A Phase 3 interventional study of Naproxen sodium and caffeine (BAY2880376) and Naproxen sodium (Aleve) in Postoperative Dental Pain, sponsored by Bayer. Completed at 1 site in United States. Open to participants aged 16 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-25.
Sponsored by Bayer · Phase 3, Interventional, and Treatment
Researchers are looking for a better way to relieve pain in people, such as after dental surgery.
Participants in this study, have had 3 or 4 third molars (cheek teeth) removed and subsequently have moderate to severe tooth pain.
The study treatment naproxen sodium suppresses inflammatory pain by reducing inflammation.
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 effect of various painkillers, and therefore is accepted as an additive.
The main purpose of this study is to learn how well a fixed-dose combination of naproxen sodium and caffeine relieves pain compared to each single ingredient as well as to placebo in participants after molar removal.
A placebo is a treatment that looks like a medicine but does not have any medicine in it.
To answer this, the researchers will compare the amount of pain decrease over 8 hours in participants who received a single dose of either:
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This study's enrollment of 541 is above the median of 100 across 121 interventional studies indexed under Toothache.
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Exclusion Criteria:
Participants will receive a single dose of one tablet of naproxen sodium/caffeine plus one tablet of placebo after extraction of third molars.
Drug: Naproxen sodium and caffeine (BAY2880376)
Participants will receive a single dose of two tablets of naproxen sodium/caffeine after extraction of third molars.
Drug: Naproxen sodium and caffeine (BAY2880376)
Participants will receive a single dose of one tablet of naproxen sodium plus one tablet of placebo after extraction of third molars.
Drug: Naproxen sodium (Aleve)
Participants will receive a single dose of two tablets of caffeine after extraction of third molars.
Drug: Caffeine
Participants will receive a single dose of two tablets of matching placebo after extraction of third molars.
Drug: Placebo
Tablet, oral use, single dose
Tablet, oral use, single dose
Tablet, oral use, single dose
Tablet, oral use, single dose
Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose
Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be 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 the values over the relevant time period. For SPID (0-8), eight PIDs are summed up, which is minimally 0, if there is no pain relief or maximally 80, if there is very strong pain and significant pain relief.
Time frame: Up to 8 hours post-dose
Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose
Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be 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 the values over the relevant time period. For SPID(0-i), i PIDs are summed up, which minimally is 0, if there is no pain relief or maximally i\*10, if there is very strong pain and significant pain relief.
Time frame: from 0 to 2, 4, 6, 12 and 24 hours post-dose
Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose
Total Pain Relief (TOTPAR) is a cumulative measure that evaluates the overall pain relief over a specific time frame from 0-2,0-4,0-6,0-8,0-12 and 0-24 following drug administration. It is calculated by multiplying the pain relief score from the categorical pain relief scale at each time post-dose time by multiplying the duration (in hours) since the preceding time point and then adding these values. Categorical Pain Relief Scale measure the degree of pain relief using a scale from 0 to 4, in which 0 is no relief, 1 a little relief, 2 some relief, 3 a lot of relief and 4 complete relief. Higher values of TOTPAR indicates better pain relief and suggest that the investigational product provided consistence and meaningful pain relief over the period. Low TOTPAR values indicates minimal pain relief or short-lasting efficacy.
Time frame: up to 24 hours post-dose
Time to First Use of Rescue Medication
Time frame: Up to 24 hours post-dose
The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period
Time frame: Up to 24 hours post-dose
Time to First Perceptible Relief Measured by a Stopwatch
Time frame: Up to 24 hours post-dose
Time to Meaningful Relief Measured by a Stopwatch
meaningful relief is the point when the participant perceives their pain as significant and meaningful to them using the double-stopwatched method that allows to differentiate between the onset of the analgesic effect (first perceptible pain relief) and the onset of meaningful pain relief
Time frame: Up to 24 hours post-dose
Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief
Time frame: Up to 24 hours post-dose
Pain Intensity Difference (PID)
Pain Intensity Difference (PID) is the change of pain intensity at a specific time point compared to baseline using the Numerical Rating Scale from 0 to 10. Value of 0 score means no pain and 10 score result means the worst possible pain. For each post-dose time point, pain intensity differences will be derived by subtracting the pain intensity at the post-dose time point from the baseline intensity score. Positive PID values indicate pain relief (reduction in pain intensity), while negative or small PID values suggest little or no reduction in pain intensity
Time frame: up to 24 hours post-dose
Pain Relief Score
Pain Relief Score (PRS): 0 = No Relief; 1 = A Little Relief; 2 = Some Relief; 3 = A Lot of Relief; 4 = Complete Relief.
Time frame: Up to 24 hours post-dose
Peak Pain Intensity Difference (PID)
The Peak Pain Intensity (peak PID) refers to the maximum change in pain intensity from baseline observed at any post-dose time point using the Numerical Rating Scale from 0 to 10. Value of 0 score means no pain and 10 score result means the worst possible pain. Participants record their pain intensity assessment in the time frame points and the highest value is identified as the Peak Pain Intensity. A high peak pain intensuty (higher value on NRS) indicates severe pain and a less effective analgesic response, and a lower value signifies better pain control and a more effective response.
Time frame: Up to 24 hours post-dose
Number of Participants With Certain Peak Pain Relief Score
Number of participants with pain relief score 4, 3, 2, 1. The Peak Pain Relief Score refers to the highest level of pain relief a participant reported at any time point during the study period. It provides an overview of the maximum effectiveness of the treatment at any given point during the observation period using the Categorical Pain Relief Scale which measure the degree of pain relief using a scale from 0 to 4, in which 0 is no relief, 1 a little relief, 2 some relief, 3 a lot of relief and 4 complete relief. A high socre closer indicates significant pain relief and reflects the effectiveness of the analgesic treatment. A score closer to 0 indicates little to no pain relief and suggests limited treatment efficacy.
Time frame: Up to 24 hours post-dose
Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time
Time frame: Up to 24 hours post-dose
Global Assessment of Pain Relief of the Investigational Product
Number of participants with overall rating poor, fair, good, very good, excellent 24 hour post-dose
Time frame: 24 hours post-dose
Number of Participants With Adverse Events
Number of participants with at least one treatment emergent adverse event
Time frame: Up to 5 days post-dose
Number of Participants With Significant Changes in Vital Signs Since Baseline
Time frame: Up to 5 days post-dose
The clinical study was conducted at a single study site in the United States between 21 September 2022 (first participant first visit) and 29 January 2024 (last participant last visit).
| Milestone | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Started | 147 | 148 | 147 | 50 | 49 |
| Completed | 145 | 144 | 142 | 49 | 47 |
| Not completed | 2 | 4 | 5 | 1 | 2 |
| Withdrew: Withdrawal by subject | 1 | 2 | 2 | 0 | 2 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 1 | 3 | 1 | 0 |
Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be 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 the values over the relevant time period. For SPID (0-8), eight PIDs are summed up, which is minimally 0, if there is no pain relief or maximally 80, if there is very strong pain and significant pain relief.
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 31.293 ± 1.441 | 37.242 ± 1.436 | 31.082 ± 1.443 | 5.146 ± 2.470 | 8.622 ± 2.521 |
Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be 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 the values over the relevant time period. For SPID(0-i), i PIDs are summed up, which minimally is 0, if there is no pain relief or maximally i\*10, if there is very strong pain and significant pain relief.
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| 0-2 hours post-dose | 7.347 ± 0.341 | 8.950 ± 0.340 | 7.973 ± 0.341 | 1.876 ± 0.585 | 1.567 ± 0.597 |
| 0-4 hours post-dose | 15.899 ± 0.688 | 19.210 ± 0.686 | 16.627 ± 0.689 | 2.924 ± 1.179 | 3.982 ± 1.204 |
| 0-6 hours post-dose | 23.851 ± 1.057 | 28.632 ± 1.053 | 24.381 ± 1.058 | 4.024 ± 1.812 | 6.308 ± 1.849 |
| 0-12 hours post-dose | 44.207 ± 2.266 | 51.737 ± 2.258 | 42.907 ± 2.268 | 7.003 ± 3.883 | 13.455 ± 3.964 |
| 0-24 hours post-dose | 77.596 ± 4.949 | 83.884 ± 4.930 | 72.796 ± 4.953 | 12.533 ± 8.481 | 28.400 ± 8.656 |
Total Pain Relief (TOTPAR) is a cumulative measure that evaluates the overall pain relief over a specific time frame from 0-2,0-4,0-6,0-8,0-12 and 0-24 following drug administration. It is calculated by multiplying the pain relief score from the categorical pain relief scale at each time post-dose time by multiplying the duration (in hours) since the preceding time point and then adding these values. Categorical Pain Relief Scale measure the degree of pain relief using a scale from 0 to 4, in which 0 is no relief, 1 a little relief, 2 some relief, 3 a lot of relief and 4 complete relief. Higher values of TOTPAR indicates better pain relief and suggest that the investigational product provided consistence and meaningful pain relief over the period. Low TOTPAR values indicates minimal pain relief or short-lasting efficacy.
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| 0-2 hours post-dose | 3.284 ± 0.114 | 3.870 ± 0.114 | 3.417 ± 0.115 | 1.047 ± 0.196 | 1.216 ± 0.200 |
| 0-4 hours post-dose | 7.781 ± 0.287 | 9.118 ± 0.286 | 8.102 ± 0.287 | 2.120 ± 0.492 | 3.168 ± 0.502 |
| 0-6 hours post-dose | 12.098 ± 0.465 | 14.061 ± 0.464 | 12.420 ± 0.466 | 3.228 ± 0.798 | 4.870 ± 0.814 |
| 0-8 hours post-dose | 16.227 ± 0.645 | 18.625 ± 0.642 | 16.225 ± 0.645 | 4.327 ± 1.105 | 6.552 ± 1.128 |
| 0-12 hours post-dose | 23.512 ± 1.029 | 26.461 ± 1.026 | 22.767 ± 1.030 | 6.264 ± 1.764 | 9.700 ± 1.801 |
| 0-24 hours post-dose | 41.596 ± 2.281 | 43.908 ± 2.272 | 39.127 ± 2.283 | 12.047 ± 3.909 | 18.975 ± 3.990 |
| Hours | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Time to First Use of Rescue Medication | NA (17.33 to NA) | NA (14.08 to NA) | 19.72 (11.08 to NA) | 2.07 (1.72 to 2.75) | 2.65 (1.67 to 7.28) |
| proportion | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| 0.5 hour | 0 | 0 | 0 | 0 | 0 |
| less or equal 1 hour | 0.007 | 0 | 0.007 | 0.04 | 0.02 |
| less or equal 1.5 hour | 0.027 | 0.007 | 0.007 | 0.3 | 0.2 |
| less or equal 2 hours | 0.1 | 0.034 | 0.048 | 0.4 | 0.5 |
| less or equal 3 hours | 0.1 | 0.1 | 0.1 | 0.7 | 0.5 |
| less or equal 4hours | 0.2 | 0.1 | 0.1 | 0.7 | 0.6 |
| less or equal 5 hours | 0.2 | 0.1 | 0.1 | 0.7 | 0.6 |
| less or equal 6 hours | 0.2 | 0.1 | 0.2 | 0.8 | 0.6 |
| less or equal 7 hours | 0.2 | 0.1 | 0.2 | 0.8 | 0.6 |
| less or equal 8 hours | 0.2 | 0.1 | 0.3 | 0.8 | 0.6 |
| less or equal 9 hours | 0.3 | 0.2 | 0.3 | 0.8 | 0.7 |
| less or equal 10 hours | 0.3 | 0.2 | 0.4 | 0.8 | 0.7 |
| less or equal 11 hours | 0.4 | 0.3 | 0.4 | 0.8 | 0.7 |
| less or equal 12 hours | 0.4 | 0.3 | 0.4 | 0.8 | 0.7 |
| less or equal 14 hours | 0.4 | 0.4 | 0.4 | 0.8 | 0.7 |
| less or equal 16 hours | 0.4 | 0.4 | 0.5 | 0.8 | 0.7 |
| less or equal 18 hours | 0.4 | 0.4 | 0.5 | 0.8 | 0.7 |
| less or equal 20 hours | 0.4 | 0.4 | 0.5 | 0.8 | 0.7 |
| less or equal 22 hours | 0.4 | 0.4 | 0.5 | 0.8 | 0.7 |
| less or equal 24 hours | 0.4 | 0.4 | 0.5 | 0.8 | 0.7 |
| Hours | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Time to First Perceptible Relief Measured by a Stopwatch | 0.39 (0.33 to 0.42) | 0.35 (0.32 to 0.41) | 0.35 (0.32 to 0.39) | 0.60 (0.42 to 4.13) | 1.93 (0.51 to NA) |
meaningful relief is the point when the participant perceives their pain as significant and meaningful to them using the double-stopwatched method that allows to differentiate between the onset of the analgesic effect (first perceptible pain relief) and the onset of meaningful pain relief
| Hours | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Time to Meaningful Relief Measured by a Stopwatch | 0.83 (0.71 to 0.92) | 0.76 (0.67 to 0.85) | 0.79 (0.67 to 0.93) | NA (2.24 to NA) | 5.63 (2.11 to 5.78) |
| Hours | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | 0.83 (0.71 to 0.92) | 0.76 (0.67 to 0.85) | 0.79 (0.67 to 0.93) | NA (2.24 to NA) | 5.63 (2.11 to 5.78) |
Pain Intensity Difference (PID) is the change of pain intensity at a specific time point compared to baseline using the Numerical Rating Scale from 0 to 10. Value of 0 score means no pain and 10 score result means the worst possible pain. For each post-dose time point, pain intensity differences will be derived by subtracting the pain intensity at the post-dose time point from the baseline intensity score. Positive PID values indicate pain relief (reduction in pain intensity), while negative or small PID values suggest little or no reduction in pain intensity
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Baseline | 7.6 ± 1.22 | 7.6 ± 1.20 | 7.8 ± 1.21 | 7.7 ± 1.39 | 7.7 ± 0.99 |
| 0.5 hours post-dose | 1.8 ± 1.89 | 2.3 ± 1.91 | 2.4 ± 1.98 | 1.0 ± 1.38 | 0.6 ± 1.18 |
| 1 hour post-dose | 3.4 ± 2.40 | 4.3 ± 2.18 | 3.7 ± 2.23 | 0.8 ± 1.67 | 0.7 ± 1.89 |
| 1.5 hours post-dose | 4.0 ± 2.40 | 4.9 ± 2.13 | 4.3 ± 2.27 | 0.6 ± 1.68 | 0.6 ± 2.17 |
| 2 hours post-dose | 4.4 ± 2.56 | 5.2 ± 2.12 | 4.7 ± 2.30 | 0.7 ± 1.99 | 0.9 ± 2.48 |
| 3 hours post-dose | 4.3 ± 2.55 | 5.2 ± 2.28 | 4.4 ± 2.45 | 0.4 ± 1.94 | 1.1 ± 2.64 |
| 4 hours post-dose | 4.2 ± 2.54 | 5.1 ± 2.47 | 4.3 ± 2.65 | 0.6 ± 2.19 | 1.4 ± 2.99 |
| 5 hours post-dose | 4.0 ± 2.55 | 4.8 ± 2.46 | 4.1 ± 2.73 | 0.5 ± 2.11 | 1.2 ± 2.84 |
| 6 hours post-dose | 3.9 ± 2.60 | 4.6 ± 2.48 | 3.8 ± 2.74 | 0.6 ± 2.34 | 1.2 ± 3.01 |
| 7 hours post-dose | 3.8 ± 2.61 | 4.4 ± 2.56 | 3.5 ± 2.80 | 0.6 ± 2.30 | 1.2 ± 2.94 |
| 8 hours post-dose | 3.6 ± 2.63 | 4.1 ± 2.60 | 3.3 ± 2.88 | 0.6 ± 2.30 | 1.2 ± 3.00 |
| 9 hours post dose | 3.5 ± 2.72 | 3.9 ± 2.68 | 3.3 ± 2.96 | 0.6 ± 2.47 | 1.3 ± 3.15 |
| 10 hours post-dose | 3.3 ± 2.78 | 3.8 ± 2.81 | 3.1 ± 3.03 | 0.4 ± 2.25 | 1.3 ± 3.24 |
| 11 hours post-dose | 3.1 ± 2.84 | 3.6 ± 2.86 | 2.9 ± 3.02 | 0.4 ± 2.34 | 1.2 ± 3.23 |
| 12 hours post-dose | 2.9 ± 2.90 | 3.2 ± 2.90 | 2.8 ± 3.07 | 0.4 ± 2.29 | 1.3 ± 3.32 |
| 14 hours post-dose | 2.9 ± 2.97 | 2.9 ± 3.01 | 2.6 ± 3.04 | 0.4 ± 2.20 | 1.3 ± 3.32 |
| 16 hours post-dose | 2.6 ± 2.99 | 2.7 ± 2.85 | 2.4 ± 3.04 | 0.4 ± 2.27 | 1.2 ± 3.21 |
| 18 hours post-dose | 2.7 ± 3.05 | 2.6 ± 2.83 | 2.4 ± 3.02 | 0.4 ± 2.27 | 1.2 ± 3.22 |
| 20 hours post-dose | 2.7 ± 3.07 | 2.6 ± 2.81 | 2.5 ± 3.06 | 0.4 ± 2.33 | 1.2 ± 3.28 |
| 22 hours post-dose | 2.8 ± 3.19 | 2.7 ± 2.85 | 2.6 ± 3.14 | 0.5 ± 2.55 | 1.4 ± 3.51 |
| 24 hours post-dose | 2.9 ± 3.19 | 2.8 ± 2.92 | 2.6 ± 3.20 | 0.6 ± 2.62 | 1.5 ± 3.63 |
Pain Relief Score (PRS): 0 = No Relief; 1 = A Little Relief; 2 = Some Relief; 3 = A Lot of Relief; 4 = Complete Relief.
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| 0.5 hours post-dose | 1.3 ± 0.93 | 1.5 ± 1.01 | 1.5 ± 0.97 | 0.7 ± 0.72 | 0 ± 0.65 |
| 1 hour post-dose | 2.0 ± 1.04 | 2.4 ± 0.9 | 2.1 ± 0.99 | 0.7 ± 0.9 | 0.8 ± 0.96 |
| 1.5 hours post-dose | 2.3 ± 1.07 | 2.6 ± 0.87 | 2.3 ± 0.94 | 0.6 ± 0.88 | 0.8 ± 1.04 |
| 2 hours post-dose | 2.3 ± 1.13 | 2.7 ± 0.93 | 2.5 ± 0.99 | 0.7 ± 0.95 | 0.9 ± 1.17 |
| 3 hours post-dose | 2.3 ± 1.19 | 2.7 ± 1.06 | 2.4 ± 1.11 | 0.5 ± 0.93 | 1.0 ± 1.25 |
| 4 hours post-dose | 2.2 ± 1.2 | 2.6 ± 1.18 | 2.3 ± 1.2 | 0.6 ± 0.99 | 1.0 ± 1.35 |
| 5 hours post-dose | 2.1 ± 1.24 | 2.5 ± 1.13 | 2.3 ± 1.28 | 0.5 ± 1.03 | 0.8 ± 1.17 |
| 6 hours post-dose | 2.2 ± 1.26 | 2.5 ± 1.12 | 2.1 ± 1.28 | 0.6 ± 1.07 | 0.9 ± 1.3 |
| 7 hours post-dose | 2.1 ± 1.27 | 2.3 ± 1.16 | 2.0 ± 1.28 | 0.6 ± 1.07 | 0.9 ± 1.28 |
| 8 hours post-dose | 2.1 ± 1.28 | 2.2 ± 1.23 | 1.8 ± 1.36 | 0.5 ± 1.03 | 0.8 ± 1.21 |
| 9 hours post-dose | 2.0 ± 1.33 | 2.1 ± 1.28 | 1.8 ± 1.39 | 0.5 ± 1.02 | 0.8 ± 1.28 |
| 10 hours post-dose | 1.9 ± 1.35 | 2.1 ± 1.35 | 1.7 ± 1.42 | 0.5 ± 1.05 | 0.8 ± 1.31 |
| 11 hours post-dose | 1.8 ± 1.38 | 2.0 ± 1.41 | 1.6 ± 1.45 | 0.5 ± 1.07 | 0.8 ± 1.34 |
| 12 hours post-dose | 1.7 ± 1.4 | 1.8 ± 1.46 | 1.5 ± 1.47 | 0.5 ± 1.07 | 0.8 ± 1.34 |
| 14 hours post-dose | 1.6 ± 1.44 | 1.6 ± 1.51 | 1.4 ± 1.46 | 0.5 ± 1.03 | 0.8 ± 1.29 |
| 16 hours post-dose | 1.5 ± 1.45 | 1.5 ± 1.46 | 1.3 ± 1.44 | 0.5 ± 1.03 | 0.7 ± 1.25 |
| 18 hours post-dose | 1.5 ± 1.45 | 1.4 ± 1.44 | 1.3 ± 1.43 | 0.5 ± 1.03 | 0.7 ± 1.25 |
| 20 hours post-dose | 1.5 ± 1.44 | 1.4 ± 1.44 | 1.3 ± 1.46 | 0.5 ± 1.03 | 0.8 ± 1.31 |
| 22 hours post-dose | 1.5 ± 1.51 | 1.5 ± 1.50 | 1.4 ± 1.51 | 0.5 ± 1.18 | 0.9 ± 1.46 |
| 24 hours post-dose | 1.6 ± 1.53 | 1.6 ± 1.51 | 1.4 ± 1.56 | 0.5 ± 1.22 | 0.9 ± 1.51 |
The Peak Pain Intensity (peak PID) refers to the maximum change in pain intensity from baseline observed at any post-dose time point using the Numerical Rating Scale from 0 to 10. Value of 0 score means no pain and 10 score result means the worst possible pain. Participants record their pain intensity assessment in the time frame points and the highest value is identified as the Peak Pain Intensity. A high peak pain intensuty (higher value on NRS) indicates severe pain and a less effective analgesic response, and a lower value signifies better pain control and a more effective response.
| Points on scale | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Peak Pain Intensity Difference (PID) | 6.12 ± 0.11 | 6.26 ± 0.11 | 6.22 ± 0.11 | 6.30 ± 0.18 | 6.33 ± 0.19 |
Number of participants with pain relief score 4, 3, 2, 1. The Peak Pain Relief Score refers to the highest level of pain relief a participant reported at any time point during the study period. It provides an overview of the maximum effectiveness of the treatment at any given point during the observation period using the Categorical Pain Relief Scale which measure the degree of pain relief using a scale from 0 to 4, in which 0 is no relief, 1 a little relief, 2 some relief, 3 a lot of relief and 4 complete relief. A high socre closer indicates significant pain relief and reflects the effectiveness of the analgesic treatment. A score closer to 0 indicates little to no pain relief and suggests limited treatment efficacy.
| Participants | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Pain relief score 4 | 31 | 47 | 36 | 15 | 15 |
| Pain relief score 3 | 101 | 85 | 102 | 31 | 29 |
| Pain relief score 2 | 14 | 15 | 9 | 4 | 5 |
| Pain relief score 1 | 1 | 1 | 0 | 0 | 0 |
| percentage | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| 0.5 hour post-dose | 50.3 | 62.8 | 60.5 | 32.0 | 18.4 |
| less or equal 1 hour | 78.2 | 86.5 | 86.4 | 40.0 | 26.5 |
| less or equal 1.5 hour | 87.1 | 94.6 | 92.5 | 46.0 | 40.8 |
| less or equal 2 hours | 92.5 | 98.0 | 94.6 | 64.0 | 71.4 |
| less or equal 3 hours | 98.0 | 99.3 | 98.0 | 86.0 | 87.8 |
| less or equal 4 hours | 98.6 | 99.3 | 99.3 | 94.0 | 95.9 |
| less or equal 5 hours | 98.6 | 99.3 | 99.3 | 98.0 | 98.0 |
| less or equal 6 hours | 99.3 | 99.3 | 99.3 | 100 | 98.0 |
| less or equal 7 hours | 99.3 | 99.3 | 99.3 | 100 | 98.0 |
| less or equal 8 hours | 99.3 | 99.3 | 100 | 100 | 98.0 |
| less or equal 9 hours | 99.3 | 99.3 | 100 | 100 | 98.0 |
| less or equal 10 hours | 99.3 | 99.3 | 100 | 100 | 98.0 |
| less or equal 11 hours | 99.3 | 99.3 | 100 | 100 | 98.0 |
| less or equal 12 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 14 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 16 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 18 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 20 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 22 hours | 100 | 99.3 | 100 | 100 | 98.0 |
| less or equal 24 hours | 100 | 99.3 | 100 | 100 | 98.0 |
Number of participants with overall rating poor, fair, good, very good, excellent 24 hour post-dose
| Participants | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| poor | 16 | 5 | 11 | 26 | 27 |
| fair | 10 | 12 | 12 | 10 | 5 |
| good | 35 | 23 | 38 | 8 | 3 |
| very good | 56 | 69 | 58 | 5 | 9 |
| excellent | 30 | 37 | 28 | 1 | 3 |
Number of participants with at least one treatment emergent adverse event
| Participants | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Number of Participants With Adverse Events | 19 | 11 | 23 | 3 | 4 |
| Participants | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo |
|---|---|---|---|---|---|
| Bradycardia | 1 | 1 | 0 | 0 | 0 |
| Tachycardia | 1 | 0 | 3 | 0 | 0 |
| Hypertension | 2 | 0 | 0 | 0 | 0 |
| Hypotension | 1 | 3 | 4 | 0 | 0 |
Collected over All AEs and SAEs were collected from the signing of the ICF until last contact (follow-up visit at 2-5 days after discharge), an average of 5 days.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | 0/147 (0%) | 0/147 (0%) | 19/147 (12.9%) |
| Naproxen Sodium/Caffeine 2x220/65 mg | 0/148 (0%) | 0/148 (0%) | 11/148 (7.4%) |
| Placebo | 0/49 (0%) | 0/49 (0%) | 4/49 (8.2%) |
| Caffeine 100 mg | 0/50 (0%) | 0/50 (0%) | 3/50 (6%) |
| Naproxen Sodium 220 mg | 0/147 (0%) | 0/147 (0%) | 23/147 (15.6%) |
| Event | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Placebo | Caffeine 100 mg | Naproxen Sodium 220 mg |
|---|---|---|---|---|---|
| HeadacheNervous system disorders | 4/147 | 0/148 | 3/49 | 1/50 | 1/147 |
| VomitingGastrointestinal disorders | 0/147 | 0/148 | 0/49 | 0/50 | 9/147 |
| DizzinessNervous system disorders | 3/147 | 2/148 | 1/49 | 0/50 | 7/147 |
| NauseaGastrointestinal disorders | 1/147 | 6/148 | 0/49 | 0/50 | 5/147 |
| Alveolar osteitisInfections and infestations | 4/147 | 0/148 | 0/49 | 0/50 | 1/147 |
| Candida infectionInfections and infestations | 0/147 | 0/148 | 1/49 | 0/50 | 0/147 |
| HypotensionVascular disorders | 1/147 | 1/148 | 0/49 | 0/50 | 3/147 |
| TachycardiaCardiac disorders | 1/147 | 0/148 | 0/49 | 0/50 | 3/147 |
| Abdominal pain upperGastrointestinal disorders | 1/147 | 0/148 | 0/49 | 1/50 | 0/147 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/147 | 0/148 | 0/49 | 1/50 | 0/147 |
| Age, Continuous(years) | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Mean | 18.3 ± 2.13 | 18.1 ± 1.99 | 18.1 ± 1.84 | 17.7 ± 1.82 | 17.9 ± 2.05 | 18.1 ± 1.98 |
| Sex: Female, Male(Participants) | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Female | 61 | 70 | 67 | 22 | 23 | 243 |
| Male | 86 | 78 | 80 | 28 | 26 | 298 |
| Race (NIH/OMB)(Participants) | Naproxen Sodium/ Caffeine 220/65 mg | Naproxen Sodium/Caffeine 2x220/65 mg | Naproxen Sodium 220 mg | Caffeine 100 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 2 | 0 | 0 | 0 | 2 |
| Asian | 2 | 1 | 4 | 2 | 2 | 11 |
| Native Hawaiian or Other Pacific Islander | 1 | 2 | 5 | 1 | 0 | 9 |
| Black or African American | 2 | 0 | 1 | 1 | 0 | 4 |
| White | 140 | 139 | 135 | 45 | 46 | 505 |
| More than one race | 2 | 2 | 1 | 1 | 0 | 6 |
| Unknown or Not Reported | 0 | 2 | 1 | 0 | 1 | 4 |
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Plan to share: No — Availability of this study's data will later 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.vivli.org 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 member section of the portal.
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