Trial Outcomes & Findings for Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain (NCT NCT01929031)
NCT ID: NCT01929031
Last Updated: 2016-11-16
Results Overview
SPRID0-8h: Time-weighted sum of PAR and PID from 0 to 8 hours, score range: -40 (worst) to 112 (best). PI was assessed on a 0-10 numerical pain rating scale (NPRS), where 0=no pain and 10=worst possible pain, pre-dose and at 0.25,0.5,0.75,1,1.5,2,3,4,5, 6,7 and 8 hours; PAR was assessed on a 5-point verbal rating scale (VRS) (0=none to 4=complete) at the same post-dose time points. Time-weights were equal to the elapsed time (hour) between the time point of interest and the preceding time point. All PAR and pain intensity (PI) assessments completed after the patient had taken rescue medication or the second dose of study medication, whichever was first, until hour 8 were considered missing. Last observation carried forward (LOCF) was used with the last completed PI/PAR assessments prior to first rescue/second study medication, whichever was first, to impute missing values up to 8 hours.
COMPLETED
PHASE3
562 participants
0 to 8 hours
2016-11-16
Participant Flow
Participant milestones
| Measure |
Ibuprofen/Caffeine - Ibuprofen/Caffeine
Study stage 1: One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Ibuprofen - Ibuprofen
Study stage 1: One Ibuprofen 400mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
Caffeine - Ibuprofen/Caffeine
Study stage 1: One Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Caffeine - Ibuprofen
Study stage 1: One Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
Placebo - Ibuprofen/Caffeine
Study stage 1: One Placebo tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Placebo - Ibuprofen
Study stage 1: One Placebo tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
213
|
209
|
35
|
35
|
34
|
36
|
|
Overall Study
COMPLETED
|
209
|
207
|
34
|
35
|
33
|
35
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
1
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
Ibuprofen/Caffeine - Ibuprofen/Caffeine
Study stage 1: One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Ibuprofen - Ibuprofen
Study stage 1: One Ibuprofen 400mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
Caffeine - Ibuprofen/Caffeine
Study stage 1: One Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Caffeine - Ibuprofen
Study stage 1: One Caffeine 100mg tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
Placebo - Ibuprofen/Caffeine
Study stage 1: One Placebo tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg/Caffeine 100mg tablet, while awake, over 5 days
|
Placebo - Ibuprofen
Study stage 1: One Placebo tablet after dental surgery; Study stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400mg tablet, while awake, over 5 days
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Reason other than specified above
|
0
|
1
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain
Baseline characteristics by cohort
| Measure |
Placebo Stage 1
n=70 Participants
One Placebo tablet after dental surgery
|
Caffeine Stage 1
n=70 Participants
One Caffeine 100mg tablet after dental surgery
|
Ibuprofen Stage 1
n=209 Participants
One Ibuprofen 400mg tablet after dental surgery
|
Ibuprofen/Caffeine Stage 1
n=213 Participants
One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery
|
Total
n=562 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
19.3 years
STANDARD_DEVIATION 1.77 • n=99 Participants
|
19.2 years
STANDARD_DEVIATION 1.72 • n=107 Participants
|
19.6 years
STANDARD_DEVIATION 1.96 • n=206 Participants
|
19.5 years
STANDARD_DEVIATION 2.06 • n=7 Participants
|
19.5 years
STANDARD_DEVIATION 1.95 • n=31 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
142 Participants
n=206 Participants
|
131 Participants
n=7 Participants
|
358 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
82 Participants
n=7 Participants
|
204 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
70 participants
n=99 Participants
|
70 participants
n=107 Participants
|
209 participants
n=206 Participants
|
213 participants
n=7 Participants
|
562 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 0 to 8 hoursPopulation: Randomized patients who used at least one dose of study medication and provided any post-treatment data for the primary efficacy endpoint (FAS)
SPRID0-8h: Time-weighted sum of PAR and PID from 0 to 8 hours, score range: -40 (worst) to 112 (best). PI was assessed on a 0-10 numerical pain rating scale (NPRS), where 0=no pain and 10=worst possible pain, pre-dose and at 0.25,0.5,0.75,1,1.5,2,3,4,5, 6,7 and 8 hours; PAR was assessed on a 5-point verbal rating scale (VRS) (0=none to 4=complete) at the same post-dose time points. Time-weights were equal to the elapsed time (hour) between the time point of interest and the preceding time point. All PAR and pain intensity (PI) assessments completed after the patient had taken rescue medication or the second dose of study medication, whichever was first, until hour 8 were considered missing. Last observation carried forward (LOCF) was used with the last completed PI/PAR assessments prior to first rescue/second study medication, whichever was first, to impute missing values up to 8 hours.
Outcome measures
| Measure |
Placebo
n=70 Participants
One Placebo tablet after dental surgery
|
Caffeine
n=70 Participants
One Caffeine 100mg tablet after dental surgery
|
Ibuprofen
n=209 Participants
One Ibuprofen 400mg tablet after dental surgery
|
Ibuprofen/Caffeine
n=213 Participants
One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery
|
|---|---|---|---|---|
|
Time-weighted Sum of Pain Relief (PAR) and Pain Intensity Difference (PID) From 0 to 8 Hours (SPRID0-8h)
|
10.554 units on a scale
Standard Error 3.527
|
15.824 units on a scale
Standard Error 3.525
|
40.165 units on a scale
Standard Error 2.047
|
52.291 units on a scale
Standard Error 2.027
|
SECONDARY outcome
Timeframe: 0 to 2 hoursPopulation: Patients who used at least one dose of study medication and provided any post-treatment data for the primary efficacy endpoint (FAS)
SPRID0-2h: Time-weighted sum of PAR and PID from 0 to 2 hours, score range: -10 (worst) to 28 (best). PI was assessed on a 0-10 numerical pain rating scale (NPRS), where 0=no pain and 10=worst possible pain, pre-dose and at 0.25,0.5,0.75,1,1.5 and 2 hours; PAR was assessed on a 5-point verbal rating scale (VRS) (0=none to 4=complete) at the same post-dose time points. Time-weights were equal to the elapsed time (hour) between the time point of interest and the preceding time point. All PAR and pain intensity (PI) assessments completed after the patient had taken rescue medication or the second dose of study medication, whichever was first, until hour 2 was considered missing. Last observation carried forward (LOCF) was used with the last completed PI/PAR assessments prior to first rescue/second study medication, whichever was first, to impute missing values up to 2 hours.
Outcome measures
| Measure |
Placebo
n=70 Participants
One Placebo tablet after dental surgery
|
Caffeine
n=70 Participants
One Caffeine 100mg tablet after dental surgery
|
Ibuprofen
n=209 Participants
One Ibuprofen 400mg tablet after dental surgery
|
Ibuprofen/Caffeine
n=213 Participants
One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery
|
|---|---|---|---|---|
|
Time-weighted Sum of Pain Relief (PAR) and Pain Intensity Difference (PID) From 0 to 2 Hours (SPRID0-2h)
|
2.059 units on a scale
Standard Error 0.703
|
2.612 units on a scale
Standard Error 0.702
|
6.990 units on a scale
Standard Error 0.408
|
10.584 units on a scale
Standard Error 0.404
|
SECONDARY outcome
Timeframe: 8 hoursPopulation: Patients who used at least one dose of study medication and provided any post-treatment data for the primary efficacy endpoint (FAS)
Duration of pain relief was defined as the time between the administration of first dose of trial medication and first dose of rescue medication or second dose of trial medication, whichever was first. Duration of pain relief was censored at 8 hours.
Outcome measures
| Measure |
Placebo
n=70 Participants
One Placebo tablet after dental surgery
|
Caffeine
n=70 Participants
One Caffeine 100mg tablet after dental surgery
|
Ibuprofen
n=209 Participants
One Ibuprofen 400mg tablet after dental surgery
|
Ibuprofen/Caffeine
n=213 Participants
One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery
|
|---|---|---|---|---|
|
Duration of Pain Relief
|
1.63 hours
Interval 1.6 to 2.07
|
2.08 hours
Interval 1.67 to 3.83
|
7.11 hours
Interval 6.43 to 7.77
|
7.33 hours
Interval 7.05 to 7.77
|
SECONDARY outcome
Timeframe: 8 hoursPopulation: Patients who used at least one dose of study medication and provided any post-treatment data for the primary efficacy endpoint (FAS)
Time to meaningful pain relief was captured by a stopwatch, which was started by the study staff immediately after the administration of the first dose of trial medication and which was to be stopped by the patient as soon as he/she felt meaningful pain relief. Time to meaningful pain relief was censored at 8 hours.
Outcome measures
| Measure |
Placebo
n=70 Participants
One Placebo tablet after dental surgery
|
Caffeine
n=70 Participants
One Caffeine 100mg tablet after dental surgery
|
Ibuprofen
n=209 Participants
One Ibuprofen 400mg tablet after dental surgery
|
Ibuprofen/Caffeine
n=213 Participants
One Ibuprofen 400mg/Caffeine 100mg tablet after dental surgery
|
|---|---|---|---|---|
|
Time to Meaningful Pain Relief
|
NA hours
because more than half of the patients were without meaningful pain relief within 8 h
|
NA hours
because more than half of the patients were without meaningful pain relief within 8 h
|
1.78 hours
Interval 1.48 to 2.02
|
1.13 hours
Interval 0.93 to 1.35
|
Adverse Events
Placebo
Caffeine
Ibuprofen
Ibuprofen/Caffeine
Serious adverse events
| Measure |
Placebo
n=70 participants at risk
Placebo tablet
|
Caffeine
n=70 participants at risk
Caffeine 100mg tablet
|
Ibuprofen
n=279 participants at risk
Ibuprofen 400mg tablet
|
Ibuprofen/Caffeine
n=282 participants at risk
Ibuprofen 400mg / Caffeine 100mg tablet
|
|---|---|---|---|---|
|
Infections and infestations
Oral infection
|
0.00%
0/70 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
0.00%
0/70 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
0.36%
1/279 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
0.00%
0/282 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
Other adverse events
| Measure |
Placebo
n=70 participants at risk
Placebo tablet
|
Caffeine
n=70 participants at risk
Caffeine 100mg tablet
|
Ibuprofen
n=279 participants at risk
Ibuprofen 400mg tablet
|
Ibuprofen/Caffeine
n=282 participants at risk
Ibuprofen 400mg / Caffeine 100mg tablet
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.3%
3/70 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
1.4%
1/70 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
3.2%
9/279 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
8.2%
23/282 • First dose of study drug date/time until drug discontinuation date + 24 hours (inclusive)
Patients at risk and reported adverse events were allocated to the actual treatment patients were exposed to, regardless of the study stage.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER