Pain, Postoperative
Conditions
Keywords
Naproxen Sodium,, dental pain
Brief summary
The objective is to evaluate pain relief of the extended release naproxen sodium 660 mg tablet compared to commercial naproxen sodium 220 mg tablet over 24 hours in patients with postsurgical dental pain.
Interventions
660 mg Naproxen Sodium extended release tablet, orally administered once daily for 24 hours
DRUGNaproxen Sodium IR (Aleve, BAYH6689)
220 mg Naproxen Sodium instant release tablet, orally administered 3 times daily (TID) for 24 hours
DRUGNaproxen Sodium ER Placebo
Matching placebo of 660 mg Naproxen Sodium ER for 24 hours
DRUGNaproxen Sodium IR Placebo
Matching placebo of 220 mg Naproxen Sodium IR (Aleve) for 24 hours
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, ambulatory, male and female volunteers 15 years of age and above * Scheduled to undergo surgical removal of up to two impacted third molars, one of which must be mandibular full or partial bony impaction and the other a maxillary impaction * Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, NuvaRing, Depo-Provera, or double-barrier and have a negative pregnancy test at Screening and prior to surgery * Have not taken any form of medication or herbal supplements (ie, St. Johns Wort) within 5 days of admission (except for oral contraceptives, prophylactic antibiotics, 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 * Have not consumed alcoholic beverages, or foods and beverages containing xanthines (examples, coffee, tea, chocolate, and colas) after midnight prior to surgery and agree not to consume any of these foods or beverages throughout the evaluation period * Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without vasoconstrictor and nitrous oxide * 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 ≥ 50 mm on the 100 mm Visual Analog Scale (VAS) within 4 hours postsurgery, but no later than 1330 hours +/- 15 minutes * Understand the pain rating scales (as judged by the study coordinator) * Be willing and able to participate in all scheduled visits, treatment plan, tests and other trial procedures according to the protocol * Provide a personally signed and dated informed consent form (ICF) indicating that the subject has been informed of all pertinent aspects of the trial, (subjects \< 18 years of age must sign a written assent and have parental or guardian consent)
Exclusion criteria
* History of hypersensitivity to naproxen sodium, acetaminophen, Non Steroidal Anti-inflammatory Drugs (NSAIDS), aspirin, hydrocodone, similar pharmacological agents or components of the investigational products * Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years * Relevant concomitant disease such as asthma (exercise induced asthma is permitted), chronic sinusitis or nasal structural abnormalities causing greater than 50 percent obstruction (polyposis nasi, marked septal deviation) that can interfere with the conduct of the study in the judgment of the investigator * Current or past history of gastrointestinal bleeding or other bleeding disorder(s) * Acute illness or 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 or any other NSAIDs, Lortab, is contraindicated or use of any medications within 5 days of surgery (except oral contraceptives, prophylactic antibiotics or medications to treat benign conditions such as antibiotics to treat acne) * Females who are pregnant or lactating * Habituation to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks) * Alcoholism or drug abuse within 2 years prior to the Screening Visit or routine consumption of 3 or more alcohol containing beverages per day * Positive urine, alcohol or nicotine test on day of surgery * Smokers or using nicotine replacement therapies including transdermal patches, spray, lozenges or gum
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summed, Time-weighted Pain Intensity Difference From 0 to 24 Hours Postdose (SPID0-24) | From 0 to 24 hours post-dose | SPID0-24 was calculated by multiplying the pain intensity difference score at each post-dose timepoint by the duration (in hours) since the preceding timepoint and then summing these values over 0 to 24 hours. Pain intensity was measured at baseline, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours using the 4-point categorical pain intensity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. SPID0-24 can vary from -24 to 72. The positive SPID value indicates improvement of pain relief. The higher the SPID value, the more improvement of pain relief. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | 0-6, 0-8, 0-12, 0-16, 0-24, and 16-24 hours postdose | TOTPARs were derived by multiplying the pain relief score at each post-dose timepoint by the duration (in hours) since the preceding timepoint and then summing these values over the specified interval. Pain Relief was evaluated at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours postdose, using the 5-point overall pain relief scale: 0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief. The possible total score ranges of TOTPARs are: TOTPAR0-6: 0 to 18, TOTPAR0-8: 0 to 24, TOTPAR0-12: 0 to 36, TOTPAR0-16: 0 to 48, TOTPAR0-24: 0 to 72, TOTPAR16-24: 0 to 24. |
| Pain Intensity Differences (PIDs) by Time From Initial Dose | At 0, 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose | Pain intensity was evaluated using a 4-point Categorical Pain Intensity Rating Scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe |
| Pain Relief From Initial Dose | At 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose | Pain Relief was evaluated using the 5-point overall pain relief scale: 0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief |
| Summed, Time-weighted Pain Intensity Differences (SPID) | 0-6, 0-8, 0-12, 0-16 and 16-24 hours postdose | Pain intensity was measured at baseline, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours using the 4-point categorical pain intensity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The total possible score ranges of SPIDs are SPID0-6: -6 to 18, SPID0-8: -8 to 24, SPID0-12: -12 to 36, SPID0-16: -16 to 48, SPID16-24: -8 to 24. The positive SPID value indicates improvement of pain relief. The higher the SPID value, the more improvement of pain relief. |
| Cumulative Percentage of Participants Who Took Rescue Medication | At 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose | — |
| Number of Times the Participants Took Rescue Medication Over the 24-hour Period | 24 hours postdose | — |
| Global Assessment of the Investigational Product as a Pain Reliever | 24 hours postdose or immediately before the first intake of rescue medication | Global assessment of investigational product as a pain reliever was rated on a 5-point categorical scale: 0 = poor, 1 = fair, 2 = good, 3 = very good, 4 = excellent |
| Median Time to First Intake of Rescue Medication | Up to 24 hours postdose | Time to first use of rescue medication was estimated using Kaplan-Meier method and analyzed by a logrank test stratified by baseline pain intensity. If at least 50% of subjects in a treatment group took rescue medication, the median time to first rescue was determined for that treatment group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naproxen Sodium ER (BAYH6689) 1 naproxen sodium extended release (ER) 660 mg tablet and 1 naproxen sodium immediate release (IR) 220 mg placebo tablet initially followed by 1 naproxen sodium IR 220 mg matching placebo tablet at hour 8 (± 15 min), and 1 naproxen sodium IR 220 mg matching placebo tablet at hour 16 (± 15 min) | 120 |
| Naproxen Sodium IR (Aleve, BAYH6689) 1 naproxen sodium ER 660 mg matching placebo tablet and 1 naproxen sodium IR 220 mg tablet initially followed by 1 naproxen sodium IR 220 mg tablet at hour 8 (± 15 min), and 1 naproxen sodium IR 220 mg tablet eight hours at hour 16 (± 15 min) | 120 |
| Placebo 1 naproxen sodium ER 660 mg matching placebo tablet and 1 naproxen sodium IR 220 mg matching placebo tablet initially followed by 1 naproxen sodium IR 220 mg matching placebo tablet at hour 8 (± 15 min), and 1 naproxen sodium IR 220 mg matching placebo tablet at hour 16 (± 15 min) | 60 |
| Total | 300 |
Baseline characteristics
| Characteristic | Naproxen Sodium ER (BAYH6689) | Naproxen Sodium IR (Aleve, BAYH6689) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 24.0 Years STANDARD_DEVIATION 5.05 | 23.0 Years STANDARD_DEVIATION 4.67 | 25.0 Years STANDARD_DEVIATION 6.56 | 23.8 Years STANDARD_DEVIATION 5.28 |
| Pain Intensity Score 0 = None | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity Score 1 = Mild | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity Score 2 = Moderate | 96 Participants | 97 Participants | 53 Participants | 246 Participants |
| Pain Intensity Score 3 = Severe | 24 Participants | 23 Participants | 7 Participants | 54 Participants |
| Sex: Female, Male Female | 70 Participants | 71 Participants | 41 Participants | 182 Participants |
| Sex: Female, Male Male | 50 Participants | 49 Participants | 19 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 120 | 36 / 120 | 23 / 60 |
| serious Total, serious adverse events | 0 / 120 | 0 / 120 | 0 / 60 |
Outcome results
Primary
Summed, Time-weighted Pain Intensity Difference From 0 to 24 Hours Postdose (SPID0-24)
SPID0-24 was calculated by multiplying the pain intensity difference score at each post-dose timepoint by the duration (in hours) since the preceding timepoint and then summing these values over 0 to 24 hours. Pain intensity was measured at baseline, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours using the 4-point categorical pain intensity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. SPID0-24 can vary from -24 to 72. The positive SPID value indicates improvement of pain relief. The higher the SPID value, the more improvement of pain relief.
Time frame: From 0 to 24 hours post-dose
Population: Intent-to-treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Difference From 0 to 24 Hours Postdose (SPID0-24) | 23.2 Score on the scale | Standard Error 2.01 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Difference From 0 to 24 Hours Postdose (SPID0-24) | 23.6 Score on the scale | Standard Error 2.01 |
| Placebo | Summed, Time-weighted Pain Intensity Difference From 0 to 24 Hours Postdose (SPID0-24) | -0.6 Score on the scale | Standard Error 2.85 |
Secondary
Cumulative Percentage of Participants Who Took Rescue Medication
Time frame: At 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 12 hours | 22.5 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 3 hours | 12.5 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.75 hours | 0.0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 8 hours | 20.8 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 4 hours | 16.7 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.5 hours | 0.0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 6 hours | 20.0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 5 hours | 18.3 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 16 hours | 25.0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 1 hour | 0.0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 24 hours | 26.7 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.25 hours | 0 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 2 hours | 7.5 Percentage of participants |
| Naproxen Sodium ER (BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 20 hours | 26.7 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 12 hours | 25.8 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.25 hours | 0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.5 hours | 0.0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 0.75 hours | 0.0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 1 hour | 0.0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 2 hours | 7.5 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 3 hours | 13.3 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 4 hours | 16.7 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 5 hours | 20.0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 6 hours | 23.3 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 8 hours | 25.0 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 16 hours | 27.5 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 20 hours | 27.5 Percentage of participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Cumulative Percentage of Participants Who Took Rescue Medication | 24 hours | 27.5 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 20 hours | 66.7 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 8 hours | 63.3 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 2 hours | 30.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 1 hour | 0.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 12 hours | 66.7 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 0.75 hours | 0.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 0.25 hours | 0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 16 hours | 66.7 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 0.5 hours | 0.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 5 hours | 58.3 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 4 hours | 55.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 24 hours | 66.7 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 6 hours | 60.0 Percentage of participants |
| Placebo | Cumulative Percentage of Participants Who Took Rescue Medication | 3 hours | 50.0 Percentage of participants |
Secondary
Global Assessment of the Investigational Product as a Pain Reliever
Global assessment of investigational product as a pain reliever was rated on a 5-point categorical scale: 0 = poor, 1 = fair, 2 = good, 3 = very good, 4 = excellent
Time frame: 24 hours postdose or immediately before the first intake of rescue medication
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 3 - Very good | 33 Participants |
| Naproxen Sodium ER (BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 2 - Good | 22 Participants |
| Naproxen Sodium ER (BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 0 - Poor | 16 Participants |
| Naproxen Sodium ER (BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 1 - Fair | 14 Participants |
| Naproxen Sodium ER (BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 4 - Excellent | 35 Participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 2 - Good | 20 Participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 0 - Poor | 18 Participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 1 - Fair | 12 Participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 3 - Very good | 43 Participants |
| Naproxen Sodium IR (Aleve, BAYH6689) | Global Assessment of the Investigational Product as a Pain Reliever | 4 - Excellent | 27 Participants |
| Placebo | Global Assessment of the Investigational Product as a Pain Reliever | 4 - Excellent | 4 Participants |
| Placebo | Global Assessment of the Investigational Product as a Pain Reliever | 3 - Very good | 12 Participants |
| Placebo | Global Assessment of the Investigational Product as a Pain Reliever | 0 - Poor | 34 Participants |
| Placebo | Global Assessment of the Investigational Product as a Pain Reliever | 2 - Good | 5 Participants |
| Placebo | Global Assessment of the Investigational Product as a Pain Reliever | 1 - Fair | 5 Participants |
Secondary
Median Time to First Intake of Rescue Medication
Time to first use of rescue medication was estimated using Kaplan-Meier method and analyzed by a logrank test stratified by baseline pain intensity. If at least 50% of subjects in a treatment group took rescue medication, the median time to first rescue was determined for that treatment group.
Time frame: Up to 24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Median Time to First Intake of Rescue Medication | NA Hours |
| Naproxen Sodium IR (Aleve, BAYH6689) | Median Time to First Intake of Rescue Medication | NA Hours |
| Placebo | Median Time to First Intake of Rescue Medication | 2.9 Hours |
Secondary
Number of Times the Participants Took Rescue Medication Over the 24-hour Period
Time frame: 24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Number of Times the Participants Took Rescue Medication Over the 24-hour Period | 0.5 Rescue medication intakes | Standard Deviation 0.86 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Number of Times the Participants Took Rescue Medication Over the 24-hour Period | 0.6 Rescue medication intakes | Standard Deviation 1.02 |
| Placebo | Number of Times the Participants Took Rescue Medication Over the 24-hour Period | 1.4 Rescue medication intakes | Standard Deviation 1.2 |
Secondary
Pain Intensity Differences (PIDs) by Time From Initial Dose
Pain intensity was evaluated using a 4-point Categorical Pain Intensity Rating Scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe
Time frame: At 0, 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 12 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 3 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.75 hours, LS Mean | 1.4 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 8 hours, LS Mean | 1.3 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 4 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.5 hours, LS Mean | 1.7 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 6 hours, LS Mean | 1.3 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 5 hours, LS Mean | 1.3 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 16 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 1 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 24 hours, LS Mean | 1.1 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.25 hours, LS Mean | 1.9 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 2 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 20 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 12 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.25 hours, LS Mean | 2.0 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.5 hours, LS Mean | 1.7 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.75 hours, LS Mean | 1.5 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 1 hours, LS Mean | 1.4 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 2 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 3 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 4 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 5 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 6 hours, LS Mean | 1.3 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 8 hours, LS Mean | 1.4 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 16 hours, LS Mean | 1.2 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 20 hours, LS Mean | 1.1 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Intensity Differences (PIDs) by Time From Initial Dose | 24 hours, LS Mean | 1.1 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 20 hours, LS Mean | 2.2 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 8 hours, LS Mean | 2.3 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 2 hours, LS Mean | 2.3 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 1 hours, LS Mean | 2.1 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 12 hours, LS Mean | 2.2 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.75 hours, LS Mean | 2.0 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.25 hours, LS Mean | 2.0 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 16 hours, LS Mean | 2.2 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 0.5 hours, LS Mean | 1.9 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 5 hours, LS Mean | 2.3 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 4 hours, LS Mean | 2.3 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 24 hours, LS Mean | 2.1 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 6 hours, LS Mean | 2.3 Score on the scale |
| Placebo | Pain Intensity Differences (PIDs) by Time From Initial Dose | 3 hours, LS Mean | 2.3 Score on the scale |
Secondary
Pain Relief From Initial Dose
Pain Relief was evaluated using the 5-point overall pain relief scale: 0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief
Time frame: At 0.25, 0.5, 0.75, 1, 2, 3, 4 ,5 ,6, 8, 12, 16, 20 and 24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 20 hours | 2.3 Score on the scale | Standard Deviation 1.58 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 8 hours | 2.1 Score on the scale | Standard Deviation 1.4 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 2 hours | 2.3 Score on the scale | Standard Deviation 1.3 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 6 hours | 2.2 Score on the scale | Standard Deviation 1.37 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 3 hours | 2.3 Score on the scale | Standard Deviation 1.33 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 0.5 hours | 1.5 Score on the scale | Standard Deviation 1.08 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 5 hours | 2.3 Score on the scale | Standard Deviation 1.35 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 4 hours | 2.4 Score on the scale | Standard Deviation 1.41 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 0.25 hours | 0.9 Score on the scale | Standard Deviation 0.96 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 16 hours | 2.2 Score on the scale | Standard Deviation 1.52 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 0.75 hours | 2.0 Score on the scale | Standard Deviation 1.21 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 24 hours | 2.4 Score on the scale | Standard Deviation 1.63 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 12 hours | 2.3 Score on the scale | Standard Deviation 1.51 |
| Naproxen Sodium ER (BAYH6689) | Pain Relief From Initial Dose | 1 hour | 2.2 Score on the scale | Standard Deviation 1.29 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 8 hours | 2.0 Score on the scale | Standard Deviation 1.5 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 24 hours | 2.5 Score on the scale | Standard Deviation 1.68 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 2 hours | 2.3 Score on the scale | Standard Deviation 1.29 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 0.25 hours | 0.8 Score on the scale | Standard Deviation 0.92 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 0.5 hours | 1.3 Score on the scale | Standard Deviation 1.02 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 0.75 hours | 1.7 Score on the scale | Standard Deviation 1.14 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 1 hour | 2.0 Score on the scale | Standard Deviation 1.17 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 3 hours | 2.4 Score on the scale | Standard Deviation 1.39 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 4 hours | 2.2 Score on the scale | Standard Deviation 1.43 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 5 hours | 2.2 Score on the scale | Standard Deviation 1.49 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 6 hours | 2.2 Score on the scale | Standard Deviation 1.53 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 12 hours | 2.4 Score on the scale | Standard Deviation 1.57 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 16 hours | 2.3 Score on the scale | Standard Deviation 1.61 |
| Naproxen Sodium IR (Aleve, BAYH6689) | Pain Relief From Initial Dose | 20 hours | 2.3 Score on the scale | Standard Deviation 1.63 |
| Placebo | Pain Relief From Initial Dose | 16 hours | 1.0 Score on the scale | Standard Deviation 1.47 |
| Placebo | Pain Relief From Initial Dose | 6 hours | 0.8 Score on the scale | Standard Deviation 1.28 |
| Placebo | Pain Relief From Initial Dose | 1 hour | 0.9 Score on the scale | Standard Deviation 1.02 |
| Placebo | Pain Relief From Initial Dose | 20 hours | 1.0 Score on the scale | Standard Deviation 1.5 |
| Placebo | Pain Relief From Initial Dose | 8 hours | 0.8 Score on the scale | Standard Deviation 1.23 |
| Placebo | Pain Relief From Initial Dose | 0.75 hours | 0.9 Score on the scale | Standard Deviation 0.96 |
| Placebo | Pain Relief From Initial Dose | 0.25 hours | 0.6 Score on the scale | Standard Deviation 0.75 |
| Placebo | Pain Relief From Initial Dose | 12 hours | 0.9 Score on the scale | Standard Deviation 1.46 |
| Placebo | Pain Relief From Initial Dose | 0.5 hours | 0.8 Score on the scale | Standard Deviation 0.94 |
| Placebo | Pain Relief From Initial Dose | 4 hours | 0.9 Score on the scale | Standard Deviation 1.2 |
| Placebo | Pain Relief From Initial Dose | 3 hours | 0.7 Score on the scale | Standard Deviation 1.03 |
| Placebo | Pain Relief From Initial Dose | 24 hours | 1.2 Score on the scale | Standard Deviation 1.73 |
| Placebo | Pain Relief From Initial Dose | 5 hours | 0.9 Score on the scale | Standard Deviation 1.23 |
| Placebo | Pain Relief From Initial Dose | 2 hours | 0.8 Score on the scale | Standard Deviation 1.02 |
Secondary
Summed, Time-weighted Pain Intensity Differences (SPID)
Pain intensity was measured at baseline, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours using the 4-point categorical pain intensity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The total possible score ranges of SPIDs are SPID0-6: -6 to 18, SPID0-8: -8 to 24, SPID0-12: -12 to 36, SPID0-16: -16 to 48, SPID16-24: -8 to 24. The positive SPID value indicates improvement of pain relief. The higher the SPID value, the more improvement of pain relief.
Time frame: 0-6, 0-8, 0-12, 0-16 and 16-24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 6 hours, LS Mean | 5.3 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 8 hours, LS Mean | 7.0 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 12 hours, LS Mean | 10.9 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 16 hours, LS Mean | 14.7 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 16 to 24 hours, LS Mean | 8.5 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 8 hours, LS Mean | 6.9 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 12 hours, LS Mean | 10.9 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 16 to 24 hours, LS Mean | 8.6 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 6 hours, LS Mean | 5.3 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 16 hours, LS Mean | 15.0 Score on the scale |
| Placebo | Summed, Time-weighted Pain Intensity Differences (SPID) | From 16 to 24 hours, LS Mean | 0.4 Score on the scale |
| Placebo | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 8 hours, LS Mean | -0.8 Score on the scale |
| Placebo | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 16 hours, LS Mean | -1.0 Score on the scale |
| Placebo | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 6 hours, LS Mean | -0.5 Score on the scale |
| Placebo | Summed, Time-weighted Pain Intensity Differences (SPID) | From 0 to 12 hours, LS Mean | -0.9 Score on the scale |
Secondary
Summed, Time-weighted Total Pain Relief Scores (TOTPARs)
TOTPARs were derived by multiplying the pain relief score at each post-dose timepoint by the duration (in hours) since the preceding timepoint and then summing these values over the specified interval. Pain Relief was evaluated at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours postdose, using the 5-point overall pain relief scale: 0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief. The possible total score ranges of TOTPARs are: TOTPAR0-6: 0 to 18, TOTPAR0-8: 0 to 24, TOTPAR0-12: 0 to 36, TOTPAR0-16: 0 to 48, TOTPAR0-24: 0 to 72, TOTPAR16-24: 0 to 24.
Time frame: 0-6, 0-8, 0-12, 0-16, 0-24, and 16-24 hours postdose
Population: Intent-to-treat (ITT)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 6 hours | 13.1 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 8 hours | 17.4 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 12 hours | 26.5 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 16 hours | 35.5 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 24 hours | 54.5 Score on the scale |
| Naproxen Sodium ER (BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 16 to 24 hours | 19.0 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 16 to 24 hours | 19.4 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 6 hours | 12.8 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 16 hours | 35.8 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 24 hours | 55.1 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 8 hours | 16.8 Score on the scale |
| Naproxen Sodium IR (Aleve, BAYH6689) | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 12 hours | 26.4 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 8 hours | 6.1 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 12 hours | 9.7 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 16 to 24 hours | 8.4 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 16 hours | 13.4 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 6 hours | 4.7 Score on the scale |
| Placebo | Summed, Time-weighted Total Pain Relief Scores (TOTPARs) | From 0 to 24 hours | 21.8 Score on the scale |