Pain, Post-Operative Pain, Third Molar Extraction
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of multiple doses of Ibuprofen 600 mg Extended-Release Tablets in a study of dental pain following extraction of third molar teeth.
Detailed description
This is a single-center, multiple-dose, randomized, placebo-controlled, double-blinded, parallel group trial to evaluate the efficacy and safety of multiple doses of Ibuprofen 600 mg Extended-Release Tablets in a study of dental pain following extraction of third molar teeth. The surgery will consist of surgical extraction of 1-2 impacted third molars, of which one must be a mandibular impaction that is partially impacted in either tissue or bone. Subjects will be stratified according to baseline pain intensity, as rated on an 11-point pain intensity numerical rating scale (PI-NRS)and gender.
Interventions
DRUGIbuprofen 600 mg Extended-Release Tablets
Ibuprofen 600 mg Extended-Release Tablet: One 600 mg tablet taken orally every 12 hours or twice daily (BID). Each dose was administered with at least 6 ounces of water. Dose 1 was administered at hour 0, Dose 2 was administered at hour 12, Dose 3 was administered at hour 24 and Dose 4 was administered at hour 36.
DRUGPlacebo
Placebo: One matching placebo tablet was taken orally every 12 hours or twice daily (BID). Each dose was administered with at least 6 ounces of water. Dose 1 was administered at hour 0, Dose 2 was administered at hour 12, Dose 3 was administered at hour 24 and Dose 4 was administered at hour 36.
Sponsors
AAIPharma
Jean Brown Research
SCOLR Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females 16 to 45 years of age; * Outpatients scheduled to undergo surgical extraction of 1-2 impacted third molar(s), one of which must be a mandibular impaction that is partially impacted in either tissue or bone; * At least a score of 5 on the 11-point pain intensity numerical rating scale (PI-NRS) at baseline; * Use of only the following preoperative medication(s) / anesthetic(s): short-acting local anesthetic (e.g., mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide; * Reliable, cooperative, and adequate intelligence to record the requested information on the analgesic questionnaire form; * Subjects (or the parent or legal guardian of subjects under the age of 18 years) are required to read, comprehend, and sign the informed consent. Subjects requiring a parent or legal guardian to sign the informed consent will be required to sign an assent; * Examined by the attending dentist or physician and medically cleared to participate in the study; and, * In general good health and have no contraindications to any of the study meds.
Exclusion criteria
* Presence of a serious medical condition (e.g., poorly controlled hypertension, poorly controlled diabetes, significantly impaired cardiac, renal or hepatic function, hyper- or hypothyroidism); * Use of a prescription or nonprescription drug with which the administration of ibuprofen, celecoxib, any other non-steroidal anti-inflammatory drug (NSAID), or acetaminophen, is contraindicated; * Acute local infection at the time of surgery that could confound the post-surgical evaluation; * Females who are pregnant, lactating, of child-bearing potential, or postmenopausal for less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a urine-based pregnancy test; * Presence or history (within 2 years of enrollment) of bleeding disorder(s) or peptic ulcer disease; * Presence or history (within the past year) of alcoholism or substance abuse. Subjects who are taking CNS or other psychotropic drugs (including St. John's Wort, or any other nutritional supplement known to have psychotropic effects) may be enrolled if they have been on stable doses of medication for at least 2 months, will maintain this dose throughout the study, and their condition is judged by the Principal Investigator to be well-controlled; * Habituation to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week); * History of allergic reaction (eg, asthma, rhinitis, swelling, shock, or hives) to ibuprofen, naproxen, aspirin, celecoxib, any other NSAID, or acetaminophen; * Prior use of any type of analgesic or NSAID 5 half-lives of that drug or less before taking the first dose of study medication, except for pre-anesthetic medication and anesthesia for the procedure; * Ingestion of any caffeine-containing beverages, chocolate, or alcohol 4 hours or less before taking the first dose of study medication; * Has taken an investigational product within the past 30 days; * Has previously been entered into this study; and, * The subject is a member of the study site staff either directly involved with the study, an employee of the Sponsor, or a relative of study site personnel directly involved with the study or Sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analgesic Efficacy, as Measured by the Sum of Pain Intensity Differences (SPID) Scale | from baseline to 12 hours after dose 1 | Analgesic efficacy for the 8-12 hour measurement interval after dose 1 using Sum of Pain Intensity Differences (SPID). An 11-point Pain Intensity Numerical Rating Scale (PI-NRS) was used to record pain intensity at baseline and 8, 9, 10, 11, 12 hours after dose 1. The scale went from 0 (no pain) to 10 (Worst possible pain). The outcome measure is based a mean of the sum of each of the five time points evaluated. The total time scale ranges from 0 to 50. Subjects were asked to select the number that best describes how much pain they had at the time of observation. |
| Durability of Effect as Measured by the Number of Subjects Achieving Meaningful Improvement in Pain Intensity Difference (PID) From Baseline at All Three Assessment Periods of 24, 36, and 48 Hours | 24, 36, and 48 hours | Response rate measured the durability of effect and was measured by the number of subjects achieving a reduction of at least 2 points (greater than or equal to 20%) from baseline on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) at all 3 assessment periods of 24, 36 and 48 hours. The scale went from 0 (no pain) to 10 (Worst possible pain). Subjects were asked to select the number that best describes how much pain they had at the time of observation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) of Subjects With Confirmed First Perceptible Relief Within 1 Hour of Dose 1 | Within 1 hour of Dose 1 | Percentage (percentage of total) of subjects with first perceptible relief within 1 hour of Dose 1. The assigned censored time for No Pain Relief was 240 minutes. |
| Percentage of Subjects Achieving Meaningful Relief as Indicated by the Time Recorded on the Second Stopwatch Following First Perceptible Relief | Within 4 hours post Dose 1 | Percentage(%) of subjects with confirmed first perceptible relief and meaningful relief after dose 1. Subjects that achieved both first perceptible relief and meaningful relief within the time allotted. The assigned censored time for No Pain Relief is 240 minutes. Meaningful relief is a subjective definition, based on each subject's determination of pain |
| Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | 0-12 hours after Dose 1 | The Pain Intensity Difference (PID) at each time point was derived by subtracting the pain intensity from baseline pain intensity, so that a higher value was indicative of a greater improvement. Time weighted SPID for each specified interval (scale ranges from 0 to 10; 0=no pain relief and 10= complete pain relief) was derived by first multiplying each PID score by the time from the previous time point, and adding them together for each scheduled time point within the time interval (e.g., 4-12 hours in case of SPID 4-12). Time weighted TOTPAR for each specified interval was similarly derived. |
| Duration of Relief After Dose 1 | Time to rescue or time of Dose 2 (up to 12 hours following dose 1) | Duration of relief was defined as the time to treatment failure (i.e.,taking rescue medication, or withdrawing due to lack of efficacy) up to the 12-hour time point. For those withdrawing from the study due to lack of efficacy prior to taking dose 2 or rescue medication, time to treatment failure was the time from dose 1 to the last assesment time. For those discontinuing from the study for any other reason, the time to treatment failure was censored at the last assessment time. |
| Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | 0-12 hours after taking Dose 1 | Percentage of participants who require rescue medication (Lortab) at or prior to hour 8, hour 10 and hour 12 were reported and 95% confidence intervals for the corresponding parameters were calculated. |
| Time to Confirmed First Perceptible Relief | Within 4 hours post Dose 1 | When the subject was administered study medication at Time 0, the Study Coordinator started 2 stopwatches. In an effort to determine the exact moment that the subject began to obtain noticeable pain relief, the subject was instructed to stop the stopwatch when initial relief was observed and again when meaningful relief was achieved. Time to confirmed first perceptible relief was defined as the time to first perceptible relief, provided that the subject also later stopped the second stopwatch indicating meaningful relief. The assigned censored time for No Pain Relief is 240 minutes. |
| Global Evaluation for Dose 1 | At 12 hours after Dose 1 or at time of rescue | Global evaluation for dose 1, either at the time of rescue or at dose 2 (hour 12), whichever came first were summarized. At the 12-hour time point but before Dose 2, or within 1 minute of rescue medication use (if it occurred before hour 12), the subject was to provide a Global Evaluation of Dose 1 of study medication on an 11 point PI-NRS in response to the following command: Select the number that best describes how you would rate this medication as a pain-reliever (select one number only). The range went from 0 (Very poor) to 10 (Excellent). |
| Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | At 24 hours or at time of rescue between 12 and 24 hours | Global evaluation, maximum relief, and overall relief scores for dose 2 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 2 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief). |
| Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | At 36 hours or at time rescue between 24 and 36 hours | Global evaluation, maximum relief, and overall relief scores for dose 3 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 3 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief). |
| Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | At 48 hours or at time of rescue between 36 and 48 hours. | Global evaluation, maximum relief, and overall relief scores for dose 4 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 4 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief). |
| Pain Relief and PID Scores at Individual Time Points for Dose 1 | 24, 36, 48 hours after taking Dose 1 | Pain relief and pain intensity difference (PID) scores at individual time points were summarized by descriptive statistics. The PID at each time point prior to dose 2 was derived by subtracting the pain intensity from the baseline pain intensity, so that a higher value was indicative of a greater improvement. Range of possible scores could be from 0 (no improvement) to 5 (greatest possible improvement) |
| Time to Confirmed Meaningful Relief | Within 4 hours post Dose 1 | When the subject was administered study medication at Time 0, the Study Coordinator started 2 stopwatches. To determine the exact moment that the subject began to notice pain relief, the subject was instructed to stop the stopwatch when initial relief was observed and again when meaningful relief was achieved. Time to confirmed meaningful relief was achieved if both stopwatches were stopped within the 4 hour observation period, when both initial and meaningful relief were observed. Meaningful relief is a subjective definition, based on each subjects determination of pain. |
Countries
United States
Participant flow
Recruitment details
Date First Subject Enrolled: 24 June 2008 Date Last Subject Enrolled: 11 October 2008 All subjects were to receive 4 doses of study drug or placebo at 12-hour intervals. Of the 12 subjects who prematurely discontinued study drug, 6 subjects received 1 dose of study drug, 2 subjects received 2 doses, and 4 subjects received 3 doses.
Participants by arm
| Arm | Count |
|---|---|
| Ibuprofen 600mg ER Participants received 600 mg 12-hour extended-release tablets twice daily (BID). | 169 |
| Placebo Participants received placebo tablet twice daily (BID) | 87 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Dosed incorrectly | 0 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | Placebo | Ibuprofen 600mg ER | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 35 Participants | 64 Participants | 99 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 105 Participants | 157 Participants |
| Age Continuous | 18.8 years STANDARD_DEVIATION 3.25 | 18.9 years STANDARD_DEVIATION 3.22 | 18.9 years STANDARD_DEVIATION 3.22 |
| Region of Enrollment United States | 87 participants | 169 participants | 256 participants |
| Sex: Female, Male Female | 47 Participants | 95 Participants | 142 Participants |
| Sex: Female, Male Male | 40 Participants | 74 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 169 | 0 / 87 |
| serious Total, serious adverse events | 0 / 169 | 0 / 87 |
Outcome results
Primary
Analgesic Efficacy, as Measured by the Sum of Pain Intensity Differences (SPID) Scale
Analgesic efficacy for the 8-12 hour measurement interval after dose 1 using Sum of Pain Intensity Differences (SPID). An 11-point Pain Intensity Numerical Rating Scale (PI-NRS) was used to record pain intensity at baseline and 8, 9, 10, 11, 12 hours after dose 1. The scale went from 0 (no pain) to 10 (Worst possible pain). The outcome measure is based a mean of the sum of each of the five time points evaluated. The total time scale ranges from 0 to 50. Subjects were asked to select the number that best describes how much pain they had at the time of observation.
Time frame: from baseline to 12 hours after dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen 600mg ER | Analgesic Efficacy, as Measured by the Sum of Pain Intensity Differences (SPID) Scale | 14.80 Units on a scale | Standard Deviation 16.331 |
| Placebo | Analgesic Efficacy, as Measured by the Sum of Pain Intensity Differences (SPID) Scale | 0.40 Units on a scale | Standard Deviation 11.933 |
Comparison: The null versus alternative hypothesis regarding the analgesic efficacy using the SPID 8-12 was compared between the 2 treatment groups using an analysis of covariance (ANCOVA)model with each subject's outcome being his/her SPID 8-12 as the dependent variable in the ANCOVA model with terms for gender, treatment, and baseline pain score categories (stratified as ≤7 and \>7).p-value: <0.0001ANCOVA
Primary
Durability of Effect as Measured by the Number of Subjects Achieving Meaningful Improvement in Pain Intensity Difference (PID) From Baseline at All Three Assessment Periods of 24, 36, and 48 Hours
Response rate measured the durability of effect and was measured by the number of subjects achieving a reduction of at least 2 points (greater than or equal to 20%) from baseline on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) at all 3 assessment periods of 24, 36 and 48 hours. The scale went from 0 (no pain) to 10 (Worst possible pain). Subjects were asked to select the number that best describes how much pain they had at the time of observation.
Time frame: 24, 36, and 48 hours
Population: Intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibuprofen 600mg ER | Durability of Effect as Measured by the Number of Subjects Achieving Meaningful Improvement in Pain Intensity Difference (PID) From Baseline at All Three Assessment Periods of 24, 36, and 48 Hours | 123 participants |
| Placebo | Durability of Effect as Measured by the Number of Subjects Achieving Meaningful Improvement in Pain Intensity Difference (PID) From Baseline at All Three Assessment Periods of 24, 36, and 48 Hours | 47 participants |
Comparison: The null versus alternative hypothesis regarding the durability of analgesic efficacy using the PID scores at 24, 36, and 48 hours.An individual subject was to achieve the 2-point reduction at all 3 terminal time points in order to be defined as responder.p-value: <0.0017ANCOVA
Secondary
Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID)
The Pain Intensity Difference (PID) at each time point was derived by subtracting the pain intensity from baseline pain intensity, so that a higher value was indicative of a greater improvement. Time weighted SPID for each specified interval (scale ranges from 0 to 10; 0=no pain relief and 10= complete pain relief) was derived by first multiplying each PID score by the time from the previous time point, and adding them together for each scheduled time point within the time interval (e.g., 4-12 hours in case of SPID 4-12). Time weighted TOTPAR for each specified interval was similarly derived.
Time frame: 0-12 hours after Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 0-12 hours | 54.59 Time weighted units on a scale | Standard Deviation 40.83 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 0-4 hours | 16.84 Time weighted units on a scale | Standard Deviation 11.854 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 4-8 hours | 25.94 Time weighted units on a scale | Standard Deviation 19.013 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 4-12 hours | 43.38 Time weighted units on a scale | Standard Deviation 33.851 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 0-12 hours | 37.20 Time weighted units on a scale | Standard Deviation 34.791 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 0-4 hours | 11.64 Time weighted units on a scale | Standard Deviation 10.222 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 4-8 hours | 17.88 Time weighted units on a scale | Standard Deviation 16.158 |
| Ibuprofen 600mg ER | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 4-12 hours | 29.49 Time weighted units on a scale | Standard Deviation 28.654 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 4-12 hours | 0.67 Time weighted units on a scale | Standard Deviation 20.617 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 0-12 hours | 12.05 Time weighted units on a scale | Standard Deviation 27.114 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 0-12 hours | 0.45 Time weighted units on a scale | Standard Deviation 24.378 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 0-4 hours | 3.18 Time weighted units on a scale | Standard Deviation 6.749 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 4-8 hours | 0.24 Time weighted units on a scale | Standard Deviation 11.034 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 4-8 hours | 5.34 Time weighted units on a scale | Standard Deviation 12.393 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | SPID 0-4 hours | -0.18 Time weighted units on a scale | Standard Deviation 6.591 |
| Placebo | Analgesic Efficacy for the 0-12, 0-4, 4-8, and 4-12 Hour Dosing Intervals After Dose 1 Using Total Pain Relief (TOTPAR) and Sum of Pain Intensity Difference(SPID) | TOTPAR 4-12 hours | 9.92 Time weighted units on a scale | Standard Deviation 23.411 |
Comparison: The PID at each time point prior to dose 2 was derived by substracting the pain intensity from the base line pain intensity, so that a higher value was indicative of a greater improvement. Time weighted SPID for each specified interval was derived by first multiplying each PID score by the time from the previous time point, and adding them together for each scheduled time point within the time interval. Time weighted TOTPAR for ech specified interval was similarly derived.p-value: <0.0001ANCOVA
Secondary
Duration of Relief After Dose 1
Duration of relief was defined as the time to treatment failure (i.e.,taking rescue medication, or withdrawing due to lack of efficacy) up to the 12-hour time point. For those withdrawing from the study due to lack of efficacy prior to taking dose 2 or rescue medication, time to treatment failure was the time from dose 1 to the last assesment time. For those discontinuing from the study for any other reason, the time to treatment failure was censored at the last assessment time.
Time frame: Time to rescue or time of Dose 2 (up to 12 hours following dose 1)
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 600mg ER | Duration of Relief After Dose 1 | 720 Minutes |
| Placebo | Duration of Relief After Dose 1 | 101 Minutes |
p-value: <0.0001Log Rank
Secondary
Global Evaluation for Dose 1
Global evaluation for dose 1, either at the time of rescue or at dose 2 (hour 12), whichever came first were summarized. At the 12-hour time point but before Dose 2, or within 1 minute of rescue medication use (if it occurred before hour 12), the subject was to provide a Global Evaluation of Dose 1 of study medication on an 11 point PI-NRS in response to the following command: Select the number that best describes how you would rate this medication as a pain-reliever (select one number only). The range went from 0 (Very poor) to 10 (Excellent).
Time frame: At 12 hours after Dose 1 or at time of rescue
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen 600mg ER | Global Evaluation for Dose 1 | 6.05 Units on a scale | Standard Deviation 3.536 |
| Placebo | Global Evaluation for Dose 1 | 1.79 Units on a scale | Standard Deviation 2.898 |
Comparison: Global evaluation for dose 1, either at the time of rescue or at dose 2 whichever came first were summarized by descriptive statistics based on non-missing data. The range went from 0 (Very poor) to 10 (Excellent) units on an 11-point Pain Intensity Numerical Rating Scale (PI-NRS).p-value: <0.0001ANCOVA
Secondary
Global Evaluation, Maximum Relief, and Overall Relief for Dose 2
Global evaluation, maximum relief, and overall relief scores for dose 2 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 2 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief).
Time frame: At 24 hours or at time of rescue between 12 and 24 hours
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Global Evalution for Dose 2 | 6.82 Units on a scale | Standard Deviation 2.914 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Maximum Relief for Dose 2 | 7.27 Units on a scale | Standard Deviation 2.997 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Overall Relief for Dose 2 | 6.62 Units on a scale | Standard Deviation 3.005 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Global Evalution for Dose 2 | 4.24 Units on a scale | Standard Deviation 3.673 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Maximum Relief for Dose 2 | 5.02 Units on a scale | Standard Deviation 3.864 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 2 | Overall Relief for Dose 2 | 4.46 Units on a scale | Standard Deviation 3.588 |
Comparison: Global evaluation scores for dose 2 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics.~The subjects were to provide global evaluation of dose 2 study medication using a range that went from 0 (Very poor) to 10 (Excellent) units on an 11-point Pain Intensity Numerical Rating Scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Maximum relief scores for dose 2 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics.~The subjects were to provide maximum relief scores for dose 2 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Overall relief scores for dose 2 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics.~The subjects were to provide overall relief scores for dose 2 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Secondary
Global Evaluation, Maximum Relief, and Overall Relief for Dose 3
Global evaluation, maximum relief, and overall relief scores for dose 3 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 3 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief).
Time frame: At 36 hours or at time rescue between 24 and 36 hours
Population: Intention to Treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Global Evaluation for Dose 3 | 7.14 Units on a scale | Standard Deviation 2.839 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Maximum Relief for Dose 3 | 7.61 Units on a scale | Standard Deviation 2.922 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Overall Relief for Dose 3 | 6.76 Units on a scale | Standard Deviation 2.942 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Global Evaluation for Dose 3 | 4.98 Units on a scale | Standard Deviation 3.549 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Maximum Relief for Dose 3 | 5.63 Units on a scale | Standard Deviation 3.805 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 3 | Overall Relief for Dose 3 | 5.02 Units on a scale | Standard Deviation 3.634 |
Comparison: Global evaluation scores for dose 3 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide global evaluation of dose 3 study medication using a range that went from 0 (Very poor) to 10 (Excellent) units on an 11-point Pain Intensity Numerical Rating Scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Maximum relief scores for dose 3 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide maximum relief of dose 3 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Overall relief scores for dose 3 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide overall relief of dose 3 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Secondary
Global Evaluation, Maximum Relief, and Overall Relief for Dose 4
Global evaluation, maximum relief, and overall relief scores for dose 4 were summarized with descriptive statistics. The subject was to provide a description for the Global Evaluation, maximum relief and overall relief of Dose 4 of study medication on an 11 point PI-NRS: Global Evaluation: rate the study medication as a pain-reliever; Maximum Pain Relief: maximum pain relief received from the last dose; Overall Pain Relief: overall quantity of pain relief received from the last dose. The range went from 0 (Very poor or No relief) to 10 (Excellent or Complete relief).
Time frame: At 48 hours or at time of rescue between 36 and 48 hours.
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Overall Relief for Dose 4 | 7.06 Units on a scale | Standard Deviation 3.045 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Global Evalution for Dose 4 | 7.26 Units on a scale | Standard Deviation 2.953 |
| Ibuprofen 600mg ER | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Maximum Relief for Dose 4 | 7.66 Units on a scale | Standard Deviation 2.97 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Global Evalution for Dose 4 | 4.70 Units on a scale | Standard Deviation 3.715 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Maximum Relief for Dose 4 | 5.34 Units on a scale | Standard Deviation 3.97 |
| Placebo | Global Evaluation, Maximum Relief, and Overall Relief for Dose 4 | Overall Relief for Dose 4 | 4.89 Units on a scale | Standard Deviation 3.803 |
Comparison: Global evaluation scores for dose 4 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide global evaluation of dose 4 study medication using a range that went from 0 (Very poor) to 10 (Excellent) units on an 11-point Pain Intensity Numerical Rating Scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Maximum relief scores for dose 4 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide maximum relief of dose 4 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Comparison: Overall relief scores for dose 4 were summarized by descriptive statistics. Only non-missing values are used for the summary statistics. The subjects were to provide overall relief of dose 4 study medication on an 11-point pain intensity numerical rating scale (PI-NRS)in response to pain relief.p-value: <0.0001ANCOVA
Secondary
Pain Relief and PID Scores at Individual Time Points for Dose 1
Pain relief and pain intensity difference (PID) scores at individual time points were summarized by descriptive statistics. The PID at each time point prior to dose 2 was derived by subtracting the pain intensity from the baseline pain intensity, so that a higher value was indicative of a greater improvement. Range of possible scores could be from 0 (no improvement) to 5 (greatest possible improvement)
Time frame: 24, 36, 48 hours after taking Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 600mg ER | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 24 hours after dose 1. | 3.11 Units on a scale | Standard Deviation 3.466 |
| Ibuprofen 600mg ER | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 36 hours after dose 1. | 3.10 Units on a scale | Standard Deviation 3.46 |
| Ibuprofen 600mg ER | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 48 hours after dose 1. | 3.44 Units on a scale | Standard Deviation 3.756 |
| Placebo | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 24 hours after dose 1. | 0.18 Units on a scale | Standard Deviation 2.599 |
| Placebo | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 36 hours after dose 1. | 0.22 Units on a scale | Standard Deviation 2.704 |
| Placebo | Pain Relief and PID Scores at Individual Time Points for Dose 1 | 48 hours after dose 1. | 0.22 Units on a scale | Standard Deviation 2.721 |
Comparison: The pain relief and PID scores at individual time points were summarized by descriptive statistics. The test and reference were compared at each individual time point at 24, 36 and 48 hours.p-value: <0.0001ANCOVA
Secondary
Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1
Percentage of participants who require rescue medication (Lortab) at or prior to hour 8, hour 10 and hour 12 were reported and 95% confidence intervals for the corresponding parameters were calculated.
Time frame: 0-12 hours after taking Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Ibuprofen 600mg ER | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 8 hours after dose 1 | 31.4 Percentage of participants |
| Ibuprofen 600mg ER | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 10 hours after dose 1 | 34.9 Percentage of participants |
| Ibuprofen 600mg ER | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 12 hours after dose 1 | 36.1 Percentage of participants |
| Placebo | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 8 hours after dose 1 | 82.8 Percentage of participants |
| Placebo | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 10 hours after dose 1 | 85.1 Percentage of participants |
| Placebo | Percentage of Participants Who Require Rescue Medication at or Prior to Hour 8, Hour 10, and Hour 12 After Taking Dose 1 | Rescue at or prior to 12 hours after dose 1 | 85.1 Percentage of participants |
Comparison: The proportions of subjects who rescued at or prior to hour 8, hour 10, and hour 12 were reported and 95% confidence intervals for the corresponding parameters were calculated.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving Meaningful Relief as Indicated by the Time Recorded on the Second Stopwatch Following First Perceptible Relief
Percentage(%) of subjects with confirmed first perceptible relief and meaningful relief after dose 1. Subjects that achieved both first perceptible relief and meaningful relief within the time allotted. The assigned censored time for No Pain Relief is 240 minutes. Meaningful relief is a subjective definition, based on each subject's determination of pain
Time frame: Within 4 hours post Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibuprofen 600mg ER | Percentage of Subjects Achieving Meaningful Relief as Indicated by the Time Recorded on the Second Stopwatch Following First Perceptible Relief | 69 Percent of participants |
| Placebo | Percentage of Subjects Achieving Meaningful Relief as Indicated by the Time Recorded on the Second Stopwatch Following First Perceptible Relief | 17 Percent of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage (%) of Subjects With Confirmed First Perceptible Relief Within 1 Hour of Dose 1
Percentage (percentage of total) of subjects with first perceptible relief within 1 hour of Dose 1. The assigned censored time for No Pain Relief was 240 minutes.
Time frame: Within 1 hour of Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibuprofen 600mg ER | Percentage (%) of Subjects With Confirmed First Perceptible Relief Within 1 Hour of Dose 1 | 62 Percent of participants |
| Placebo | Percentage (%) of Subjects With Confirmed First Perceptible Relief Within 1 Hour of Dose 1 | 12 Percent of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Time to Confirmed First Perceptible Relief
When the subject was administered study medication at Time 0, the Study Coordinator started 2 stopwatches. In an effort to determine the exact moment that the subject began to obtain noticeable pain relief, the subject was instructed to stop the stopwatch when initial relief was observed and again when meaningful relief was achieved. Time to confirmed first perceptible relief was defined as the time to first perceptible relief, provided that the subject also later stopped the second stopwatch indicating meaningful relief. The assigned censored time for No Pain Relief is 240 minutes.
Time frame: Within 4 hours post Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 600mg ER | Time to Confirmed First Perceptible Relief | 42.00 Minutes |
| Placebo | Time to Confirmed First Perceptible Relief | 240 Minutes |
Comparison: Time to confirmed first perceptible relief was defined as the time to first perceptible relief, provided that the subject also stopped the second stopwatch indicating meaningful relief. For those who failed to achieve confirmed first perceptible and/or meaningful relief, a censored time was assigned.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Time to Confirmed Meaningful Relief
When the subject was administered study medication at Time 0, the Study Coordinator started 2 stopwatches. To determine the exact moment that the subject began to notice pain relief, the subject was instructed to stop the stopwatch when initial relief was observed and again when meaningful relief was achieved. Time to confirmed meaningful relief was achieved if both stopwatches were stopped within the 4 hour observation period, when both initial and meaningful relief were observed. Meaningful relief is a subjective definition, based on each subjects determination of pain.
Time frame: Within 4 hours post Dose 1
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen 600mg ER | Time to Confirmed Meaningful Relief | 108 Minutes |
| Placebo | Time to Confirmed Meaningful Relief | 240 Minutes |
Comparison: Time to confirmed first perceptible relief was defined as the time to first perceptible relief, provided that the subject also stopped the second stopwatch indicating meaningful relief. For those who failed to achieve confirmed first perceptible and/or meaningful relief, a censored time was assigned.p-value: <0.0001Cochran-Mantel-Haenszel