Reported00000000
Baseline Pain Intensity Score
Baseline Pain Intensity Score(Participants)Naproxen Sodium/Caffeine-Dose 1Naproxen Sodium/Caffeine-Dose 2Naproxen Sodium/Caffeine-Dose 3Naproxen Sodium/Caffeine-Dose 4Naproxen SodiumCaffeinePlaceboTotal
No Pain (0)00000000
Mild Pain (1)00000000
Moderate Pain (2)15131211113570
Severe Pain (3)17192021211312123
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Study locations

1 site
  • JBR Clinical Research
    Salt Lake City, Utah 84107, United States
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References and documents

Study documents

  • Study protocol · Aug 22, 2019
  • Statistical analysis plan · May 13, 2020

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

Individual participant data

Plan to share: Undecided — Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 1, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04132336
Lead sponsor
Bayer
Responsible party
Sponsor
First posted
Oct 18, 2019
Start date
Nov 12, 2019
Primary completion
Mar 2, 2020
Completion
Mar 3, 2020
Results posted
Jun 16, 2021
Last update
Sep 1, 2021

Oversight

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

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