Pain
Conditions
Keywords
third molar extraction, ibuprofen, ibuprofen/caffeine, post-surgical dental pain
Brief summary
An efficacy study assessing analgesic effect of ibuprofen/caffeine in post-surgical dental pain.
Detailed description
The purpose of this study is to assess the analgesic efficacy of a fixed dose combination of ibuprofen/caffeine compared to ibuprofen alone and also to placebo.
Interventions
DRUGIbuprofen/Caffeine
Ibuprofen/Caffeine fixed-dose combination
DRUGIbuprofen
Ibuprofen capsule
DRUGPlacebo
Placebo treatment
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 16 years to 40 years of age (inclusive). * Subjects who have undergone outpatient surgical extraction of 3 or more third molars, of which at least 2 must be a partial or complete bony mandibular impaction within 30 days of Screening and have met baseline pain criteria as described in this protocol * Examined by the attending dentist or physician and medically cleared to participate in the study.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) determined by the Investigator to place the subject at increased risk including the presence or history within 2 years of screening of the following medical conditions/disorders: * Bleeding disorder; * Gastrointestinal ulcer or gastrointestinal bleeding; * Paralytic ileus or other gastrointestinal obstructive disorders. * Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception * Hypersensitivity to ibuprofen, naproxen, aspirin, or any other NSAID, caffeine, or other component of the product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Weighted Sum of Pain Relief Rating (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen | From 0 to 8 hours post-dose on Day 1 | SPRID 0-8: time-weighted sum of PRID scores from 0 to 8 hours. PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Numerical pain severity rating (NPSR) scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible SPRID 0-8 score range: -80 to 112, higher scores = more improvement in pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | TOTPAR 0-2, TOTPAR 0-4, TOTPAR 0-6, TOTPAR 0-8: time-weighted sum of PRR scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. PRR score: at each post-dose time point participants answered to the question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Overall possible range: TOTPAR 0-2 = 0 to 8; TOTPAR 0-4 = 0 to 16; TOTPAR 0-6 = 0 to 24; TOTPAR 0-8 = 0 to 32. Higher TOTPAR scores = more improvement in pain. |
| Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1 | PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. |
| Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1 | NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a single post-dose time point: -10 to 10, higher positive value = greater improvement in pain. |
| Time to Onset of Achieving Meaningful Relief | Up to 8 hours post-dose on Day 1 | When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as meaningful relief at the moment when they first experienced meaningful relief, that is, when the relief from the pain was meaningful to them. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered). |
| Time to Onset of First Perceptible Relief | Up to 8 hours post-dose on Day 1 | When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as first perceptible relief at the moment when they first began to feel any pain relieving effect. It was when they first felt a little/noticeable pain relief. It did not mean that they felt completely better (though they might), but when they first felt any difference in pain that they had at present. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered). |
| Time to Treatment Failure | Up to 8 hours post dose on Day 1 | Treatment failure was defined as time to first dose of rescue medication or study discontinuation of the participants due to lack of efficacy. |
| Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | SPRID 0-2, SPRID 0-4, SPRID 0-6, SPRID 0-8: time-weighted sum of PRID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours respectively. PRID at each post-dose time point = PID + PRR. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on 5-point scale: 0=none, 1=a little, 2=some, 3=a lot, 4=complete; higher scores=more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on 11-point scale: range from 0=no pain to 10=worst possible pain; higher scores=worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value=greater improvement. Score range for: SPRID 0-2= -20 to 28; SPRID 0-4= -40 to 56; SPRID 0-6= -60 to 84; SPRID 0-8= -80 to 112. Higher SPRID scores=more improvement in pain. |
| Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | SPID 0-2, SPID 0-4, SPID 0-6, SPID 0-8: time-weighted sum of PID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: score range from 0 = no pain to 10 = worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible range: SPID 0-2 = -20 to 20; SPID 0-4 = -40 to 40; SPID 0-6 = -60 to 60; SPID 0-8 = -80 to 80. Higher SPID scores = more improvement in pain. |
| Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose on Day 1 | PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. At a single post-dose time point overall possible range for PRID score: -10 to 14, higher scores = more improvement in pain. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days) | Vital signs included: heart rate, blood pressure, respiratory rate, and temperature. Normal range for the vital signs were: systolic blood pressure 90 to 140 millimeter of mercury (mmHg), diastolic blood pressure 60 to 90 mmHg, heart rate 50 to 110 beats per minute, respiratory rate 12 to 22 breaths per minute, and oral temperature 97.0 to 99.6 Fahrenheit (F). Value for vital signs outside the normal range was consider as abnormal. Clinical significance of vital signs abnormalities was determined at the investigator's discretion. |
| Number of Participants Who Used Concomitant Medications, and Rescue Medications | Day 1 | Rescue medication: participants who did not experience adequate relief after the 1 hour (post study drug dose) evaluation were given tramadol hydrochloride 50 to 100 mg orally or codeine sulfate 15 to 60 mg orally, based on the discretion of the Investigator, as rescue medication. If needed, 2 additional doses of rescue medications based on the discretion of the Investigator at the study center was given. Total maximum dose of tramadol was 300 mg and of codeine sulfate was 180 mg. Concomitant medication: medication received by participant other than study medication and rescue medication. |
| Number of Participants Who Used Medications Prior to This Study | At Screening | In this outcome measure number of participants who were using any type of medications, prior to start of the study were reported. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs are classified according to severity in 3 categories as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). |
| Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs) | Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. Relatedness of an AE to study drug was assessed by investigator. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg Participants were randomized to receive a single oral dose of ibuprofen 400 mg with caffeine 100 mg as a fixed dose combination on Day 1. Participants were followed up to 17 days after the last dose of study drug. | 161 |
| Ibuprofen 400 mg Participants were randomized to receive a single oral dose of ibuprofen 400 mg on Day 1. Participants were followed up to 17 days after the last dose of study drug. | 161 |
| Placebo Participants were randomized to receive a single oral dose of Placebo (matched to ibuprofen 400 mg with caffeine 100 mg fixed dose combination) on Day 1. Participants were followed up to 17 days after the last dose of study drug. | 52 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Participants Unable To Swallow Capsule | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Ibuprofen 400 mg | Ibuprofen 400 mg + Caffeine 100 mg |
|---|---|---|---|---|
| Age, Continuous | 19.1 years STANDARD_DEVIATION 2.95 | 18.9 years STANDARD_DEVIATION 2.93 | 19.1 years STANDARD_DEVIATION 2.88 | 19.3 years STANDARD_DEVIATION 3.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 53 Participants | 8 Participants | 26 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 321 Participants | 44 Participants | 135 Participants | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 8 Participants | 0 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 1 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 346 Participants | 51 Participants | 142 Participants | 153 Participants |
| Sex: Female, Male Female | 196 Participants | 27 Participants | 84 Participants | 85 Participants |
| Sex: Female, Male Male | 178 Participants | 25 Participants | 77 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 161 | 0 / 52 |
| other Total, other adverse events | 15 / 161 | 15 / 161 | 8 / 52 |
| serious Total, serious adverse events | 0 / 161 | 0 / 161 | 0 / 52 |
Outcome results
Primary
Time Weighted Sum of Pain Relief Rating (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen
SPRID 0-8: time-weighted sum of PRID scores from 0 to 8 hours. PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Numerical pain severity rating (NPSR) scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible SPRID 0-8 score range: -80 to 112, higher scores = more improvement in pain.
Time frame: From 0 to 8 hours post-dose on Day 1
Population: Full analysis set (FAS) population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen | 55.5 units on a scale | Standard Error 1.8 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen | 52.8 units on a scale | Standard Error 1.8 |
p-value: 0.30695% CI: [-2.46, 7.82]ANCOVA
Secondary
Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose
NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a single post-dose time point: -10 to 10, higher positive value = greater improvement in pain.
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 5.0 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 5.9 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 3.8 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 5.4 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 5.8 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.4 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 4.7 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 2.0 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 4.5 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 5.6 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 3.4 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 5.5 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.5 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 2.1 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 4.2 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 5.1 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 5.5 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 5.3 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 4.8 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 4.1 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 3.6 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 3.3 units on a scale | Standard Error 0.2 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 1.3 units on a scale | Standard Error 0.4 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 1.3 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 0.6 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.4 units on a scale | Standard Error 0.2 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 1.2 units on a scale | Standard Error 0.4 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 0.6 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 1.1 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 0.7 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 1.3 units on a scale | Standard Error 0.4 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 1.2 units on a scale | Standard Error 0.3 |
| Placebo | Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 0.6 units on a scale | Standard Error 0.3 |
Comparison: PID score at 0.25 hourp-value: 0.80895% CI: [-0.27, 0.21]ANCOVA
Comparison: PID score at 0.25 hourp-value: 0.80495% CI: [-0.3, 0.39]ANCOVA
Comparison: PID score at 0.25 hrp-value: 0.67695% CI: [-0.27, 0.42]ANCOVA
Comparison: PID score at 0.5 hourp-value: 0.65495% CI: [-0.55, 0.35]ANCOVA
Comparison: PID score at 0.5 hourp-value: <0.00195% CI: [0.81, 2.1]ANCOVA
Comparison: PID score at 0.5 hourp-value: <0.00195% CI: [0.91, 2.2]ANCOVA
Comparison: PID score at 1 hourp-value: 0.04595% CI: [0.01, 0.97]ANCOVA
Comparison: PID score at 1 hourp-value: <0.00195% CI: [3.41, 4.78]ANCOVA
Comparison: PID score at 1 hourp-value: <0.00195% CI: [2.92, 4.29]ANCOVA
Comparison: PID score at 1.5 hourp-value: 0.01595% CI: [0.11, 1.06]ANCOVA
Comparison: PID score at 1.5 hourp-value: <0.00195% CI: [4.35, 5.71]ANOVA
Comparison: PID score at 1.5 hourp-value: <0.00195% CI: [3.76, 5.12]ANCOVA
Comparison: PID score at 2 hourp-value: 0.06695% CI: [-0.03, 0.91]ANCOVA
Comparison: PID score at 2 hourp-value: <0.00195% CI: [4.54, 5.89]ANCOVA
Comparison: PID score at 2 hourp-value: <0.00195% CI: [4.1, 5.45]ANCOVA
Comparison: PID score at 3 hourp-value: 0.18695% CI: [-0.16, 0.81]ANCOVA
Comparison: PID score at 3 hourp-value: <0.00195% CI: [3.98, 5.35]ANCOVA
Comparison: PID score at 3 hourp-value: <0.00195% CI: [3.65, 5.03]ANCOVA
Comparison: PID score at 4 hourp-value: 0.7595% CI: [-0.43, 0.6]ANCOVA
Comparison: PID score at 4 hourp-value: <0.00195% CI: [3.4, 4.87]ANCOVA
Comparison: PID score at 4 hourp-value: <0.00195% CI: [3.32, 4.79]ANCOVA
Comparison: PID score at 5 hourp-value: 0.36195% CI: [-0.3, 0.81]ANCOVA
Comparison: PID score at 5 hourp-value: <0.00195% CI: [2.95, 4.53]ANCOVA
Comparison: PID score at 5 hourp-value: <0.00195% CI: [2.69, 4.27]ANCOVA
Comparison: PID score at 6 hourp-value: 0.19595% CI: [-0.2, 0.98]ANCOVA
Comparison: PID score at 6 hourp-value: <0.00195% CI: [2.44, 4.13]ANCOVA
Comparison: PID score at 6 hourp-value: <0.00195% CI: [2.06, 3.74]ANCOVA
Comparison: PID score at 7 hourp-value: 0.66995% CI: [-0.49, 0.76]ANCOVA
Comparison: PID score at 7 hourp-value: <0.00195% CI: [1.53, 3.31]ANCOVA
Comparison: PID score at 7 hourp-value: <0.00195% CI: [1.4, 3.18]ANCOVA
Comparison: PID score at 8 hourp-value: 0.58195% CI: [-0.46, 0.82]ANCOVA
Comparison: PID score at 8 hourp-value: <0.00195% CI: [1.18, 3]ANCOVA
Comparison: PID score at 8 hourp-value: <0.00195% CI: [1, 2.82]ANCOVA
Secondary
Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose
PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain.
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 2.7 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 2.5 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.4 units on a scale | Standard Error 0 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 3.0 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 2.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 2.9 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 1.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 2.3 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 1.3 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 2.6 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 2.0 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 2.6 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 2.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 2.5 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.4 units on a scale | Standard Error 0 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 1.2 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 2.3 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 2.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 2.7 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 2.2 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 2.0 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 1.8 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 0.9 units on a scale | Standard Error 0.2 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 0.8 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 0.6 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.3 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 0.8 units on a scale | Standard Error 0.2 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 0.8 units on a scale | Standard Error 0.2 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 0.5 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 0.5 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 0.9 units on a scale | Standard Error 0.2 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 0.7 units on a scale | Standard Error 0.1 |
| Placebo | Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 0.5 units on a scale | Standard Error 0.1 |
Comparison: PRR score at 0.25 hourp-value: 0.57594% CI: [-0.09, 0.16]ANCOVA
Comparison: PRR score at 0.25 hourp-value: 0.42695% CI: [-0.11, 0.25]ANCOVA
Comparison: PRR score at 8 hourp-value: <0.00195% CI: [0.5, 1.35]ANCOVA
Comparison: PRR score at 0.25 hourp-value: 0.68695% CI: [-0.14, 0.22]ANCOVA
Comparison: PRR score at 0.5 hourp-value: 0.54395% CI: [-0.15, 0.29]ANCOVA
Comparison: PRR score at 0.5 hourp-value: <0.00195% CI: [0.49, 1.12]ANCOVA
Comparison: PRR score at 0.5 hourp-value: <0.00195% CI: [0.42, 1.05]ANCOVA
Comparison: PRR score at 1 hourp-value: 0.03895% CI: [0.01, 0.46]ANCOVA
Comparison: PRR score at 1 hourp-value: <0.00195% CI: [1.69, 2.33]ANCOVA
Comparison: PRR score at 1 hourp-value: <0.00195% CI: [1.46, 2.09]ANCOVA
Comparison: PRR score at 1.5 hourp-value: 0.02495% CI: [0.03, 0.47]ANCOVA
Comparison: PRR score at 1.5 hourp-value: <0.00195% CI: [2.02, 2.64]ANCOVA
Comparison: PRR score at 1.5 hourp-value: <0.00195% CI: [1.77, 2.39]ANCOVA
Comparison: PRR score at 2 hourp-value: 0.10395% CI: [-0.04, 0.4]ANCOVA
Comparison: PRR score at 2 hourp-value: <0.00195% CI: [2.09, 2.71]ANCOVA
Comparison: PRR score at 2 hourp-value: <0.00195% CI: [1.91, 2.53]ANCOVA
Comparison: PRR score at 3 hourp-value: 0.44895% CI: [-0.13, 0.29]ANCOVA
Comparison: PRR score at 3 hourp-value: <0.00195% CI: [1.86, 2.47]ANCOVA
Comparison: PRR score at 3 hourp-value: <0.00195% CI: [1.78, 2.38]ANCOVA
Comparison: PRR score at 4 hourp-value: 0.99795% CI: [-0.23, 0.23]ANCOVA
Comparison: PRR score at 4 hourp-value: <0.00195% CI: [1.61, 2.28]ANCOVA
Comparison: PRR score at 4 hourp-value: <0.00195% CI: [1.61, 2.28]ANCOVA
Comparison: PRR score at 5 hourp-value: 0.65695% CI: [-0.19, 0.31]ANCOVA
Comparison: PRR score at 5 hourp-value: <0.00195% CI: [1.36, 2.09]ANCOVA
Comparison: PRR score at 5 hourp-value: <0.00195% CI: [1.31, 2.03]ANCOVA
Comparison: PRR score at 6 hourp-value: 0.42594% CI: [-0.16, 0.38]ANCOVA
Comparison: PRR score at 6 hourp-value: <0.00195% CI: [1.12, 1.9]ANCOVA
Comparison: PRR score at 6 hourp-value: <0.00195% CI: [1.01, 1.79]ANCOVA
Comparison: PRR score at 7 hourp-value: 0.84195% CI: [-0.32, 0.26]ANCOVA
Comparison: PRR score at 7 hourp-value: <0.00195% CI: [0.69, 1.52]ANCOVA
Comparison: PRR score at 7 hourp-value: <0.00195% CI: [0.72, 1.55]ANCOVA
Comparison: PRR score at 8 hourp-value: 0.9895% CI: [-0.3, 0.3]ANCOVA
Comparison: PRR score at 8 hourp-value: <0.00195% CI: [0.5, 1.36]ANCOVA
Secondary
Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose
PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. At a single post-dose time point overall possible range for PRID score: -10 to 14, higher scores = more improvement in pain.
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 7.6 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 8.5 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 8.1 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 8.9 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 5.7 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 8.7 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 3.3 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 5.2 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 6.9 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 7.2 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.8 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 7.7 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 5.6 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 5.0 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 3.3 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 6.5 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 8.3 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 8.3 units on a scale | Standard Error 0.2 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 8.0 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 7.3 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 6.4 units on a scale | Standard Error 0.3 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 7 hour | 2.2 units on a scale | Standard Error 0.6 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1 hour | 1.1 units on a scale | Standard Error 0.4 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 4 hour | 2.0 units on a scale | Standard Error 0.5 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 5 hour | 2.1 units on a scale | Standard Error 0.5 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.5 hour | 1.0 units on a scale | Standard Error 0.4 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 8 hour | 2.2 units on a scale | Standard Error 0.6 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 6 hour | 2.1 units on a scale | Standard Error 0.5 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 2 hour | 1.3 units on a scale | Standard Error 0.4 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 0.25 hour | 0.7 units on a scale | Standard Error 0.2 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 3 hour | 1.8 units on a scale | Standard Error 0.4 |
| Placebo | Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | 1.5 hour | 1.1 units on a scale | Standard Error 0.4 |
Comparison: PRID at 7 hourp-value: <0.00195% CI: [2.12, 4.71]ANCOVA
Comparison: PRID at 8 hourp-value: 0.69895% CI: [-0.74, 1.11]ANCOVA
Comparison: PRID at 8 hourp-value: <0.00195% CI: [1.69, 4.34]ANCOVA
Comparison: PRID at 8 hourp-value: <0.00195% CI: [1.51, 4.16]ANCOVA
Comparison: PRID at 0.25 hourp-value: 0.97595% CI: [-0.35, 0.36]ANCOVA
Comparison: PRID at 0.25 hourp-value: 0.65495% CI: [-0.4, 0.63]ANCOVA
Comparison: PRID at 0.25 hourp-value: 0.6795% CI: [-0.4, 0.62]ANCOVA
Comparison: PRID at 0.5 hourp-value: 0.91795% CI: [-0.7, 0.63]ANCOVA
Comparison: PRID at 0.5 hourp-value: <0.00195% CI: [1.31, 3.2]ANCOVA
Comparison: PRID at 0.5 hourp-value: <0.00195% CI: [1.35, 3.24]ANCOVA
Comparison: PRID at 1 hourp-value: 0.03995% CI: [0.04, 1.42]ANCOVA
Comparison: PRID at 1 hourp-value: <0.00195% CI: [5.12, 7.1]ANCOVA
Comparison: PRID at 1 hourp-value: <0.00195% CI: [4.39, 6.37]ANCOVA
Comparison: PRID at 1.5 hourp-value: 0.01595% CI: [0.16, 1.52]ANCOVA
Comparison: PRID at 1.5 hourp-value: <0.00195% CI: [6.39, 8.33]ANCOVA
Comparison: PRID at 1.5 hourp-value: <0.00195% CI: [5.55, 7.49]ANCOVA
Comparison: PRID at 2 hourp-value: 0.07195% CI: [-0.05, 1.3]ANCOVA
Comparison: PRID at 2 hourp-value: <0.00195% CI: [6.65, 8.58]ANCOVA
Comparison: PRID at 2 hourp-value: <0.00195% CI: [6.03, 7.96]ANCOVA
Comparison: PRID at 3 hourp-value: 0.24395% CI: [-0.28, 1.09]ANCOVA
Comparison: PRID at 3 hourp-value: <0.00195% CI: [5.85, 7.8]ANCOVA
Comparison: PRID at 3 hourp-value: <0.00195% CI: [5.44, 7.4]ANCOVA
Comparison: PRID at 4 hourp-value: 0.82395% CI: [-0.65, 0.82]ANCOVA
Comparison: PRID at 4 hourp-value: <0.00195% CI: [5.02, 7.14]ANCOVA
Comparison: PRID at 4 hourp-value: <0.00195% CI: [4.94, 7.05]ANCOVA
Comparison: PRID at 5 hourp-value: 0.43895% CI: [-0.48, 1.11]ANCOVA
Comparison: PRID at 5 hourp-value: <0.00195% CI: [4.33, 6.6]ANCOVA
Comparison: PRID at 5 hourp-value: <0.00195% CI: [4.01, 6.29]ANCOVA
Comparison: PRID at 6 hourp-value: 0.2595% CI: [-0.35, 1.35]ANCOVA
Comparison: PRID at 6 hourp-value: <0.00195% CI: [3.58, 6.02]ANCOVA
Comparison: PRID at 6 hourp-value: <0.00195% CI: [3.08, 5.52]ANCOVA
Comparison: PRID at 7 hourp-value: 0.81895% CI: [-0.8, 1.01]ANCOVA
Comparison: PRID at 7 hourp-value: <0.00195% CI: [2.23, 4.82]ANCOVA
Secondary
Time to Onset of Achieving Meaningful Relief
When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as meaningful relief at the moment when they first experienced meaningful relief, that is, when the relief from the pain was meaningful to them. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered).
Time frame: Up to 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time to Onset of Achieving Meaningful Relief | 46.60 minutes |
| Ibuprofen 400 mg | Time to Onset of Achieving Meaningful Relief | 52.25 minutes |
| Placebo | Time to Onset of Achieving Meaningful Relief | NA minutes |
p-value: 0.028Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
Secondary
Time to Onset of First Perceptible Relief
When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as first perceptible relief at the moment when they first began to feel any pain relieving effect. It was when they first felt a little/noticeable pain relief. It did not mean that they felt completely better (though they might), but when they first felt any difference in pain that they had at present. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered).
Time frame: Up to 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time to Onset of First Perceptible Relief | 25.80 minutes |
| Ibuprofen 400 mg | Time to Onset of First Perceptible Relief | 24.52 minutes |
| Placebo | Time to Onset of First Perceptible Relief | NA minutes |
p-value: 0.861Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
Secondary
Time to Treatment Failure
Treatment failure was defined as time to first dose of rescue medication or study discontinuation of the participants due to lack of efficacy.
Time frame: Up to 8 hours post dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time to Treatment Failure | NA minutes |
| Ibuprofen 400 mg | Time to Treatment Failure | NA minutes |
| Placebo | Time to Treatment Failure | 310.00 minutes |
p-value: 0.838Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
p-value: <0.001Gehan-Wilcoxon test
Secondary
Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8)
SPID 0-2, SPID 0-4, SPID 0-6, SPID 0-8: time-weighted sum of PID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: score range from 0 = no pain to 10 = worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible range: SPID 0-2 = -20 to 20; SPID 0-4 = -40 to 40; SPID 0-6 = -60 to 60; SPID 0-8 = -80 to 80. Higher SPID scores = more improvement in pain.
Time frame: From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-2 | 8.7 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-4 | 19.9 units on a scale | Standard Error 0.6 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-6 | 29.5 units on a scale | Standard Error 0.9 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-8 | 36.6 units on a scale | Standard Error 1.3 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-4 | 18.8 units on a scale | Standard Error 0.6 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-2 | 8.0 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-6 | 27.7 units on a scale | Standard Error 0.9 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-8 | 34.6 units on a scale | Standard Error 1.3 |
| Placebo | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-4 | 3.5 units on a scale | Standard Error 1 |
| Placebo | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-8 | 8.8 units on a scale | Standard Error 2.3 |
| Placebo | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-2 | 1.2 units on a scale | Standard Error 0.5 |
| Placebo | Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-6 | 6.1 units on a scale | Standard Error 1.6 |
Comparison: SPID 0-2p-value: 0.06695% CI: [-0.05, 1.5]ANCOVA
Comparison: SPID 0-2p-value: <0.00195% CI: [6.44, 8.66]ANCOVA
Comparison: SPID 0-2p-value: <0.00195% CI: [5.71, 7.93]ANCOVA
Comparison: SPID 0-4p-value: 0.16595% CI: [-0.47, 2.74]ANCOVA
Comparison: SPID 0-4p-value: <0.00195% CI: [14.05, 18.64]ANCOVA
Comparison: SPID 0-4p-value: <0.00195% CI: [12.91, 17.51]ANCOVA
Comparison: SPID 0-6p-value: 0.17295% CI: [-0.78, 4.34]ANCOVA
Comparison: SPID 0-6p-value: <0.00195% CI: [19.71, 27.03]ANCOVA
Comparison: SPID 0-6p-value: <0.00195% CI: [17.93, 25.25]ANCOVA
Comparison: SPID 0-8p-value: 0.24995% CI: [-1.47, 5.67]ANCOVA
Comparison: SPID 0-8p-value: <0.00195% CI: [22.78, 32.99]ANCOVA
Comparison: SPID 0-8p-value: <0.00195% CI: [20.68, 30.89]ANCOVA
Secondary
Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8)
SPRID 0-2, SPRID 0-4, SPRID 0-6, SPRID 0-8: time-weighted sum of PRID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours respectively. PRID at each post-dose time point = PID + PRR. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on 5-point scale: 0=none, 1=a little, 2=some, 3=a lot, 4=complete; higher scores=more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on 11-point scale: range from 0=no pain to 10=worst possible pain; higher scores=worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value=greater improvement. Score range for: SPRID 0-2= -20 to 28; SPRID 0-4= -40 to 56; SPRID 0-6= -60 to 84; SPRID 0-8= -80 to 112. Higher SPRID scores=more improvement in pain.
Time frame: From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-6 | 44.5 units on a scale | Standard Error 1.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-8 | 55.5 units on a scale | Standard Error 1.8 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-2 | 13.3 units on a scale | Standard Error 0.4 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-4 | 30.0 units on a scale | Standard Error 0.8 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-8 | 52.8 units on a scale | Standard Error 1.8 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-2 | 12.2 units on a scale | Standard Error 0.4 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-4 | 28.5 units on a scale | Standard Error 0.8 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-6 | 42.1 units on a scale | Standard Error 1.3 |
| Placebo | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-2 | 2.2 units on a scale | Standard Error 0.7 |
| Placebo | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-8 | 14.6 units on a scale | Standard Error 3.3 |
| Placebo | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-4 | 6.0 units on a scale | Standard Error 1.5 |
| Placebo | Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-6 | 10.2 units on a scale | Standard Error 2.3 |
Comparison: SPRID 0-2p-value: 0.05695% CI: [-0.03, 2.2]ANCOVA
Comparison: SPRID 0-2p-value: <0.00195% CI: [9.54, 12.73]ANCOVA
Comparison: SPRID 0-2p-value: <0.00195% CI: [8.45, 11.64]ANCOVA
Comparison: SPRID 0-4p-value: 0.17795% CI: [-0.72, 3.87]ANCOVA
Comparison: SPRID 0-4p-value: <0.00195% CI: [20.76, 27.32]ANCOVA
Comparison: SPRID 0-4p-value: <0.00195% CI: [19.18, 25.75]ANCOVA
Comparison: SPRID 0-6p-value: 0.20195% CI: [-1.28, 6.06]ANCOVA
Comparison: SPRID 0-6p-value: <0.00195% CI: [29.06, 39.55]ANCOVA
Comparison: SPRID 0-6p-value: <0.00195% CI: [26.67, 37.16]ANCOVA
Comparison: SPRID 0-8p-value: <0.00195% CI: [33.49, 48.2]ANCOVA
Comparison: SPRID 0-8p-value: <0.00195% CI: [30.81, 45.52]ANCOVA
Secondary
Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8)
TOTPAR 0-2, TOTPAR 0-4, TOTPAR 0-6, TOTPAR 0-8: time-weighted sum of PRR scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. PRR score: at each post-dose time point participants answered to the question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Overall possible range: TOTPAR 0-2 = 0 to 8; TOTPAR 0-4 = 0 to 16; TOTPAR 0-6 = 0 to 24; TOTPAR 0-8 = 0 to 32. Higher TOTPAR scores = more improvement in pain.
Time frame: From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Population: FAS population included all randomized participants who received study medication and provided a baseline assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-4 | 10.2 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-8 | 18.8 units on a scale | Standard Error 0.6 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-6 | 15.0 units on a scale | Standard Error 0.4 |
| Ibuprofen 400 mg + Caffeine 100 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-2 | 4.6 units on a scale | Standard Error 0.1 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-6 | 14.4 units on a scale | Standard Error 0.4 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-8 | 18.2 units on a scale | Standard Error 0.6 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-4 | 9.7 units on a scale | Standard Error 0.3 |
| Ibuprofen 400 mg | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-2 | 4.2 units on a scale | Standard Error 0.1 |
| Placebo | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-8 | 5.8 units on a scale | Standard Error 1 |
| Placebo | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-2 | 1.0 units on a scale | Standard Error 0.2 |
| Placebo | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-6 | 4.1 units on a scale | Standard Error 0.7 |
| Placebo | Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-4 | 2.5 units on a scale | Standard Error 0.5 |
Comparison: TOTPAR 0-2p-value: 0.04495% CI: [0.01, 0.71]ANCOVA
Comparison: TOTPAR 0-2p-value: <0.00195% CI: [3.09, 4.09]ANCOVA
Comparison: TOTPAR 0-2p-value: <0.00195% CI: [2.73, 3.73]ANCOVA
Comparison: TOTPAR 0-4p-value: 0.22495% CI: [-0.27, 1.15]ANCOVA
Comparison: TOTPAR 0-4p-value: <0.00195% CI: [6.68, 8.71]ANCOVA
Comparison: TOTPAR 0-4p-value: <0.00195% CI: [6.23, 8.27]ANCOVA
Comparison: TOTPAR 0-6p-value: 0.29395% CI: [-0.53, 1.75]ANCOVA
Comparison: TOTPAR 0-6p-value: <0.00195% CI: [9.3, 12.56]ANCOVA
Comparison: TOTPAR 0-6p-value: <0.00195% CI: [8.69, 11.95]ANCOVA
Comparison: TOTPAR 0-8p-value: 0.47695% CI: [-1.03, 2.19]ANCOVA
Comparison: TOTPAR 0-8p-value: <0.00195% CI: [10.66, 15.26]ANCOVA
Comparison: TOTPAR 0-8p-value: <0.00195% CI: [10.08, 14.68]ANCOVA
Other Pre-specified
Number of Participants Who Used Concomitant Medications, and Rescue Medications
Rescue medication: participants who did not experience adequate relief after the 1 hour (post study drug dose) evaluation were given tramadol hydrochloride 50 to 100 mg orally or codeine sulfate 15 to 60 mg orally, based on the discretion of the Investigator, as rescue medication. If needed, 2 additional doses of rescue medications based on the discretion of the Investigator at the study center was given. Total maximum dose of tramadol was 300 mg and of codeine sulfate was 180 mg. Concomitant medication: medication received by participant other than study medication and rescue medication.
Time frame: Day 1
Population: Safety analysis population included all participants who received the study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Concomitant Medications | 25 Participants |
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Rescue Medications | 29 Participants |
| Ibuprofen 400 mg | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Concomitant Medications | 39 Participants |
| Ibuprofen 400 mg | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Rescue Medications | 25 Participants |
| Placebo | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Concomitant Medications | 11 Participants |
| Placebo | Number of Participants Who Used Concomitant Medications, and Rescue Medications | Rescue Medications | 28 Participants |
Other Pre-specified
Number of Participants Who Used Medications Prior to This Study
In this outcome measure number of participants who were using any type of medications, prior to start of the study were reported.
Time frame: At Screening
Population: Safety analysis population included all participants who received the study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants Who Used Medications Prior to This Study | 161 Participants |
| Ibuprofen 400 mg | Number of Participants Who Used Medications Prior to This Study | 161 Participants |
| Placebo | Number of Participants Who Used Medications Prior to This Study | 52 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Vital Signs Abnormalities
Vital signs included: heart rate, blood pressure, respiratory rate, and temperature. Normal range for the vital signs were: systolic blood pressure 90 to 140 millimeter of mercury (mmHg), diastolic blood pressure 60 to 90 mmHg, heart rate 50 to 110 beats per minute, respiratory rate 12 to 22 breaths per minute, and oral temperature 97.0 to 99.6 Fahrenheit (F). Value for vital signs outside the normal range was consider as abnormal. Clinical significance of vital signs abnormalities was determined at the investigator's discretion.
Time frame: Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Population: Safety analysis population included all participants who received the study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Ibuprofen 400 mg | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs are classified according to severity in 3 categories as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function).
Time frame: Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Population: Safety analysis population included all participants who received the study medication. Here, Overall Number of Participants Analyzed were those participants who had at least 1 treatment emergent AEs.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Moderate | 12 Participants |
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Mild | 3 Participants |
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Severe | 0 Participants |
| Ibuprofen 400 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Moderate | 7 Participants |
| Ibuprofen 400 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Mild | 8 Participants |
| Ibuprofen 400 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Severe | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Mild | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Severe | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity | Moderate | 8 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs)
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. Relatedness of an AE to study drug was assessed by investigator.
Time frame: Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Population: Safety analysis population included all participants who received the study medication. Here, Overall Number of Participants Analyzed were those participants who had at least 1 treatment emergent AEs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibuprofen 400 mg + Caffeine 100 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs) | 1 Participants |
| Ibuprofen 400 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs) | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs) | 2 Participants |