Postoperative Dental Pain
Conditions
Keywords
Dental pain
Brief summary
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: * 1 fixed-dose tablet of naproxen sodium/caffeine * 2 fixed-dose tablets of naproxen sodium/caffeine * naproxen sodium only * caffeine only * or placebo The study participants will be randomly (by chance) assigned to one of the five treatment groups. They will take a single dose of two tablets by mouth within 4.5 hours after the surgery. If there is no pain relief within 2 hours after intake, other painkillers may be given.
Interventions
DRUGNaproxen sodium and caffeine (BAY2880376)
Tablet, oral use, single dose
Tablet, oral use, single dose
DRUGCaffeine
Tablet, oral use, single dose
DRUGPlacebo
Tablet, oral use, 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
Yes
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 Post-dose | Up to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | up to 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 to First Use of Rescue Medication | Up to 24 hours post-dose | — |
| The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | Up to 24 hours post-dose | — |
| Time to First Perceptible Relief Measured by a Stopwatch | Up to 24 hours post-dose | — |
| Time to Meaningful Relief Measured by a Stopwatch | Up to 24 hours post-dose | 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 to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | Up to 24 hours post-dose | — |
| Pain Intensity Difference (PID) | up to 24 hours post-dose | 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 |
| Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 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. |
| Peak Pain Intensity Difference (PID) | Up to 24 hours post-dose | 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. |
| Number of Participants With Certain Peak Pain Relief Score | Up to 24 hours post-dose | 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. |
| Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | Up to 24 hours post-dose | — |
| Global Assessment of Pain Relief of the Investigational Product | 24 hours post-dose | Number of participants with overall rating poor, fair, good, very good, excellent 24 hour post-dose |
| Number of Participants With Adverse Events | Up to 5 days post-dose | Number of participants with at least one treatment emergent adverse event |
| Number of Participants With Significant Changes in Vital Signs Since Baseline | Up to 5 days post-dose | — |
| Pain Relief Score | Up to 24 hours post-dose | Pain Relief Score (PRS): 0 = No Relief; 1 = A Little Relief; 2 = Some Relief; 3 = A Lot of Relief; 4 = Complete Relief. |
Countries
United States
Participant flow
Recruitment details
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).
Pre-assignment details
A total of 750 participants were screened at a single study center in the United States. 541 participants were randomly assigned to study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg Participants received one tablet of the fixed dose combination Naproxen sodium/Caffeine 220/65 mg and one tablet of placebo. | 147 |
| Naproxen Sodium/Caffeine 2x220/65 mg Participants received two tablets of the fixed dose combination Naproxen sodium/Caffeine 220/65 mg. | 148 |
| Naproxen Sodium 220 mg Participants received one tablet of Naproxen sodium 220 mg and one tablet of placebo. | 147 |
| Caffeine 100 mg Participants received one tablet Caffeine 100 mg one tablet of placebo. | 50 |
| Placebo Participants received two tablets of placebo. | 49 |
| Total | 541 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Naproxen Sodium/ Caffeine 220/65 mg | Total | Placebo | Caffeine 100 mg | Naproxen Sodium 220 mg | Naproxen Sodium/Caffeine 2x220/65 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 18.3 years STANDARD_DEVIATION 2.13 | 18.1 years STANDARD_DEVIATION 1.98 | 17.9 years STANDARD_DEVIATION 2.05 | 17.7 years STANDARD_DEVIATION 1.82 | 18.1 years STANDARD_DEVIATION 1.84 | 18.1 years STANDARD_DEVIATION 1.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 11 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 9 Participants | 0 Participants | 1 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 140 Participants | 505 Participants | 46 Participants | 45 Participants | 135 Participants | 139 Participants |
| Sex: Female, Male Female | 61 Participants | 243 Participants | 23 Participants | 22 Participants | 67 Participants | 70 Participants |
| Sex: Female, Male Male | 86 Participants | 298 Participants | 26 Participants | 28 Participants | 80 Participants | 78 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 0 / 148 | 0 / 49 | 0 / 50 | 0 / 147 |
| other Total, other adverse events | 19 / 147 | 11 / 148 | 4 / 49 | 3 / 50 | 23 / 147 |
| serious Total, serious adverse events | 0 / 147 | 0 / 148 | 0 / 49 | 0 / 50 | 0 / 147 |
Outcome results
Primary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 31.293 Points on scale | Standard Error 1.441 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 37.242 Points on scale | Standard Error 1.436 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 31.082 Points on scale | Standard Error 1.443 |
| Caffeine 100 mg | Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 5.146 Points on scale | Standard Error 2.47 |
| Placebo | Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose | 8.622 Points on scale | Standard Error 2.521 |
p-value: =0.00495% CI: [-9.946, -1.954]ANCOVA
p-value: =0.00395% CI: [2.161, 10.161]ANCOVA
p-value: <0.00195% CI: [20.317, 31.556]ANCOVA
p-value: =0.32595% CI: [-10.41, 3.457]ANCOVA
p-value: =0.91895% CI: [-3.798, 4.22]ANCOVA
p-value: <0.00195% CI: [26.484, 37.71]ANCOVA
p-value: <0.00195% CI: [16.753, 28.166]ANCOVA
p-value: <0.00195% CI: [20.529, 31.765]ANCOVA
p-value: <0.00195% CI: [22.921, 34.32]ANCOVA
p-value: <0.00195% CI: [16.966, 28.375]ANCOVA
Secondary
Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time
Time frame: Up to 24 hours post-dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 11 hours | 99.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 10 hours | 99.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 8 hours | 99.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 24 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 9 hours | 99.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1.5 hour | 87.1 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | 0.5 hour post-dose | 50.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 22 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 2 hours | 92.5 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 20 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 3 hours | 98.0 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 12 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 18 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 4 hours | 98.6 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1 hour | 78.2 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 16 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 5 hours | 98.6 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 14 hours | 100 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 6 hours | 99.3 percentage |
| Naproxen Sodium/ Caffeine 220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 7 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 6 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 7 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 24 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 10 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 3 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 5 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 8 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 18 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 9 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1 hour | 86.5 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 14 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1.5 hour | 94.6 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 4 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 22 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | 0.5 hour post-dose | 62.8 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 16 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 2 hours | 98.0 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 12 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 20 hours | 99.3 percentage |
| Naproxen Sodium/Caffeine 2x220/65 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 11 hours | 99.3 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1.5 hour | 92.5 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | 0.5 hour post-dose | 60.5 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1 hour | 86.4 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 2 hours | 94.6 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 3 hours | 98.0 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 4 hours | 99.3 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 5 hours | 99.3 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 6 hours | 99.3 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 7 hours | 99.3 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 8 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 9 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 10 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 11 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 14 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 16 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 18 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 20 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 22 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 24 hours | 100 percentage |
| Naproxen Sodium 220 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 12 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 18 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 14 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 12 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 2 hours | 64.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 11 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 20 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 4 hours | 94.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 6 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1.5 hour | 46.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | 0.5 hour post-dose | 32.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 16 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 8 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 22 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 9 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 5 hours | 98.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1 hour | 40.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 7 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 3 hours | 86.0 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 10 hours | 100 percentage |
| Caffeine 100 mg | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 24 hours | 100 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 10 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1 hour | 26.5 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 11 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 12 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 5 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 14 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 4 hours | 95.9 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 24 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 16 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 3 hours | 87.8 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 18 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 2 hours | 71.4 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | 0.5 hour post-dose | 18.4 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 20 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 1.5 hour | 40.8 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 8 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 9 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 7 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 22 hours | 98.0 percentage |
| Placebo | Cumulative Percent of Participants With 'at Least a 2-point PID' Over Time | less or equal 6 hours | 98.0 percentage |
Secondary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Global Assessment of Pain Relief of the Investigational Product | very good | 56 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Global Assessment of Pain Relief of the Investigational Product | poor | 16 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Global Assessment of Pain Relief of the Investigational Product | excellent | 30 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Global Assessment of Pain Relief of the Investigational Product | fair | 10 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Global Assessment of Pain Relief of the Investigational Product | good | 35 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Global Assessment of Pain Relief of the Investigational Product | very good | 69 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Global Assessment of Pain Relief of the Investigational Product | good | 23 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Global Assessment of Pain Relief of the Investigational Product | fair | 12 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Global Assessment of Pain Relief of the Investigational Product | excellent | 37 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Global Assessment of Pain Relief of the Investigational Product | poor | 5 Participants |
| Naproxen Sodium 220 mg | Global Assessment of Pain Relief of the Investigational Product | good | 38 Participants |
| Naproxen Sodium 220 mg | Global Assessment of Pain Relief of the Investigational Product | poor | 11 Participants |
| Naproxen Sodium 220 mg | Global Assessment of Pain Relief of the Investigational Product | fair | 12 Participants |
| Naproxen Sodium 220 mg | Global Assessment of Pain Relief of the Investigational Product | very good | 58 Participants |
| Naproxen Sodium 220 mg | Global Assessment of Pain Relief of the Investigational Product | excellent | 28 Participants |
| Caffeine 100 mg | Global Assessment of Pain Relief of the Investigational Product | very good | 5 Participants |
| Caffeine 100 mg | Global Assessment of Pain Relief of the Investigational Product | poor | 26 Participants |
| Caffeine 100 mg | Global Assessment of Pain Relief of the Investigational Product | excellent | 1 Participants |
| Caffeine 100 mg | Global Assessment of Pain Relief of the Investigational Product | good | 8 Participants |
| Caffeine 100 mg | Global Assessment of Pain Relief of the Investigational Product | fair | 10 Participants |
| Placebo | Global Assessment of Pain Relief of the Investigational Product | fair | 5 Participants |
| Placebo | Global Assessment of Pain Relief of the Investigational Product | excellent | 3 Participants |
| Placebo | Global Assessment of Pain Relief of the Investigational Product | very good | 9 Participants |
| Placebo | Global Assessment of Pain Relief of the Investigational Product | poor | 27 Participants |
| Placebo | Global Assessment of Pain Relief of the Investigational Product | good | 3 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Adverse Events | 19 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Adverse Events | 11 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Adverse Events | 23 Participants |
| Caffeine 100 mg | Number of Participants With Adverse Events | 3 Participants |
| Placebo | Number of Participants With Adverse Events | 4 Participants |
Secondary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 3 | 101 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 1 | 1 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 4 | 31 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 2 | 14 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 4 | 47 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 3 | 85 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 1 | 1 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 2 | 15 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 1 | 0 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 4 | 36 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 3 | 102 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 2 | 9 Participants |
| Caffeine 100 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 4 | 15 Participants |
| Caffeine 100 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 1 | 0 Participants |
| Caffeine 100 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 2 | 4 Participants |
| Caffeine 100 mg | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 3 | 31 Participants |
| Placebo | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 2 | 5 Participants |
| Placebo | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 4 | 15 Participants |
| Placebo | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 3 | 29 Participants |
| Placebo | Number of Participants With Certain Peak Pain Relief Score | Pain relief score 1 | 0 Participants |
Secondary
Number of Participants With Significant Changes in Vital Signs Since Baseline
Time frame: Up to 5 days post-dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypertension | 2 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Bradycardia | 1 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Tachycardia | 1 Participants |
| Naproxen Sodium/ Caffeine 220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypotension | 1 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Tachycardia | 0 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Bradycardia | 1 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypertension | 0 Participants |
| Naproxen Sodium/Caffeine 2x220/65 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypotension | 3 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Bradycardia | 0 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypotension | 4 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Tachycardia | 3 Participants |
| Naproxen Sodium 220 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypertension | 0 Participants |
| Caffeine 100 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Bradycardia | 0 Participants |
| Caffeine 100 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypotension | 0 Participants |
| Caffeine 100 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypertension | 0 Participants |
| Caffeine 100 mg | Number of Participants With Significant Changes in Vital Signs Since Baseline | Tachycardia | 0 Participants |
| Placebo | Number of Participants With Significant Changes in Vital Signs Since Baseline | Tachycardia | 0 Participants |
| Placebo | Number of Participants With Significant Changes in Vital Signs Since Baseline | Bradycardia | 0 Participants |
| Placebo | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypotension | 0 Participants |
| Placebo | Number of Participants With Significant Changes in Vital Signs Since Baseline | Hypertension | 0 Participants |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 11 hours post-dose | 3.1 Points on scale | Standard Deviation 2.84 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 6 hours post-dose | 3.9 Points on scale | Standard Deviation 2.6 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 0.5 hours post-dose | 1.8 Points on scale | Standard Deviation 1.89 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 12 hours post-dose | 2.9 Points on scale | Standard Deviation 2.9 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 3 hours post-dose | 4.3 Points on scale | Standard Deviation 2.55 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 22 hours post-dose | 2.8 Points on scale | Standard Deviation 3.19 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 10 hours post-dose | 3.3 Points on scale | Standard Deviation 2.78 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 5 hours post-dose | 4.0 Points on scale | Standard Deviation 2.55 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 9 hours post dose | 3.5 Points on scale | Standard Deviation 2.72 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 4 hours post-dose | 4.2 Points on scale | Standard Deviation 2.54 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 1.5 hours post-dose | 4.0 Points on scale | Standard Deviation 2.4 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 16 hours post-dose | 2.6 Points on scale | Standard Deviation 2.99 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 14 hours post-dose | 2.9 Points on scale | Standard Deviation 2.97 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 18 hours post-dose | 2.7 Points on scale | Standard Deviation 3.05 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 8 hours post-dose | 3.6 Points on scale | Standard Deviation 2.63 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | Baseline | 7.6 Points on scale | Standard Deviation 1.22 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 24 hours post-dose | 2.9 Points on scale | Standard Deviation 3.19 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 1 hour post-dose | 3.4 Points on scale | Standard Deviation 2.4 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 7 hours post-dose | 3.8 Points on scale | Standard Deviation 2.61 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 20 hours post-dose | 2.7 Points on scale | Standard Deviation 3.07 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Intensity Difference (PID) | 2 hours post-dose | 4.4 Points on scale | Standard Deviation 2.56 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 22 hours post-dose | 2.7 Points on scale | Standard Deviation 2.85 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 11 hours post-dose | 3.6 Points on scale | Standard Deviation 2.86 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 16 hours post-dose | 2.7 Points on scale | Standard Deviation 2.85 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 12 hours post-dose | 3.2 Points on scale | Standard Deviation 2.9 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 14 hours post-dose | 2.9 Points on scale | Standard Deviation 3.01 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 1.5 hours post-dose | 4.9 Points on scale | Standard Deviation 2.13 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 2 hours post-dose | 5.2 Points on scale | Standard Deviation 2.12 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | Baseline | 7.6 Points on scale | Standard Deviation 1.2 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 3 hours post-dose | 5.2 Points on scale | Standard Deviation 2.28 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 0.5 hours post-dose | 2.3 Points on scale | Standard Deviation 1.91 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 4 hours post-dose | 5.1 Points on scale | Standard Deviation 2.47 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 5 hours post-dose | 4.8 Points on scale | Standard Deviation 2.46 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 20 hours post-dose | 2.6 Points on scale | Standard Deviation 2.81 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 6 hours post-dose | 4.6 Points on scale | Standard Deviation 2.48 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 24 hours post-dose | 2.8 Points on scale | Standard Deviation 2.92 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 7 hours post-dose | 4.4 Points on scale | Standard Deviation 2.56 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 8 hours post-dose | 4.1 Points on scale | Standard Deviation 2.6 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 1 hour post-dose | 4.3 Points on scale | Standard Deviation 2.18 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 18 hours post-dose | 2.6 Points on scale | Standard Deviation 2.83 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 9 hours post dose | 3.9 Points on scale | Standard Deviation 2.68 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Intensity Difference (PID) | 10 hours post-dose | 3.8 Points on scale | Standard Deviation 2.81 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 6 hours post-dose | 3.8 Points on scale | Standard Deviation 2.74 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 10 hours post-dose | 3.1 Points on scale | Standard Deviation 3.03 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 22 hours post-dose | 2.6 Points on scale | Standard Deviation 3.14 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 24 hours post-dose | 2.6 Points on scale | Standard Deviation 3.2 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 9 hours post dose | 3.3 Points on scale | Standard Deviation 2.96 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 7 hours post-dose | 3.5 Points on scale | Standard Deviation 2.8 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 1.5 hours post-dose | 4.3 Points on scale | Standard Deviation 2.27 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 18 hours post-dose | 2.4 Points on scale | Standard Deviation 3.02 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 14 hours post-dose | 2.6 Points on scale | Standard Deviation 3.04 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 1 hour post-dose | 3.7 Points on scale | Standard Deviation 2.23 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 8 hours post-dose | 3.3 Points on scale | Standard Deviation 2.88 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 4 hours post-dose | 4.3 Points on scale | Standard Deviation 2.65 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 0.5 hours post-dose | 2.4 Points on scale | Standard Deviation 1.98 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 20 hours post-dose | 2.5 Points on scale | Standard Deviation 3.06 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 3 hours post-dose | 4.4 Points on scale | Standard Deviation 2.45 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 11 hours post-dose | 2.9 Points on scale | Standard Deviation 3.02 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 5 hours post-dose | 4.1 Points on scale | Standard Deviation 2.73 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | Baseline | 7.8 Points on scale | Standard Deviation 1.21 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 16 hours post-dose | 2.4 Points on scale | Standard Deviation 3.04 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 2 hours post-dose | 4.7 Points on scale | Standard Deviation 2.3 |
| Naproxen Sodium 220 mg | Pain Intensity Difference (PID) | 12 hours post-dose | 2.8 Points on scale | Standard Deviation 3.07 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 14 hours post-dose | 0.4 Points on scale | Standard Deviation 2.2 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | Baseline | 7.7 Points on scale | Standard Deviation 1.39 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 0.5 hours post-dose | 1.0 Points on scale | Standard Deviation 1.38 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 1 hour post-dose | 0.8 Points on scale | Standard Deviation 1.67 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 1.5 hours post-dose | 0.6 Points on scale | Standard Deviation 1.68 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 2 hours post-dose | 0.7 Points on scale | Standard Deviation 1.99 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 3 hours post-dose | 0.4 Points on scale | Standard Deviation 1.94 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 4 hours post-dose | 0.6 Points on scale | Standard Deviation 2.19 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 5 hours post-dose | 0.5 Points on scale | Standard Deviation 2.11 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 6 hours post-dose | 0.6 Points on scale | Standard Deviation 2.34 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 7 hours post-dose | 0.6 Points on scale | Standard Deviation 2.3 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 8 hours post-dose | 0.6 Points on scale | Standard Deviation 2.3 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 9 hours post dose | 0.6 Points on scale | Standard Deviation 2.47 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 10 hours post-dose | 0.4 Points on scale | Standard Deviation 2.25 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 11 hours post-dose | 0.4 Points on scale | Standard Deviation 2.34 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 12 hours post-dose | 0.4 Points on scale | Standard Deviation 2.29 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 16 hours post-dose | 0.4 Points on scale | Standard Deviation 2.27 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 18 hours post-dose | 0.4 Points on scale | Standard Deviation 2.27 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 20 hours post-dose | 0.4 Points on scale | Standard Deviation 2.33 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 22 hours post-dose | 0.5 Points on scale | Standard Deviation 2.55 |
| Caffeine 100 mg | Pain Intensity Difference (PID) | 24 hours post-dose | 0.6 Points on scale | Standard Deviation 2.62 |
| Placebo | Pain Intensity Difference (PID) | 16 hours post-dose | 1.2 Points on scale | Standard Deviation 3.21 |
| Placebo | Pain Intensity Difference (PID) | 9 hours post dose | 1.3 Points on scale | Standard Deviation 3.15 |
| Placebo | Pain Intensity Difference (PID) | 8 hours post-dose | 1.2 Points on scale | Standard Deviation 3 |
| Placebo | Pain Intensity Difference (PID) | 7 hours post-dose | 1.2 Points on scale | Standard Deviation 2.94 |
| Placebo | Pain Intensity Difference (PID) | 0.5 hours post-dose | 0.6 Points on scale | Standard Deviation 1.18 |
| Placebo | Pain Intensity Difference (PID) | 18 hours post-dose | 1.2 Points on scale | Standard Deviation 3.22 |
| Placebo | Pain Intensity Difference (PID) | 6 hours post-dose | 1.2 Points on scale | Standard Deviation 3.01 |
| Placebo | Pain Intensity Difference (PID) | 5 hours post-dose | 1.2 Points on scale | Standard Deviation 2.84 |
| Placebo | Pain Intensity Difference (PID) | 4 hours post-dose | 1.4 Points on scale | Standard Deviation 2.99 |
| Placebo | Pain Intensity Difference (PID) | Baseline | 7.7 Points on scale | Standard Deviation 0.99 |
| Placebo | Pain Intensity Difference (PID) | 20 hours post-dose | 1.2 Points on scale | Standard Deviation 3.28 |
| Placebo | Pain Intensity Difference (PID) | 3 hours post-dose | 1.1 Points on scale | Standard Deviation 2.64 |
| Placebo | Pain Intensity Difference (PID) | 2 hours post-dose | 0.9 Points on scale | Standard Deviation 2.48 |
| Placebo | Pain Intensity Difference (PID) | 1.5 hours post-dose | 0.6 Points on scale | Standard Deviation 2.17 |
| Placebo | Pain Intensity Difference (PID) | 24 hours post-dose | 1.5 Points on scale | Standard Deviation 3.63 |
| Placebo | Pain Intensity Difference (PID) | 22 hours post-dose | 1.4 Points on scale | Standard Deviation 3.51 |
| Placebo | Pain Intensity Difference (PID) | 14 hours post-dose | 1.3 Points on scale | Standard Deviation 3.32 |
| Placebo | Pain Intensity Difference (PID) | 12 hours post-dose | 1.3 Points on scale | Standard Deviation 3.32 |
| Placebo | Pain Intensity Difference (PID) | 11 hours post-dose | 1.2 Points on scale | Standard Deviation 3.23 |
| Placebo | Pain Intensity Difference (PID) | 10 hours post-dose | 1.3 Points on scale | Standard Deviation 3.24 |
| Placebo | Pain Intensity Difference (PID) | 1 hour post-dose | 0.7 Points on scale | Standard Deviation 1.89 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 7 hours post-dose | 2.1 Points on scale | Standard Deviation 1.27 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 22 hours post-dose | 1.5 Points on scale | Standard Deviation 1.51 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 11 hours post-dose | 1.8 Points on scale | Standard Deviation 1.38 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 8 hours post-dose | 2.1 Points on scale | Standard Deviation 1.28 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 1.5 hours post-dose | 2.3 Points on scale | Standard Deviation 1.07 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 10 hours post-dose | 1.9 Points on scale | Standard Deviation 1.35 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 9 hours post-dose | 2.0 Points on scale | Standard Deviation 1.33 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 0.5 hours post-dose | 1.3 Points on scale | Standard Deviation 0.93 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 2 hours post-dose | 2.3 Points on scale | Standard Deviation 1.13 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 24 hours post-dose | 1.6 Points on scale | Standard Deviation 1.53 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 20 hours post-dose | 1.5 Points on scale | Standard Deviation 1.44 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 3 hours post-dose | 2.3 Points on scale | Standard Deviation 1.19 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 1 hour post-dose | 2.0 Points on scale | Standard Deviation 1.04 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 18 hours post-dose | 1.5 Points on scale | Standard Deviation 1.45 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 4 hours post-dose | 2.2 Points on scale | Standard Deviation 1.2 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 16 hours post-dose | 1.5 Points on scale | Standard Deviation 1.45 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 5 hours post-dose | 2.1 Points on scale | Standard Deviation 1.24 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 14 hours post-dose | 1.6 Points on scale | Standard Deviation 1.44 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 6 hours post-dose | 2.2 Points on scale | Standard Deviation 1.26 |
| Naproxen Sodium/ Caffeine 220/65 mg | Pain Relief Score | 12 hours post-dose | 1.7 Points on scale | Standard Deviation 1.4 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 5 hours post-dose | 2.5 Points on scale | Standard Deviation 1.13 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 7 hours post-dose | 2.3 Points on scale | Standard Deviation 1.16 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 3 hours post-dose | 2.7 Points on scale | Standard Deviation 1.06 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 0.5 hours post-dose | 1.5 Points on scale | Standard Deviation 1.01 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 10 hours post-dose | 2.1 Points on scale | Standard Deviation 1.35 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 22 hours post-dose | 1.5 Points on scale | Standard Deviation 1.5 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 8 hours post-dose | 2.2 Points on scale | Standard Deviation 1.23 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 16 hours post-dose | 1.5 Points on scale | Standard Deviation 1.46 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 12 hours post-dose | 1.8 Points on scale | Standard Deviation 1.46 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 9 hours post-dose | 2.1 Points on scale | Standard Deviation 1.28 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 4 hours post-dose | 2.6 Points on scale | Standard Deviation 1.18 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 1.5 hours post-dose | 2.6 Points on scale | Standard Deviation 0.87 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 24 hours post-dose | 1.6 Points on scale | Standard Deviation 1.51 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 1 hour post-dose | 2.4 Points on scale | Standard Deviation 0.9 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 20 hours post-dose | 1.4 Points on scale | Standard Deviation 1.44 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 11 hours post-dose | 2.0 Points on scale | Standard Deviation 1.41 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 2 hours post-dose | 2.7 Points on scale | Standard Deviation 0.93 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 14 hours post-dose | 1.6 Points on scale | Standard Deviation 1.51 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 6 hours post-dose | 2.5 Points on scale | Standard Deviation 1.12 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Pain Relief Score | 18 hours post-dose | 1.4 Points on scale | Standard Deviation 1.44 |
| Naproxen Sodium 220 mg | Pain Relief Score | 20 hours post-dose | 1.3 Points on scale | Standard Deviation 1.46 |
| Naproxen Sodium 220 mg | Pain Relief Score | 0.5 hours post-dose | 1.5 Points on scale | Standard Deviation 0.97 |
| Naproxen Sodium 220 mg | Pain Relief Score | 1 hour post-dose | 2.1 Points on scale | Standard Deviation 0.99 |
| Naproxen Sodium 220 mg | Pain Relief Score | 1.5 hours post-dose | 2.3 Points on scale | Standard Deviation 0.94 |
| Naproxen Sodium 220 mg | Pain Relief Score | 2 hours post-dose | 2.5 Points on scale | Standard Deviation 0.99 |
| Naproxen Sodium 220 mg | Pain Relief Score | 3 hours post-dose | 2.4 Points on scale | Standard Deviation 1.11 |
| Naproxen Sodium 220 mg | Pain Relief Score | 4 hours post-dose | 2.3 Points on scale | Standard Deviation 1.2 |
| Naproxen Sodium 220 mg | Pain Relief Score | 5 hours post-dose | 2.3 Points on scale | Standard Deviation 1.28 |
| Naproxen Sodium 220 mg | Pain Relief Score | 6 hours post-dose | 2.1 Points on scale | Standard Deviation 1.28 |
| Naproxen Sodium 220 mg | Pain Relief Score | 7 hours post-dose | 2.0 Points on scale | Standard Deviation 1.28 |
| Naproxen Sodium 220 mg | Pain Relief Score | 8 hours post-dose | 1.8 Points on scale | Standard Deviation 1.36 |
| Naproxen Sodium 220 mg | Pain Relief Score | 9 hours post-dose | 1.8 Points on scale | Standard Deviation 1.39 |
| Naproxen Sodium 220 mg | Pain Relief Score | 10 hours post-dose | 1.7 Points on scale | Standard Deviation 1.42 |
| Naproxen Sodium 220 mg | Pain Relief Score | 11 hours post-dose | 1.6 Points on scale | Standard Deviation 1.45 |
| Naproxen Sodium 220 mg | Pain Relief Score | 12 hours post-dose | 1.5 Points on scale | Standard Deviation 1.47 |
| Naproxen Sodium 220 mg | Pain Relief Score | 14 hours post-dose | 1.4 Points on scale | Standard Deviation 1.46 |
| Naproxen Sodium 220 mg | Pain Relief Score | 16 hours post-dose | 1.3 Points on scale | Standard Deviation 1.44 |
| Naproxen Sodium 220 mg | Pain Relief Score | 18 hours post-dose | 1.3 Points on scale | Standard Deviation 1.43 |
| Naproxen Sodium 220 mg | Pain Relief Score | 22 hours post-dose | 1.4 Points on scale | Standard Deviation 1.51 |
| Naproxen Sodium 220 mg | Pain Relief Score | 24 hours post-dose | 1.4 Points on scale | Standard Deviation 1.56 |
| Caffeine 100 mg | Pain Relief Score | 7 hours post-dose | 0.6 Points on scale | Standard Deviation 1.07 |
| Caffeine 100 mg | Pain Relief Score | 22 hours post-dose | 0.5 Points on scale | Standard Deviation 1.18 |
| Caffeine 100 mg | Pain Relief Score | 11 hours post-dose | 0.5 Points on scale | Standard Deviation 1.07 |
| Caffeine 100 mg | Pain Relief Score | 6 hours post-dose | 0.6 Points on scale | Standard Deviation 1.07 |
| Caffeine 100 mg | Pain Relief Score | 12 hours post-dose | 0.5 Points on scale | Standard Deviation 1.07 |
| Caffeine 100 mg | Pain Relief Score | 5 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 14 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 4 hours post-dose | 0.6 Points on scale | Standard Deviation 0.99 |
| Caffeine 100 mg | Pain Relief Score | 0.5 hours post-dose | 0.7 Points on scale | Standard Deviation 0.72 |
| Caffeine 100 mg | Pain Relief Score | 16 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 3 hours post-dose | 0.5 Points on scale | Standard Deviation 0.93 |
| Caffeine 100 mg | Pain Relief Score | 18 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 2 hours post-dose | 0.7 Points on scale | Standard Deviation 0.95 |
| Caffeine 100 mg | Pain Relief Score | 1.5 hours post-dose | 0.6 Points on scale | Standard Deviation 0.88 |
| Caffeine 100 mg | Pain Relief Score | 20 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 1 hour post-dose | 0.7 Points on scale | Standard Deviation 0.9 |
| Caffeine 100 mg | Pain Relief Score | 9 hours post-dose | 0.5 Points on scale | Standard Deviation 1.02 |
| Caffeine 100 mg | Pain Relief Score | 8 hours post-dose | 0.5 Points on scale | Standard Deviation 1.03 |
| Caffeine 100 mg | Pain Relief Score | 24 hours post-dose | 0.5 Points on scale | Standard Deviation 1.22 |
| Caffeine 100 mg | Pain Relief Score | 10 hours post-dose | 0.5 Points on scale | Standard Deviation 1.05 |
| Placebo | Pain Relief Score | 1 hour post-dose | 0.8 Points on scale | Standard Deviation 0.96 |
| Placebo | Pain Relief Score | 6 hours post-dose | 0.9 Points on scale | Standard Deviation 1.3 |
| Placebo | Pain Relief Score | 2 hours post-dose | 0.9 Points on scale | Standard Deviation 1.17 |
| Placebo | Pain Relief Score | 24 hours post-dose | 0.9 Points on scale | Standard Deviation 1.51 |
| Placebo | Pain Relief Score | 11 hours post-dose | 0.8 Points on scale | Standard Deviation 1.34 |
| Placebo | Pain Relief Score | 8 hours post-dose | 0.8 Points on scale | Standard Deviation 1.21 |
| Placebo | Pain Relief Score | 5 hours post-dose | 0.8 Points on scale | Standard Deviation 1.17 |
| Placebo | Pain Relief Score | 22 hours post-dose | 0.9 Points on scale | Standard Deviation 1.46 |
| Placebo | Pain Relief Score | 18 hours post-dose | 0.7 Points on scale | Standard Deviation 1.25 |
| Placebo | Pain Relief Score | 12 hours post-dose | 0.8 Points on scale | Standard Deviation 1.34 |
| Placebo | Pain Relief Score | 10 hours post-dose | 0.8 Points on scale | Standard Deviation 1.31 |
| Placebo | Pain Relief Score | 4 hours post-dose | 1.0 Points on scale | Standard Deviation 1.35 |
| Placebo | Pain Relief Score | 0.5 hours post-dose | 0 Points on scale | Standard Deviation 0.65 |
| Placebo | Pain Relief Score | 1.5 hours post-dose | 0.8 Points on scale | Standard Deviation 1.04 |
| Placebo | Pain Relief Score | 14 hours post-dose | 0.8 Points on scale | Standard Deviation 1.29 |
| Placebo | Pain Relief Score | 7 hours post-dose | 0.9 Points on scale | Standard Deviation 1.28 |
| Placebo | Pain Relief Score | 3 hours post-dose | 1.0 Points on scale | Standard Deviation 1.25 |
| Placebo | Pain Relief Score | 9 hours post-dose | 0.8 Points on scale | Standard Deviation 1.28 |
| Placebo | Pain Relief Score | 20 hours post-dose | 0.8 Points on scale | Standard Deviation 1.31 |
| Placebo | Pain Relief Score | 16 hours post-dose | 0.7 Points on scale | Standard Deviation 1.25 |
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Peak Pain Intensity Difference (PID) | 6.12 Points on scale | Standard Error 0.11 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Peak Pain Intensity Difference (PID) | 6.26 Points on scale | Standard Error 0.11 |
| Naproxen Sodium 220 mg | Peak Pain Intensity Difference (PID) | 6.22 Points on scale | Standard Error 0.11 |
| Caffeine 100 mg | Peak Pain Intensity Difference (PID) | 6.30 Points on scale | Standard Error 0.18 |
| Placebo | Peak Pain Intensity Difference (PID) | 6.33 Points on scale | Standard Error 0.19 |
p-value: =0.33495% CI: [-0.44, 0.15]ANCOVA
p-value: =0.78395% CI: [-0.25, 0.33]ANCOVA
p-value: =0.68795% CI: [-0.5, 0.33]ANCOVA
p-value: =0.92795% CI: [-0.53, 0.49]ANCOVA
p-value: =0.49295% CI: [-0.4, 0.19]ANCOVA
p-value: =0.83695% CI: [-0.46, 0.37]ANCOVA
p-value: =0.61195% CI: [-0.53, 0.31]ANCOVA
p-value: =0.37195% CI: [-0.6, 0.22]ANCOVA
p-value: =0.75295% CI: [-0.49, 0.35]ANCOVA
p-value: =0.32195% CI: [-0.63, 0.21]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 44.207 Points on scale | Standard Error 2.266 |
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 7.347 Points on scale | Standard Error 0.341 |
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 77.596 Points on scale | Standard Error 4.949 |
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 15.899 Points on scale | Standard Error 0.688 |
| Naproxen Sodium/ Caffeine 220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 23.851 Points on scale | Standard Error 1.057 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 51.737 Points on scale | Standard Error 2.258 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 28.632 Points on scale | Standard Error 1.053 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 19.210 Points on scale | Standard Error 0.686 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 83.884 Points on scale | Standard Error 4.93 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 8.950 Points on scale | Standard Error 0.34 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 24.381 Points on scale | Standard Error 1.058 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 7.973 Points on scale | Standard Error 0.341 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 16.627 Points on scale | Standard Error 0.689 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 42.907 Points on scale | Standard Error 2.268 |
| Naproxen Sodium 220 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 72.796 Points on scale | Standard Error 4.953 |
| Caffeine 100 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 12.533 Points on scale | Standard Error 8.481 |
| Caffeine 100 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 1.876 Points on scale | Standard Error 0.585 |
| Caffeine 100 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 7.003 Points on scale | Standard Error 3.883 |
| Caffeine 100 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 4.024 Points on scale | Standard Error 1.812 |
| Caffeine 100 mg | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 2.924 Points on scale | Standard Error 1.179 |
| Placebo | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 6.308 Points on scale | Standard Error 1.849 |
| Placebo | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 13.455 Points on scale | Standard Error 3.964 |
| Placebo | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 1.567 Points on scale | Standard Error 0.597 |
| Placebo | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 28.400 Points on scale | Standard Error 8.656 |
| Placebo | Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 3.982 Points on scale | Standard Error 1.204 |
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [-2.548, -0.656]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.04395% CI: [0.029, 1.923]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [4.766, 7.427]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.71195% CI: [-1.332, 1.951]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.19695% CI: [-1.575, 0.323]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [5.744, 8.402]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [5.055, 7.757]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [4.141, 6.801]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [6.033, 8.732]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [4.43, 7.131]ANCOVA
Secondary
The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period
Time frame: Up to 24 hours post-dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 7 hours | 0.2 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 22 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 11 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 8 hours | 0.2 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1.5 hour | 0.027 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 10 hours | 0.3 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 9 hours | 0.3 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | 0.5 hour | 0 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 2 hours | 0.1 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 24 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 20 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 3 hours | 0.1 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1 hour | 0.007 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 18 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 4hours | 0.2 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 16 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 5 hours | 0.2 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 14 hours | 0.4 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 6 hours | 0.2 proportion |
| Naproxen Sodium/ Caffeine 220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 12 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 5 hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 7 hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 3 hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | 0.5 hour | 0 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 10 hours | 0.2 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 22 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 8 hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 16 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 12 hours | 0.3 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 9 hours | 0.2 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 4hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1.5 hour | 0.007 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 24 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1 hour | 0 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 20 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 11 hours | 0.3 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 2 hours | 0.034 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 14 hours | 0.4 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 6 hours | 0.1 proportion |
| Naproxen Sodium/Caffeine 2x220/65 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 18 hours | 0.4 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 20 hours | 0.5 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | 0.5 hour | 0 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1 hour | 0.007 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1.5 hour | 0.007 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 2 hours | 0.048 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 3 hours | 0.1 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 4hours | 0.1 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 5 hours | 0.1 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 6 hours | 0.2 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 7 hours | 0.2 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 8 hours | 0.3 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 9 hours | 0.3 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 10 hours | 0.4 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 11 hours | 0.4 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 12 hours | 0.4 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 14 hours | 0.4 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 16 hours | 0.5 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 18 hours | 0.5 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 22 hours | 0.5 proportion |
| Naproxen Sodium 220 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 24 hours | 0.5 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 7 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 22 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 11 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 6 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 12 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 5 hours | 0.7 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 14 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 4hours | 0.7 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | 0.5 hour | 0 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 16 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 3 hours | 0.7 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 18 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 2 hours | 0.4 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1.5 hour | 0.3 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 20 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1 hour | 0.04 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 9 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 8 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 24 hours | 0.8 proportion |
| Caffeine 100 mg | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 10 hours | 0.8 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1 hour | 0.02 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 6 hours | 0.6 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 2 hours | 0.5 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 24 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 11 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 8 hours | 0.6 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 5 hours | 0.6 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 22 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 18 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 12 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 10 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 4hours | 0.6 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | 0.5 hour | 0 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 1.5 hour | 0.2 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 14 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 7 hours | 0.6 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 3 hours | 0.5 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 9 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 20 hours | 0.7 proportion |
| Placebo | The Cumulative Proportion of Participants Taking Rescue Medication Over the 24 Hour Period | less or equal 16 hours | 0.7 proportion |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | 0.83 Hours |
| Naproxen Sodium/Caffeine 2x220/65 mg | Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | 0.76 Hours |
| Naproxen Sodium 220 mg | Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | 0.79 Hours |
| Caffeine 100 mg | Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | NA Hours |
| Placebo | Time to First Perceptible Relief Confirmed by Meaningful Relief Defined as the Time to Perceptible Pain Relief | 5.63 Hours |
p-value: =0.162ANCOVA
p-value: =0.319ANCOVA
p-value: <0.001ANCOVA
p-value: =0.343ANCOVA
p-value: =0.772ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Time to First Perceptible Relief Measured by a Stopwatch
Time frame: Up to 24 hours post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Time to First Perceptible Relief Measured by a Stopwatch | 0.39 Hours |
| Naproxen Sodium/Caffeine 2x220/65 mg | Time to First Perceptible Relief Measured by a Stopwatch | 0.35 Hours |
| Naproxen Sodium 220 mg | Time to First Perceptible Relief Measured by a Stopwatch | 0.35 Hours |
| Caffeine 100 mg | Time to First Perceptible Relief Measured by a Stopwatch | 0.60 Hours |
| Placebo | Time to First Perceptible Relief Measured by a Stopwatch | 1.93 Hours |
p-value: =0.647ANCOVA
p-value: =0.714ANCOVA
p-value: =0.065ANCOVA
p-value: =0.742ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Time to First Use of Rescue Medication
Time frame: Up to 24 hours post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Time to First Use of Rescue Medication | NA Hours |
| Naproxen Sodium/Caffeine 2x220/65 mg | Time to First Use of Rescue Medication | NA Hours |
| Naproxen Sodium 220 mg | Time to First Use of Rescue Medication | 19.72 Hours |
| Caffeine 100 mg | Time to First Use of Rescue Medication | 2.07 Hours |
| Placebo | Time to First Use of Rescue Medication | 2.65 Hours |
p-value: =0.963ANCOVA
p-value: =0.118ANCOVA
p-value: <0.001ANCOVA
p-value: =0.244ANCOVA
p-value: =0.139ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Time to Meaningful Relief Measured by a Stopwatch | 0.83 Hours |
| Naproxen Sodium/Caffeine 2x220/65 mg | Time to Meaningful Relief Measured by a Stopwatch | 0.76 Hours |
| Naproxen Sodium 220 mg | Time to Meaningful Relief Measured by a Stopwatch | 0.79 Hours |
| Caffeine 100 mg | Time to Meaningful Relief Measured by a Stopwatch | NA Hours |
| Placebo | Time to Meaningful Relief Measured by a Stopwatch | 5.63 Hours |
p-value: =0.162ANCOVA
p-value: =0.319ANCOVA
p-value: <0.001ANCOVA
p-value: =0.343ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 3.284 Points on scale | Standard Error 0.114 |
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 7.781 Points on scale | Standard Error 0.287 |
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 12.098 Points on scale | Standard Error 0.465 |
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-8 hours post-dose | 16.227 Points on scale | Standard Error 0.645 |
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 23.512 Points on scale | Standard Error 1.029 |
| Naproxen Sodium/ Caffeine 220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 41.596 Points on scale | Standard Error 2.281 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 26.461 Points on scale | Standard Error 1.026 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 43.908 Points on scale | Standard Error 2.272 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 3.870 Points on scale | Standard Error 0.114 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 14.061 Points on scale | Standard Error 0.464 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-8 hours post-dose | 18.625 Points on scale | Standard Error 0.642 |
| Naproxen Sodium/Caffeine 2x220/65 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 9.118 Points on scale | Standard Error 0.286 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-8 hours post-dose | 16.225 Points on scale | Standard Error 0.645 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 22.767 Points on scale | Standard Error 1.03 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 3.417 Points on scale | Standard Error 0.115 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 12.420 Points on scale | Standard Error 0.466 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 8.102 Points on scale | Standard Error 0.287 |
| Naproxen Sodium 220 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 39.127 Points on scale | Standard Error 2.283 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-8 hours post-dose | 4.327 Points on scale | Standard Error 1.105 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 2.120 Points on scale | Standard Error 0.492 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 3.228 Points on scale | Standard Error 0.798 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 12.047 Points on scale | Standard Error 3.909 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 6.264 Points on scale | Standard Error 1.764 |
| Caffeine 100 mg | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 1.047 Points on scale | Standard Error 0.196 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-12 hours post-dose | 9.700 Points on scale | Standard Error 1.801 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-6 hours post-dose | 4.870 Points on scale | Standard Error 0.814 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-4 hours post-dose | 3.168 Points on scale | Standard Error 0.502 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-24 hours post-dose | 18.975 Points on scale | Standard Error 3.99 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-8 hours post-dose | 6.552 Points on scale | Standard Error 1.128 |
| Placebo | Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose | 0-2 hours post-dose | 1.216 Points on scale | Standard Error 0.2 |
Comparison: 0-6 hours post-dosep-value: =0.1595% CI: [-3.881, 0.597]ANCOVA
Comparison: 0-6 hours post-dosep-value: =0.62595% CI: [-1.617, 0.972]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [9.02, 12.645]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [5.707, 9.392]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [-0.903, -0.269]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.00595% CI: [0.136, 0.771]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [1.923, 2.815]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.54895% CI: [-0.719, 0.382]ANCOVA
Comparison: 0-2 hours post-dosep-value: =0.41595% CI: [-0.451, 0.186]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [2.377, 3.268]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [1.748, 2.654]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [1.791, 2.683]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [2.202, 3.106]ANCOVA
Comparison: 0-2 hours post-dosep-value: <0.00195% CI: [1.615, 2.521]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [-2.133, -0.542]ANCOVA
Comparison: 0-4 hours post-dosep-value: =0.01295% CI: [0.22, 1.813]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [4.864, 7.101]ANCOVA
Comparison: 0-4 hours post-dosep-value: =0.13695% CI: [-2.428, 0.332]ANCOVA
Comparison: 0-4 hours post-dosep-value: =0.4395% CI: [-1.119, 0.477]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [5.881, 8.116]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [3.798, 6.07]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [4.543, 6.779]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [4.816, 7.085]ANCOVA
Comparison: 0-4 hours post-dosep-value: <0.00195% CI: [3.478, 5.749]ANCOVA
Comparison: 0-6 hours post-dosep-value: =0.00395% CI: [-3.254, -0.673]ANCOVA
Comparison: 0-6 hours post-dosep-value: =0.01395% CI: [0.35, 2.933]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [7.377, 11.006]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [7.055, 10.683]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [7.351, 11.031]ANCOVA
Comparison: 0-6 hours post-dosep-value: <0.00195% CI: [5.386, 9.07]ANCOVA
Comparison: 0-8 hours post-dosep-value: =0.00995% CI: [-4.185, -0.61]ANCOVA
Comparison: 0-8 hours post-dosep-value: =0.00995% CI: [0.61, 4.189]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [9.384, 14.412]ANCOVA
Comparison: 0-8 hours post-dosep-value: =0.15995% CI: [-5.327, 0.877]ANCOVA
Comparison: 0-8 hours post-dosep-value: =0.99895% CI: [-1.792, 1.795]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [11.787, 16.809]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [7.12, 12.226]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [9.387, 14.413]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [9.523, 14.623]ANCOVA
Comparison: 0-8 hours post-dosep-value: <0.00195% CI: [7.123, 12.227]ANCOVA
Comparison: 0-12 hours post-dosep-value: =0.04395% CI: [-5.803, -0.095]ANCOVA
Comparison: 0-12 hours post-dosep-value: =0.01195% CI: [0.837, 6.55]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [12.49, 20.517]ANCOVA
Comparison: 0-12 hours post-dosep-value: =0.17395% CI: [-8.389, 1.515]ANCOVA
Comparison: 0-12 hours post-dosep-value: =0.6195% CI: [-2.119, 3.608]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [16.189, 24.206]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [8.992, 17.143]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [13.236, 21.261]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [12.69, 20.831]ANCOVA
Comparison: 0-12 hours post-dosep-value: <0.00195% CI: [9.738, 17.886]ANCOVA
Comparison: 0-24 hours post-dosep-value: =0.47395% CI: [-8.635, 4.011]ANCOVA
Comparison: 0-24 hours post-dosep-value: <0.00195% CI: [18.188, 35.973]ANCOVA
Comparison: 0-24 hours post-dosep-value: =0.21595% CI: [-17.9, 4.044]ANCOVA
Comparison: 0-24 hours post-dosep-value: =0.44595% CI: [-3.876, 8.813]ANCOVA
Comparison: 0-24 hours post-dosep-value: <0.00195% CI: [11.122, 29.183]ANCOVA
Comparison: 0-24 hours post-dosep-value: <0.00195% CI: [15.914, 33.952]ANCOVA
Comparison: 0-24 hours post-dosep-value: <0.00195% CI: [13.594, 31.648]ANCOVA