Pain, Postoperative
Conditions
Keywords
Dental pain
Brief 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.
Interventions
DRUGNaproxen sodium/Caffeine (BAY2880376)
Tablet, oral, single dose
Tablet, oral, single dose
DRUGCaffeine
Tablet, oral, single dose
DRUGPlacebo
Tablet, oral, single dose
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference (SPID) Over 8 Hours | Up to 8 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 over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Pain Relief (TOTPAR) Over 8 Hours | Up to 8 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 over 8 hours ranges from 0 to 32, a higher value indicates more pain relief. |
| Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | Up to 2 hours, 4 hours 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 to First Use of Rescue Medication | Up to 12 hours post dose | — |
| The Cumulative Percentage of Participants Taking Rescue Medication | Up to 12 hours post dose | — |
| Pain Intensity Difference (PID) at Each Evaluation | Up to 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) From 0 to 2, 4 and 12 Hours Post-dose | Up to 2 hours, 4 hours 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. |
| Pain Relief Score at Each Evaluation | Up to 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) |
| Peak Pain Relief Score | Up to 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). 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. |
| Global Assessment of the Investigational Product | Up to 12 hours post dose | 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.' |
| Number of Participants With Adverse Events | Up to 5 days post dose | — |
| The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | Up to 5 days post dose | — |
| Peak Pain Intensity Difference (PID) | Up to 12 hours post dose | 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). |
Countries
United States
Participant flow
Recruitment details
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).
Pre-assignment details
A total of 193 participants, including 32 in each of the naproxen sodium containing groups, 16 in the caffeine group, and 17 in the placebo group, underwent dental surgery and were randomized to study drug
Participants by arm
| Arm | Count |
|---|---|
| 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 | 32 |
| 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 | 32 |
| 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 | 32 |
| 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 | 32 |
| 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 | 32 |
| Caffeine Participants received a single dose of two tablets of caffeine (medium low dose) after extraction of third molars | 16 |
| Placebo Participants received a single dose of two tablets of matching placebo after extraction of third molars | 17 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Investigator Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Naproxen Sodium/Caffeine-Dose 2 | Total | Naproxen Sodium/Caffeine-Dose 1 | Placebo | Caffeine | Naproxen Sodium | Naproxen Sodium/Caffeine-Dose 4 | Naproxen Sodium/Caffeine-Dose 3 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 17.4 years STANDARD_DEVIATION 2.42 | 17.4 years STANDARD_DEVIATION 1.86 | 17.0 years STANDARD_DEVIATION 1.03 | 17.7 years STANDARD_DEVIATION 1.4 | 17.3 years STANDARD_DEVIATION 1.7 | 17.9 years STANDARD_DEVIATION 2.74 | 17.3 years STANDARD_DEVIATION 1.49 | 17.1 years STANDARD_DEVIATION 1.34 |
| Baseline Pain Intensity Score Mild Pain (1) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Pain Intensity Score Moderate Pain (2) | 13 Participants | 70 Participants | 15 Participants | 5 Participants | 3 Participants | 11 Participants | 11 Participants | 12 Participants |
| Baseline Pain Intensity Score No Pain (0) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Pain Intensity Score Severe Pain (3) | 19 Participants | 123 Participants | 17 Participants | 12 Participants | 13 Participants | 21 Participants | 21 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 10 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 183 Participants | 30 Participants | 17 Participants | 13 Participants | 30 Participants | 29 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 14 Participants | 77 Participants | 13 Participants | 5 Participants | 5 Participants | 14 Participants | 10 Participants | 16 Participants |
| Sex: Female, Male Male | 18 Participants | 116 Participants | 19 Participants | 12 Participants | 11 Participants | 18 Participants | 22 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 6 / 32 | 3 / 32 | 1 / 32 | 2 / 32 | 3 / 32 | 5 / 16 | 4 / 17 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 16 | 0 / 17 |
Outcome results
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 35.45 Scores on a scale*hours | Standard Deviation 14.517 |
| Naproxen Sodium/Caffeine-Dose 2 | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 37.87 Scores on a scale*hours | Standard Deviation 16.876 |
| Naproxen Sodium/Caffeine-Dose 3 | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 30.70 Scores on a scale*hours | Standard Deviation 17.679 |
| Naproxen Sodium/Caffeine-Dose 4 | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 36.02 Scores on a scale*hours | Standard Deviation 14.825 |
| Naproxen Sodium | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 29.95 Scores on a scale*hours | Standard Deviation 19.067 |
| Caffeine | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 8.75 Scores on a scale*hours | Standard Deviation 21.465 |
| Placebo | Sum of Pain Intensity Difference (SPID) Over 8 Hours | 6.03 Scores on a scale*hours | Standard Deviation 17.81 |
Secondary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Global Assessment of the Investigational Product | Good (2) | 5 Participants |
| Naproxen Sodium/Caffeine-Dose 1 | Global Assessment of the Investigational Product | Poor (0) | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 1 | Global Assessment of the Investigational Product | Excellent (4) | 6 Participants |
| Naproxen Sodium/Caffeine-Dose 1 | Global Assessment of the Investigational Product | Fair (1) | 2 Participants |
| Naproxen Sodium/Caffeine-Dose 1 | Global Assessment of the Investigational Product | Very Good (3) | 18 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Global Assessment of the Investigational Product | Good (2) | 6 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Global Assessment of the Investigational Product | Fair (1) | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Global Assessment of the Investigational Product | Very Good (3) | 14 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Global Assessment of the Investigational Product | Poor (0) | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Global Assessment of the Investigational Product | Excellent (4) | 9 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Global Assessment of the Investigational Product | Excellent (4) | 5 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Global Assessment of the Investigational Product | Fair (1) | 4 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Global Assessment of the Investigational Product | Poor (0) | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Global Assessment of the Investigational Product | Good (2) | 9 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Global Assessment of the Investigational Product | Very Good (3) | 13 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Global Assessment of the Investigational Product | Good (2) | 7 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Global Assessment of the Investigational Product | Poor (0) | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Global Assessment of the Investigational Product | Fair (1) | 2 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Global Assessment of the Investigational Product | Very Good (3) | 17 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Global Assessment of the Investigational Product | Excellent (4) | 5 Participants |
| Naproxen Sodium | Global Assessment of the Investigational Product | Poor (0) | 4 Participants |
| Naproxen Sodium | Global Assessment of the Investigational Product | Excellent (4) | 3 Participants |
| Naproxen Sodium | Global Assessment of the Investigational Product | Good (2) | 6 Participants |
| Naproxen Sodium | Global Assessment of the Investigational Product | Very Good (3) | 14 Participants |
| Naproxen Sodium | Global Assessment of the Investigational Product | Fair (1) | 5 Participants |
| Caffeine | Global Assessment of the Investigational Product | Poor (0) | 8 Participants |
| Caffeine | Global Assessment of the Investigational Product | Excellent (4) | 1 Participants |
| Caffeine | Global Assessment of the Investigational Product | Very Good (3) | 2 Participants |
| Caffeine | Global Assessment of the Investigational Product | Fair (1) | 1 Participants |
| Caffeine | Global Assessment of the Investigational Product | Good (2) | 4 Participants |
| Placebo | Global Assessment of the Investigational Product | Very Good (3) | 3 Participants |
| Placebo | Global Assessment of the Investigational Product | Fair (1) | 2 Participants |
| Placebo | Global Assessment of the Investigational Product | Good (2) | 1 Participants |
| Placebo | Global Assessment of the Investigational Product | Poor (0) | 10 Participants |
| Placebo | Global Assessment of the Investigational Product | Excellent (4) | 0 Participants |
Secondary
Number of Participants With Adverse Events
Time frame: Up to 5 days post dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Number of Participants With Adverse Events | 6 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | Number of Participants With Adverse Events | 3 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | Number of Participants With Adverse Events | 1 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | Number of Participants With Adverse Events | 2 Participants |
| Naproxen Sodium | Number of Participants With Adverse Events | 3 Participants |
| Caffeine | Number of Participants With Adverse Events | 5 Participants |
| Placebo | Number of Participants With Adverse Events | 4 Participants |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 4.7 Scores on a scale | Standard Deviation 2.28 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 5.0 Scores on a scale | Standard Deviation 1.82 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 2.97 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 4.8 Scores on a scale | Standard Deviation 2.17 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 2.92 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 4.2 Scores on a scale | Standard Deviation 1.88 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 2.88 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 2.71 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 4.9 Scores on a scale | Standard Deviation 1.67 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 2.07 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 4.0 Scores on a scale | Standard Deviation 2.53 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 2.55 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 5.1 Scores on a scale | Standard Deviation 1.76 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 4.6 Scores on a scale | Standard Deviation 2.24 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 4.8 Scores on a scale | Standard Deviation 2.42 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 5.0 Scores on a scale | Standard Deviation 2.42 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 5.4 Scores on a scale | Standard Deviation 2.27 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 5.1 Scores on a scale | Standard Deviation 2.26 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 5.2 Scores on a scale | Standard Deviation 2.59 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 5.5 Scores on a scale | Standard Deviation 2.2 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 3.5 Scores on a scale | Standard Deviation 3.02 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 4.2 Scores on a scale | Standard Deviation 2.65 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 3.6 Scores on a scale | Standard Deviation 3.06 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 4.2 Scores on a scale | Standard Deviation 2.44 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 1.82 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 3.7 Scores on a scale | Standard Deviation 3.04 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 4.5 Scores on a scale | Standard Deviation 2.45 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 3.12 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 3.6 Scores on a scale | Standard Deviation 3.17 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 2.23 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 3.7 Scores on a scale | Standard Deviation 1.95 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 1.98 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 2.23 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 2.33 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 4.1 Scores on a scale | Standard Deviation 2.62 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 4.0 Scores on a scale | Standard Deviation 2.72 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 2.87 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 3.8 Scores on a scale | Standard Deviation 3.07 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 3.7 Scores on a scale | Standard Deviation 3.12 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 3.6 Scores on a scale | Standard Deviation 3 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 3.4 Scores on a scale | Standard Deviation 3.15 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 3.5 Scores on a scale | Standard Deviation 3.38 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 4.2 Scores on a scale | Standard Deviation 2.45 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 5.0 Scores on a scale | Standard Deviation 2.25 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 4.2 Scores on a scale | Standard Deviation 2.79 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 3.4 Scores on a scale | Standard Deviation 2.39 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 4.7 Scores on a scale | Standard Deviation 2.31 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 5.1 Scores on a scale | Standard Deviation 2.27 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 4.1 Scores on a scale | Standard Deviation 2.6 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 1.4 Scores on a scale | Standard Deviation 1.56 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 4.8 Scores on a scale | Standard Deviation 2.23 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 4.2 Scores on a scale | Standard Deviation 2.32 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 4.0 Scores on a scale | Standard Deviation 2.92 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 2.29 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 4.9 Scores on a scale | Standard Deviation 2.4 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 5.0 Scores on a scale | Standard Deviation 2.29 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 4.0 Scores on a scale | Standard Deviation 2.83 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 4.1 Scores on a scale | Standard Deviation 2.22 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 3.1 Scores on a scale | Standard Deviation 3.02 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 3.1 Scores on a scale | Standard Deviation 2.97 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 3.6 Scores on a scale | Standard Deviation 3.14 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 2.9 Scores on a scale | Standard Deviation 1.88 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 4.3 Scores on a scale | Standard Deviation 2.82 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 3.3 Scores on a scale | Standard Deviation 3.07 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 1.5 Scores on a scale | Standard Deviation 1.34 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 4.1 Scores on a scale | Standard Deviation 2.83 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 3.9 Scores on a scale | Standard Deviation 3.08 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 3.9 Scores on a scale | Standard Deviation 2.88 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 3.7 Scores on a scale | Standard Deviation 2.16 |
| Naproxen Sodium | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 3.7 Scores on a scale | Standard Deviation 2.96 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 3.14 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 0.98 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 2.99 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 2.85 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 3.19 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 1.3 Scores on a scale | Standard Deviation 3.11 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 1.2 Scores on a scale | Standard Deviation 2.79 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 3.36 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 2.95 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 2.67 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 1.2 Scores on a scale | Standard Deviation 2.26 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 3.09 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 3 |
| Caffeine | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 1.1 Scores on a scale | Standard Deviation 3.07 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 9 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 2.74 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 2 Hours Post-Dose | 0.5 Scores on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 5 Hours Post-Dose | 1.0 Scores on a scale | Standard Deviation 2.92 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 6 Hours Post-Dose | 1.0 Scores on a scale | Standard Deviation 3.06 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 1.5 Hours Post-Dose | 0.7 Scores on a scale | Standard Deviation 1.74 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 12 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 2.96 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 7 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 2.49 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 8 Hours Post-Dose | 0.7 Scores on a scale | Standard Deviation 2.65 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 1 Hour Post-Dose | 0.6 Scores on a scale | Standard Deviation 1.71 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 4 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 2.78 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 10 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 2.99 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 0.5 Hours Post-Dose | 0.5 Scores on a scale | Standard Deviation 0.89 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 3 Hours Post-Dose | 0.6 Scores on a scale | Standard Deviation 2.42 |
| Placebo | Pain Intensity Difference (PID) at Each Evaluation | 11 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 2.96 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 2.8 Scores on a scale | Standard Deviation 0.79 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.34 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.4 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 2.7 Scores on a scale | Standard Deviation 1.07 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.55 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.33 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.52 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 2.8 Scores on a scale | Standard Deviation 0.64 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 1.16 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.51 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 2.8 Scores on a scale | Standard Deviation 0.85 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 0.84 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 1.6 Scores on a scale | Standard Deviation 1.08 |
| Naproxen Sodium/Caffeine-Dose 1 | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 1.16 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.48 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 2.8 Scores on a scale | Standard Deviation 0.97 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 2.8 Scores on a scale | Standard Deviation 0.99 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 1.9 Scores on a scale | Standard Deviation 1.46 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 1.18 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 1.15 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.28 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 1.5 Scores on a scale | Standard Deviation 0.89 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 2.7 Scores on a scale | Standard Deviation 1.19 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 1.9 Scores on a scale | Standard Deviation 1.4 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 2.9 Scores on a scale | Standard Deviation 1.01 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.43 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.22 |
| Naproxen Sodium/Caffeine-Dose 2 | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 2.5 Scores on a scale | Standard Deviation 1.15 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.45 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.27 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.35 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 0.91 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 1.5 Scores on a scale | Standard Deviation 1.02 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 1.9 Scores on a scale | Standard Deviation 1.48 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 0.87 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 1.8 Scores on a scale | Standard Deviation 1.42 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 1.01 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.51 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 1.04 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.46 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.16 |
| Naproxen Sodium/Caffeine-Dose 3 | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.38 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.12 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 0.8 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.14 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 0.91 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 0.79 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 2.6 Scores on a scale | Standard Deviation 0.91 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 2.7 Scores on a scale | Standard Deviation 0.96 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 2.7 Scores on a scale | Standard Deviation 1 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 2.7 Scores on a scale | Standard Deviation 1.1 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 2.5 Scores on a scale | Standard Deviation 1.08 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 1.19 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 2.3 Scores on a scale | Standard Deviation 1.28 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 2.4 Scores on a scale | Standard Deviation 1.34 |
| Naproxen Sodium/Caffeine-Dose 4 | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.45 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.21 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.05 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.29 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.01 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 1.9 Scores on a scale | Standard Deviation 1.41 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.24 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 1.4 Scores on a scale | Standard Deviation 1.32 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 2.2 Scores on a scale | Standard Deviation 1.26 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 1.8 Scores on a scale | Standard Deviation 0.91 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 2.1 Scores on a scale | Standard Deviation 1.3 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 1.8 Scores on a scale | Standard Deviation 1.41 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 2.0 Scores on a scale | Standard Deviation 1.28 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 1.0 Scores on a scale | Standard Deviation 0.74 |
| Naproxen Sodium | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 1.6 Scores on a scale | Standard Deviation 1.39 |
| Caffeine | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.5 |
| Caffeine | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 1.0 Scores on a scale | Standard Deviation 1.37 |
| Caffeine | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.24 |
| Caffeine | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.33 |
| Caffeine | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.05 |
| Caffeine | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.36 |
| Caffeine | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.24 |
| Caffeine | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.36 |
| Caffeine | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1 |
| Caffeine | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
| Caffeine | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
| Caffeine | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.36 |
| Caffeine | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 0.6 Scores on a scale | Standard Deviation 0.62 |
| Caffeine | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 0.9 Scores on a scale | Standard Deviation 1.45 |
| Placebo | Pain Relief Score at Each Evaluation | 1 Hours Post-Dose | 0.6 Scores on a scale | Standard Deviation 0.81 |
| Placebo | Pain Relief Score at Each Evaluation | 5 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.18 |
| Placebo | Pain Relief Score at Each Evaluation | 3 Hours Post-Dose | 0.6 Scores on a scale | Standard Deviation 1.09 |
| Placebo | Pain Relief Score at Each Evaluation | 4 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.18 |
| Placebo | Pain Relief Score at Each Evaluation | 7 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.28 |
| Placebo | Pain Relief Score at Each Evaluation | 6 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.24 |
| Placebo | Pain Relief Score at Each Evaluation | 9 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
| Placebo | Pain Relief Score at Each Evaluation | 1.5 Hours Post-Dose | 0.6 Scores on a scale | Standard Deviation 0.73 |
| Placebo | Pain Relief Score at Each Evaluation | 11 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
| Placebo | Pain Relief Score at Each Evaluation | 2 Hours Post-Dose | 0.5 Scores on a scale | Standard Deviation 0.82 |
| Placebo | Pain Relief Score at Each Evaluation | 8 Hours Post-Dose | 0.7 Scores on a scale | Standard Deviation 1.25 |
| Placebo | Pain Relief Score at Each Evaluation | 12 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
| Placebo | Pain Relief Score at Each Evaluation | 0.5 Hours Post-Dose | 0.4 Scores on a scale | Standard Deviation 0.63 |
| Placebo | Pain Relief Score at Each Evaluation | 10 Hours Post-Dose | 0.8 Scores on a scale | Standard Deviation 1.34 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Peak Pain Intensity Difference (PID) | 6.0 Scores on a scale | Standard Deviation 1.53 |
| Naproxen Sodium/Caffeine-Dose 2 | Peak Pain Intensity Difference (PID) | 6.2 Scores on a scale | Standard Deviation 1.97 |
| Naproxen Sodium/Caffeine-Dose 3 | Peak Pain Intensity Difference (PID) | 5.9 Scores on a scale | Standard Deviation 2.01 |
| Naproxen Sodium/Caffeine-Dose 4 | Peak Pain Intensity Difference (PID) | 6.3 Scores on a scale | Standard Deviation 1.72 |
| Naproxen Sodium | Peak Pain Intensity Difference (PID) | 5.3 Scores on a scale | Standard Deviation 2.57 |
| Caffeine | Peak Pain Intensity Difference (PID) | 2.7 Scores on a scale | Standard Deviation 2.94 |
| Placebo | Peak Pain Intensity Difference (PID) | 2.3 Scores on a scale | Standard Deviation 2.98 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Peak Pain Relief Score | 3.3 Scores on a scale | Standard Deviation 0.62 |
| Naproxen Sodium/Caffeine-Dose 2 | Peak Pain Relief Score | 3.2 Scores on a scale | Standard Deviation 0.78 |
| Naproxen Sodium/Caffeine-Dose 3 | Peak Pain Relief Score | 3.0 Scores on a scale | Standard Deviation 0.82 |
| Naproxen Sodium/Caffeine-Dose 4 | Peak Pain Relief Score | 3.1 Scores on a scale | Standard Deviation 0.66 |
| Naproxen Sodium | Peak Pain Relief Score | 2.6 Scores on a scale | Standard Deviation 1.01 |
| Caffeine | Peak Pain Relief Score | 1.6 Scores on a scale | Standard Deviation 1.55 |
| Placebo | Peak Pain Relief Score | 1.3 Scores on a scale | Standard Deviation 1.39 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 50.58 Scores on a scale*hours | Standard Deviation 24.237 |
| Naproxen Sodium/Caffeine-Dose 1 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 18.02 Scores on a scale*hours | Standard Deviation 6.387 |
| Naproxen Sodium/Caffeine-Dose 1 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 8.30 Scores on a scale*hours | Standard Deviation 3.141 |
| Naproxen Sodium/Caffeine-Dose 2 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 19.26 Scores on a scale*hours | Standard Deviation 8.019 |
| Naproxen Sodium/Caffeine-Dose 2 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 8.68 Scores on a scale*hours | Standard Deviation 3.789 |
| Naproxen Sodium/Caffeine-Dose 2 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 52.45 Scores on a scale*hours | Standard Deviation 27.305 |
| Naproxen Sodium/Caffeine-Dose 3 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 44.80 Scores on a scale*hours | Standard Deviation 28.929 |
| Naproxen Sodium/Caffeine-Dose 3 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 7.17 Scores on a scale*hours | Standard Deviation 3.721 |
| Naproxen Sodium/Caffeine-Dose 3 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 15.58 Scores on a scale*hours | Standard Deviation 7.697 |
| Naproxen Sodium/Caffeine-Dose 4 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 17.05 Scores on a scale*hours | Standard Deviation 7.232 |
| Naproxen Sodium/Caffeine-Dose 4 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 6.92 Scores on a scale*hours | Standard Deviation 3.501 |
| Naproxen Sodium/Caffeine-Dose 4 | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 52.45 Scores on a scale*hours | Standard Deviation 23.022 |
| Naproxen Sodium | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 14.33 Scores on a scale*hours | Standard Deviation 8.391 |
| Naproxen Sodium | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 6.05 Scores on a scale*hours | Standard Deviation 3.511 |
| Naproxen Sodium | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 43.08 Scores on a scale*hours | Standard Deviation 30.034 |
| Caffeine | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 2.13 Scores on a scale*hours | Standard Deviation 4.06 |
| Caffeine | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 12.44 Scores on a scale*hours | Standard Deviation 32.059 |
| Caffeine | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 4.50 Scores on a scale*hours | Standard Deviation 9.604 |
| Placebo | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-12 | 1.15 Scores on a scale*hours | Standard Deviation 2.833 |
| Placebo | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-4 | 2.59 Scores on a scale*hours | Standard Deviation 7.625 |
| Placebo | Sum of Pain Intensity Differences (SPIDs) From 0 to 2, 4 and 12 Hours Post-dose | SPID 0-2 | 1.16 Scores on a scale*hours | Standard Deviation 2.925 |
Secondary
The Cumulative Percentage of Participants Taking Rescue Medication
Time frame: Up to 12 hours post dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 25.0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 15.6 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 12.5 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 25.0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 25.0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 9.4 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 1 | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 9.4 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 9.7 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 6.5 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 29.0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 25.8 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 25.8 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 6.5 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 3.2 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 9.7 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 9.7 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 3.2 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 25.8 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 6.5 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 6.3 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 9.4 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 15.6 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 18.8 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 25.0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 28.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 28.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 28.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 9.4 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 6.3 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 9.4 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 15.6 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 18.8 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 3.1 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 15.6 Percentage of participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 6.3 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 34.4 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 15.6 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 18.8 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 21.9 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 18.8 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 0 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 28.1 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 34.4 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 31.3 Percentage of participants |
| Naproxen Sodium | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 68.8 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 68.8 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 68.8 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 56.3 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 68.8 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 50 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 68.8 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 62.5 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 75.0 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 37.5 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 56.3 Percentage of participants |
| Caffeine | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 68.8 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 9 Hours Post-Dose | 75.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 11 Hours Post-Dose | 75.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 5 Hours Post-Dose | 68.8 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 1.5 Hours Post-Dose | 25.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 6 Hours Post-Dose | 68.8 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 7 Hours Post-Dose | 68.8 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 1 Hour Post-Dose | 0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 12 Hours Post-Dose | 75.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 8 Hours Post-Dose | 75.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 4 Hours Post-Dose | 68.8 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 10 Hours Post-Dose | 75.0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 0.5 Hours Post-Dose | 0 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 3 Hours Post-Dose | 56.3 Percentage of participants |
| Placebo | The Cumulative Percentage of Participants Taking Rescue Medication | 2 Hours Post-Dose | 37.5 Percentage of participants |
Secondary
The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs
Time frame: Up to 5 days post dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Naproxen Sodium/Caffeine-Dose 2 | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Naproxen Sodium/Caffeine-Dose 3 | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Naproxen Sodium/Caffeine-Dose 4 | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Naproxen Sodium | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Caffeine | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
| Placebo | The Number of Participants With Clinically Significant Changes in Physical Examinations and Vital Signs | 0 Participants |
Secondary
Time to First Use of Rescue Medication
Time frame: Up to 12 hours post dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Time to First Use of Rescue Medication | NA hours |
| Naproxen Sodium/Caffeine-Dose 2 | Time to First Use of Rescue Medication | NA hours |
| Naproxen Sodium/Caffeine-Dose 3 | Time to First Use of Rescue Medication | NA hours |
| Naproxen Sodium/Caffeine-Dose 4 | Time to First Use of Rescue Medication | NA hours |
| Naproxen Sodium | Time to First Use of Rescue Medication | NA hours |
| Caffeine | Time to First Use of Rescue Medication | 2.083 hours |
| Placebo | Time to First Use of Rescue Medication | 2.125 hours |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 28.20 Scores on a scale*hours | Standard Deviation 12.262 |
| Naproxen Sodium/Caffeine-Dose 1 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 10.27 Scores on a scale*hours | Standard Deviation 2.75 |
| Naproxen Sodium/Caffeine-Dose 1 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 4.83 Scores on a scale*hours | Standard Deviation 1.401 |
| Naproxen Sodium/Caffeine-Dose 2 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 10.29 Scores on a scale*hours | Standard Deviation 3.449 |
| Naproxen Sodium/Caffeine-Dose 2 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 4.77 Scores on a scale*hours | Standard Deviation 1.731 |
| Naproxen Sodium/Caffeine-Dose 2 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 28.26 Scores on a scale*hours | Standard Deviation 12.69 |
| Naproxen Sodium/Caffeine-Dose 3 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 25.13 Scores on a scale*hours | Standard Deviation 13.291 |
| Naproxen Sodium/Caffeine-Dose 3 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 4.22 Scores on a scale*hours | Standard Deviation 1.596 |
| Naproxen Sodium/Caffeine-Dose 3 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 8.84 Scores on a scale*hours | Standard Deviation 3.286 |
| Naproxen Sodium/Caffeine-Dose 4 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 9.28 Scores on a scale*hours | Standard Deviation 2.842 |
| Naproxen Sodium/Caffeine-Dose 4 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 3.97 Scores on a scale*hours | Standard Deviation 1.436 |
| Naproxen Sodium/Caffeine-Dose 4 | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 28.72 Scores on a scale*hours | Standard Deviation 10.678 |
| Naproxen Sodium | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 7.86 Scores on a scale*hours | Standard Deviation 3.813 |
| Naproxen Sodium | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 3.52 Scores on a scale*hours | Standard Deviation 1.644 |
| Naproxen Sodium | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 22.95 Scores on a scale*hours | Standard Deviation 13.206 |
| Caffeine | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 1.66 Scores on a scale*hours | Standard Deviation 1.767 |
| Caffeine | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 10.28 Scores on a scale*hours | Standard Deviation 13.882 |
| Caffeine | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 3.59 Scores on a scale*hours | Standard Deviation 4.148 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-12 | 8.44 Scores on a scale*hours | Standard Deviation 12.419 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-4 | 2.44 Scores on a scale*hours | Standard Deviation 3.281 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4 and 12 Hours Post-dose | TOTPAR 0-2 | 1.06 Scores on a scale*hours | Standard Deviation 1.328 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/Caffeine-Dose 1 | Total Pain Relief (TOTPAR) Over 8 Hours | 19.58 Scores on a scale*hours | Standard Deviation 7.007 |
| Naproxen Sodium/Caffeine-Dose 2 | Total Pain Relief (TOTPAR) Over 8 Hours | 20.26 Scores on a scale*hours | Standard Deviation 7.673 |
| Naproxen Sodium/Caffeine-Dose 3 | Total Pain Relief (TOTPAR) Over 8 Hours | 17.41 Scores on a scale*hours | Standard Deviation 8.063 |
| Naproxen Sodium/Caffeine-Dose 4 | Total Pain Relief (TOTPAR) Over 8 Hours | 19.53 Scores on a scale*hours | Standard Deviation 6.448 |
| Naproxen Sodium | Total Pain Relief (TOTPAR) Over 8 Hours | 16.27 Scores on a scale*hours | Standard Deviation 8.514 |
| Caffeine | Total Pain Relief (TOTPAR) Over 8 Hours | 7.03 Scores on a scale*hours | Standard Deviation 9.283 |
| Placebo | Total Pain Relief (TOTPAR) Over 8 Hours | 5.44 Scores on a scale*hours | Standard Deviation 7.709 |