Trial Outcomes & Findings for Ibuprofen Extended-Release Dental Pain Study (NCT NCT00707057)
NCT ID: NCT00707057
Last Updated: 2011-03-24
Results Overview
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.
COMPLETED
PHASE3
256 participants
from baseline to 12 hours after dose 1
2011-03-24
Participant Flow
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.
Participant milestones
| Measure |
Ibuprofen 600mg ER
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Overall Study
STARTED
|
169
|
87
|
|
Overall Study
COMPLETED
|
161
|
83
|
|
Overall Study
NOT COMPLETED
|
8
|
4
|
Reasons for withdrawal
| Measure |
Ibuprofen 600mg ER
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
8
|
3
|
|
Overall Study
Dosed incorrectly
|
0
|
1
|
Baseline Characteristics
Ibuprofen Extended-Release Dental Pain Study
Baseline characteristics by cohort
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
Total
n=256 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
64 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
105 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
157 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
18.9 years
STANDARD_DEVIATION 3.22 • n=5 Participants
|
18.8 years
STANDARD_DEVIATION 3.25 • n=7 Participants
|
18.9 years
STANDARD_DEVIATION 3.22 • n=5 Participants
|
|
Sex: Female, Male
Female
|
95 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
169 participants
n=5 Participants
|
87 participants
n=7 Participants
|
256 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: from baseline to 12 hours after dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Analgesic Efficacy, as Measured by the Sum of Pain Intensity Differences (SPID) Scale
|
14.80 Units on a scale
Standard Deviation 16.331 • Interval 0.65 to 0.78
|
0.40 Units on a scale
Standard Deviation 11.933 • Interval 0.23 to 0.43
|
PRIMARY outcome
Timeframe: 24, 36, and 48 hoursPopulation: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
47 participants
|
SECONDARY outcome
Timeframe: Within 4 hours post Dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Time to Confirmed "First Perceptible" Relief
|
42.00 Minutes
Interval 4.0 to 81.0
|
240 Minutes
Interval 240.0 to 240.0
|
SECONDARY outcome
Timeframe: Within 4 hours post Dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Time to Confirmed "Meaningful" Relief
|
108 Minutes
Interval 18.0 to 240.0
|
240 Minutes
Interval 240.0 to 240.0
|
SECONDARY outcome
Timeframe: Within 1 hour of Dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Percentage (%) of Subjects With Confirmed First Perceptible Relief Within 1 Hour of Dose 1
|
62 Percent of participants
Interval 54.0 to 69.0
|
12 Percent of participants
Interval 5.0 to 18.0
|
SECONDARY outcome
Timeframe: Within 4 hours post Dose 1Population: Intention to treat (ITT)
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
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Percentage of Subjects Achieving "Meaningful" Relief as Indicated by the Time Recorded on the Second Stopwatch Following "First Perceptible" Relief
|
69 Percent of participants
Interval 62.0 to 76.0
|
17 Percent of participants
Interval 9.0 to 25.0
|
SECONDARY outcome
Timeframe: 0-12 hours after Dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
9.92 Time weighted units on a scale
Standard Deviation 23.411
|
|
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
|
0.45 Time weighted units on a scale
Standard Deviation 24.378
|
|
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 40.830
|
12.05 Time weighted units on a scale
Standard Deviation 27.114
|
|
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
|
3.18 Time weighted units on a scale
Standard Deviation 6.749
|
|
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
|
5.34 Time weighted units on a scale
Standard Deviation 12.393
|
|
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
|
-0.18 Time weighted units on a scale
Standard Deviation 6.591
|
|
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
|
0.24 Time weighted units on a scale
Standard Deviation 11.034
|
|
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
|
0.67 Time weighted units on a scale
Standard Deviation 20.617
|
SECONDARY outcome
Timeframe: Time to rescue or time of Dose 2 (up to 12 hours following dose 1)Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Duration of Relief After Dose 1
|
720 Minutes
Interval 1.0 to 720.0
|
101 Minutes
Interval 1.0 to 720.0
|
SECONDARY outcome
Timeframe: 0-12 hours after taking Dose 1Population: Intention to treat (ITT)
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.
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
Interval 24.0 to 38.0
|
82.8 Percentage of participants
Interval 75.0 to 91.0
|
|
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
Interval 28.0 to 42.0
|
85.1 Percentage of participants
Interval 78.0 to 93.0
|
|
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
Interval 29.0 to 43.0
|
85.1 Percentage of participants
Interval 78.0 to 93.0
|
SECONDARY outcome
Timeframe: 24, 36, 48 hours after taking Dose 1Population: Intention to treat (ITT)
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)
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
0.18 Units on a scale
Standard Deviation 2.599
|
|
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 3.460
|
0.22 Units on a scale
Standard Deviation 2.704
|
|
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
|
0.22 Units on a scale
Standard Deviation 2.721
|
SECONDARY outcome
Timeframe: At 12 hours after Dose 1 or at time of rescuePopulation: Intention to treat (ITT)
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).
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
Global Evaluation for Dose 1
|
6.05 Units on a scale
Standard Deviation 3.536
|
1.79 Units on a scale
Standard Deviation 2.898
|
SECONDARY outcome
Timeframe: At 24 hours or at time of rescue between 12 and 24 hoursPopulation: Intention to treat (ITT)
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).
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
4.46 Units on a scale
Standard Deviation 3.588
|
|
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
|
4.24 Units on a scale
Standard Deviation 3.673
|
|
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
|
5.02 Units on a scale
Standard Deviation 3.864
|
SECONDARY outcome
Timeframe: At 36 hours or at time rescue between 24 and 36 hoursPopulation: Intention to Treat (ITT)
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).
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
4.98 Units on a scale
Standard Deviation 3.549
|
|
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
|
5.63 Units on a scale
Standard Deviation 3.805
|
|
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
|
5.02 Units on a scale
Standard Deviation 3.634
|
SECONDARY outcome
Timeframe: At 48 hours or at time of rescue between 36 and 48 hours.Population: Intention to treat (ITT)
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).
Outcome measures
| Measure |
Ibuprofen 600mg ER
n=169 Participants
Participants received 600 mg 12-hour extended-release tablets twice daily (BID).
|
Placebo
n=87 Participants
Participants received placebo tablet twice daily (BID)
|
|---|---|---|
|
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
|
4.70 Units on a scale
Standard Deviation 3.715
|
|
Global Evaluation, Maximum Relief, and Overall Relief for Dose 4
Maximum Relief for Dose 4
|
7.66 Units on a scale
Standard Deviation 2.970
|
5.34 Units on a scale
Standard Deviation 3.970
|
|
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
|
4.89 Units on a scale
Standard Deviation 3.803
|
Adverse Events
Ibuprofen 600mg ER
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Stephen Turner, VP and Chief Technical Officer
SCOLR Pharma Inc
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60