Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Naproxen Sodium 660mg, Naproxen Sodium ER (BAY117031), 20% HPMC, Naproxen, 20% HPMC, Naproxen sodium, Naproxen and diphenhydramine soft, Naproxen (BAYH006689), Naproxen Sodium, (BAY H6689), Naproxen Sodium (Aleve, BAY117031)
Naproxen · 22 trials · 12 indications
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.
WASO was defined as Total wake time (in minutes) after sleep onset during the 10 hours in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.
Sleep latency was defined as the time to sleep onset from the time of dosing as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.
The primary objective of this trial was to determine the percentage of non-therapeutic misuse. Two aspects of consumer use of Aleve 24 Hour were examined: the frequency at which consumers exceeded the label-defined daily dose modified by those who did so for non-therapeutic reasons.
Participants were instructed to select a product for use upon their pain episode and then call a toll-free number for an interview within 30 minutes of the selection decision. Participants who did not call were interviewed after 14 days for data collection. The primary endpoint was derived from 2 variables: 1) number of participants who selected Naproxen Sodium ER and reported expected duration of pain less than or equal to 12 hrs (A); 2) number of participants who selected Naproxen Sodium ER and report expected duration of pain greater than 12 hrs (B). The results was calculated as B/(A+B).
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.
Please see further details in Adverse Events (AE) section
Please see further details in AE section
Misuse occasion: any reported use of 2 or more tablets within a 22 hour period (included use of 2 tablets in 1 dose or the use of 1 tablet at one time and 1+ tablets at a later time within the same 22 hour period). Use-days were calculated based on days in which there was subject-reported product consumption, meaning that if a tablet was consumed on a day this resulted in 1 use-day. If a subject reported product consumption on 3 different days this resulted in 3 use-days. The cumulative expression of use-days is the total number of use-days reported by all subjects with follow up data.
Categorical pain intensity scale - no pain (0), mild pain (1), moderate pain (2), or severe pain (3) was used for all pain intensity assessments postdose. Time-weighted Sum Pain Intensity Difference (SPID) was calculated by multiplying the Pain Intensity Difference (PID) score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values over 0-24 and 16-24 hours, respectively.
Algometry area under the curve (AUC) from zero to the initial 72h post dose. The 72h AUC algometry data was an aggregate of all measurements from timepoints and data including the 72h timepoint. The average data of all participants was reported.
Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction.
Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. This endpoint was calculated by summing the changes from baseline (CFB) in BASS scores at Days 2, 3, and 4 of the treatment periods.
Skin sensitization will be based on specific scoring criteria.
Area under the concentration vs. time curve from zero to infinity after single (first) dose
Area under plasma concentration vs. time curve from zero to last data point \>LLOQ (lower limit of quantitation), calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule
Maximum observed drug concentration, directly observed from analytical data
Inhibition of serum TXB2 at specified time point was calculated using the percentage of reduction from baseline as follows: Inhibition (%) = 100 × (Baseline Value - Post-baseline Value) / Baseline Value. For primary analysis, the mean and the lower bound of the corresponding one-sided 95% Confidence Interval (CI) were calculated.
| Arm | Type | Description |
|---|---|---|
| Naproxen sodium/caffeine - Dose 1 | EXPERIMENTAL | Participants will receive a single dose of one tablet of naproxen sodium/caffeine plus one tablet of placebo after extraction of third molars. |
| Naproxen sodium/caffeine - Dose 2 | EXPERIMENTAL | Participants will receive a single dose of two tablets of naproxen sodium/caffeine after extraction of third molars. |
| Naproxen sodium | EXPERIMENTAL | Participants will receive a single dose of one tablet of naproxen sodium plus one tablet of placebo after extraction of third molars. |
| Caffeine | EXPERIMENTAL | Participants will receive a single dose of two tablets of caffeine after extraction of third molars. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive a single dose of two tablets of matching placebo after extraction of third molars. |
| Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) | EXPERIMENTAL | - |
| Naproxen Sodium 440 mg (BAYH6689) | ACTIVE_COMPARATOR | - |
| DPH 50 mg | ACTIVE_COMPARATOR | - |
| Arm 1 | EXPERIMENTAL | - |
| Naproxen Sodium ER (BAYH6689) or Advil IR | EXPERIMENTAL | Eligible subjects were provided with 24 Advil immediate-release (IR) caplets containing 200 mg Ibuprofen and Naproxen Sodium extended release (ER) tablets containing 660 mg Naproxen Sodium. Upon a single incidence of pain, subjects were instructed to review both packages and choose one product to use. Subject were not offered any additional instructions for use beyond what is on the packages. |
| Naproxen Sodium ER (BAYH6689) | EXPERIMENTAL | 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) |
| Naproxen Sodium IR (Aleve, BAYH6689) | ACTIVE_COMPARATOR | 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) |
| Naproxen sodium 440 mg/DPH 50 mg (BAY98-7111) | EXPERIMENTAL | - |
| Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111) | EXPERIMENTAL | - |
| Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111) | EXPERIMENTAL | - |
| Naproxen Topical Gel (BAYH006689) | EXPERIMENTAL | UI Number: 1614000-268; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). |
| Diclofenac Diethylamine Gel | ACTIVE_COMPARATOR | UI Number: Not applicable; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). |
| Placebo Gel | PLACEBO_COMPARATOR | UI Number: 1614000-272; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). |
| Naproxen sodium/caffeine - Dose 3 | EXPERIMENTAL | Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ medium low dose) plus one tablet of placebo after extraction of third molars |
| Naproxen sodium/caffeine - Dose 4 | EXPERIMENTAL | Participants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ low dose) plus one tablet of placebo after extraction of third molars |
| Treatment A-D-C-B | EXPERIMENTAL | Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by placebo for 4 days; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days. |
| Treatment B-C-D-A | EXPERIMENTAL | Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by placebo for 4 days; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days. |
| Treatment C-A-B-D | EXPERIMENTAL | Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by placebo for 4 days. Treatment periods were separated by a washout period of 3 to 7 days. |
| Treatment D-B-A-C | EXPERIMENTAL | Participants received placebo for 4 days; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days |
| BAYHO06689 | EXPERIMENTAL | Topical application of BAYH006689 naproxen 10% topical gel on the intact skin |
| Negative control | PLACEBO_COMPARATOR | Topical application of the sterile 0.9% saline (negative control) on the intact skin |
| Positive control | ACTIVE_COMPARATOR | Topical application of the 0.2% sodium lauryl sulfate (SLS) (positive control) on the intact skin |
| Test product + Reference product | EXPERIMENTAL | Each treatment sequence consists of two treatment periods (Dosing Periods 1 and 2) with each period consisting of 4 days starting with an overnight fast of at least 10 hours. Subjects will consume a standardized high calorie, high fat breakfast approximately 30 minutes prior to dosing followed by a single dose of study drug administration the morning of Day 1, then a 72-hour PK blood sampling period. The two study drug administrations are separated by a 7 calendar days washout phase. |
| Reference product + Test product | EXPERIMENTAL | Each treatment sequence consists of two treatment periods (Dosing Periods 1 and 2) with each period consisting of 4 days starting with an overnight fast of at least 10 hours. Subjects will consume a standardized high calorie, high fat breakfast approximately 30 minutes prior to dosing followed by a single dose of study drug administration the morning of Day 1, then a 72-hour PK blood sampling period. The two study drug administrations are separated by a 7 calendar days washout phase. |
| IR ASA co-administered with naproxen sodium | EXPERIMENTAL | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg once daily (qd) in parallel with naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| IR ASA 30 min after naproxen sodium | EXPERIMENTAL | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes after naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| IR ASA 8 hours after naproxen sodium | EXPERIMENTAL | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 8 hours after naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| IR ASA only | ACTIVE_COMPARATOR | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| IR ASA 30 min before naproxen sodium | EXPERIMENTAL | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes before naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| IR ASA 30 min after first dose of naproxen sodium bid | EXPERIMENTAL | Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes after first dose of naproxen sodium (Aleve, BAY117031) 220 mg, followed by second dose of naproxen sodium 220 mg 12 hours after first dose, for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. |
| Arm 2 | ACTIVE_COMPARATOR | - |
| Naproxen sodium extended release 660 mg, 20% HPMC | EXPERIMENTAL | Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve (Naproxen sodium) 220 mg tablet |
| Naproxen sodium extended release 660 mg, 30% HPMC | EXPERIMENTAL | Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve 220 mg tablet |
| Naproxen sodium extended release 660 mg, 40% HPMC | EXPERIMENTAL | Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve 220 mg tablet |
| Naproxen sodium 220 mg | ACTIVE_COMPARATOR | Bioequivalence in healthy adult subjects in a fasted state |
| Name | Type | Description |
|---|---|---|
| Naproxen sodium and caffeine (BAY2880376) | DRUG | Tablet, oral use, single dose |
| Naproxen sodium (Aleve) | DRUG | Tablet, oral use, single dose |
| Caffeine | DRUG | Tablet, oral use, single dose |
| Placebo | DRUG | Tablet, oral use, single dose |
| Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) | DRUG | Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally. |
| Naproxen Sodium 440 mg (BAYH6689) | DRUG | Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally. |
| DPH 50 mg | DRUG | Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally. |
| Naproxen Sodium ER (BAYH6689) | DRUG | BAYH6689; oral tablet used as needed upon incidence of pain |
| Advil | DRUG | Commercially available Advil; oral caplet upon incidence of pain |
| Naproxen Sodium IR (Aleve, BAYH6689) | DRUG | 220 mg Naproxen Sodium instant release tablet, orally administered 3 times daily (TID) for 24 hours |
| Naproxen Sodium ER Placebo | DRUG | Matching placebo of 660 mg Naproxen Sodium ER for 24 hours |
| Naproxen Sodium IR Placebo | DRUG | Matching placebo of 220 mg Naproxen Sodium IR (Aleve) for 24 hours |
| Naproxen sodium 440 mg/DPH 50 mg (BAY98-7111) | DRUG | 2 capsules each containing naproxen sodium 220 mg /diphenhydramine hydrochloride (DPH) 25 mg are taken orally with a full glass of water approximately 30 minutes prior to bedtime for 10 consecutive days |
| Naproxen sodium 440 mg / DPH 50 mg (BAY98-7111) | DRUG | Participants received two Naproxen sodium 220 mg / DPH (Diphenhydramine hydrochloride) 25 mg tablets orally, single dose |
| Naproxen sodium 220 mg / DPH 50 mg (BAY98-7111) | DRUG | Participants received one Naproxen sodium 220 mg / DPH 50 mg tablet and one matching placebo capsule orally, single dose |
| Naproxen gel | DRUG | 10%, bid for 5 days (final application on morning of Day 6) |
| Diclofenac gel | DRUG | 2.32% bid for 5 days (final application on morning of Day 6) |
| Placebo gel | DRUG | bid for 5 days (final application on morning of Day 6) |
| Naproxen sodium/Caffeine (BAY2880376) | DRUG | Tablet, oral, single dose |
| Naproxen Sodium (Aleve, BAY117031) | DRUG | 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A) |
| Acetaminophen ER | DRUG | 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B) |
| Celecoxib | DRUG | 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C) |
| Naproxen (BAYH006689) | DRUG | BAYH006689 gel will be dispensed directly on the patch |
| A solution of 0.9% Saline | DRUG | 0.9% Saline will be dispensed directly on the patch |
| A solution of 0.2% SLS | DRUG | 0.2% SLS will be dispensed directly on the patch. |
| Naproxen sodium and diphenhydramine hydrochloride soft capsules | DRUG | Single oral administration of Naproxen sodium 220 mg/DPH HCl 25mg (2 capsules) |
| Naproxen sodium and diphenhydramine hydrochloride coated tablets (Aleve PM, BAY98-7111) | DRUG | Single administration of Naproxen sodium 220 mg/DPH HCl 25mg (2 tablets) |
| Naproxen sodium and diphenhydramine hydrochloride coated tablets (Aleve, PMBAY98-7111) | DRUG | Single administration of Naproxen sodium 220 mg/DPH HCl 25mg (2 tablets) |
| Acetylsalicylic Acid (Aspirin, BAYE4465) | DRUG | ASA 81 mg qd |
| Naproxen Sodium, (BAY H6689) | DRUG | One dose of Naproxen sodium extended release 660 mg under fasting conditions |
| Naprelan, (BAY H6689) | DRUG | One dose of Naprelan 500 mg (2 tablets) under fasting conditions |
| Commercial Naproxen (Aleve, BAYH6689) | DRUG | Immediate release Commercial Aleve (220mg) administered in a two ( 440 mg) plus one (220mg) dosing regime, 660 mg daily |
| Naproxen Sodium 660mg | DRUG | Extended release Naproxen Sodium (660mg) administered once a day |
| Commercial Aleve 220 mg | DRUG | Immediate release commercial Aleve (220 mg) administered in a 2 (440 mg) plus one (220 mg) dosing schedule, 660 mg total |
| Naproxen sodium | DRUG | Administered under fasting condition |
| Naproxen Sodium ER (BAY117031), 20% HPMC | DRUG | 1 tablet 660 mg administered orally once daily |
| Naproxen Sodium ER (BAY117031), 30% HPMC | DRUG | 1 tablet 660 mg administered orally once daily |
| Naproxen Sodium ER (BAY117031), 40% HPMC | DRUG | 1 tablet 660 mg administered orally once daily |
| Aleve (Naproxen Sodium, BAY117031) | DRUG | 1 tablet 220 mg administered orally three times daily |
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,...