Trial Outcomes & Findings for Intravenous Tapentadol in Post-Bunionectomy Pain (NCT NCT01435577)
NCT ID: NCT01435577
Last Updated: 2019-10-28
Results Overview
Pain Intensity assessed at predefined time points (at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 20 and 24 hours after first drug administration) over a 24 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NRS values - baseline NRS values) were analyzed. Negative SPID24 values indicate a decrease in pain intensity and positive values indicate an increase in pain intensity since baseline.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
177 participants
Primary outcome timeframe
Baseline value; up to 24 hours after first study drug administration
Results posted on
2019-10-28
Participant Flow
The recruitment period for this trial was from the 26 September 2011 and was completed on the 14 Feb 2012.
177 participants signed informed consent. * 132 participants underwent surgery. * 131 participants reported a pain intensity that qualified them to enter the trial, i.e. one participant did not report sufficient pain to enter the trial. * 129 participants were randomized to receive treatment.
Participant milestones
| Measure |
Tapentadol Intravenous
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
64 Participants Randomized, 64 Participants in the Safety Set (SAF), 64 Participants in the Full Analysis Set (FAS). The FAS comprised all randomized subjects who were administered at least 1 dose and had a baseline pain assessment.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
65 Randomized participants, 65 Participants in the Safety Set (SAF), 65 Participants in the Full Analysis Set(FAS). The FAS comprised all randomized subjects who were administered at least 1 dose and had a baseline pain assessment.
|
|---|---|---|
|
Overall Study
STARTED
|
64
|
65
|
|
Overall Study
COMPLETED
|
47
|
13
|
|
Overall Study
NOT COMPLETED
|
17
|
52
|
Reasons for withdrawal
| Measure |
Tapentadol Intravenous
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
64 Participants Randomized, 64 Participants in the Safety Set (SAF), 64 Participants in the Full Analysis Set (FAS). The FAS comprised all randomized subjects who were administered at least 1 dose and had a baseline pain assessment.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
65 Randomized participants, 65 Participants in the Safety Set (SAF), 65 Participants in the Full Analysis Set(FAS). The FAS comprised all randomized subjects who were administered at least 1 dose and had a baseline pain assessment.
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
0
|
|
Overall Study
Lack of Efficacy
|
7
|
51
|
|
Overall Study
Alternative treatment started
|
0
|
1
|
Baseline Characteristics
Intravenous Tapentadol in Post-Bunionectomy Pain
Baseline characteristics by cohort
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by Tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
Total
n=129 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.2 years
STANDARD_DEVIATION 12.61 • n=99 Participants
|
35.8 years
STANDARD_DEVIATION 12.41 • n=107 Participants
|
38.5 years
STANDARD_DEVIATION 12.75 • n=206 Participants
|
|
Sex: Female, Male
Female
|
57 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
117 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
64 participants
n=99 Participants
|
65 participants
n=107 Participants
|
129 participants
n=206 Participants
|
|
Baseline pain intensity
|
7.2 units on a scale
STANDARD_DEVIATION 1.41 • n=99 Participants
|
7.3 units on a scale
STANDARD_DEVIATION 1.54 • n=107 Participants
|
7.2 units on a scale
STANDARD_DEVIATION 1.47 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline value; up to 24 hours after first study drug administrationPopulation: Full Analysis Set (FAS): patients who took at least one dose of study medication, had a baseline value, and had at least one post-baseline measurement; Last Observation Carried Forward (LOCF) after dropout, and LOCF for 6 hours after each rescue medication intake.
Pain Intensity assessed at predefined time points (at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 20 and 24 hours after first drug administration) over a 24 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NRS values - baseline NRS values) were analyzed. Negative SPID24 values indicate a decrease in pain intensity and positive values indicate an increase in pain intensity since baseline.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences (SPID 24)
|
-51.23 units on a scale
Interval -59.93 to -42.52
|
25.46 units on a scale
Interval 16.82 to 34.1
|
SECONDARY outcome
Timeframe: Baseline; up to 48 hoursPopulation: Full Analysis Set (FAS). Participants who took at least one dose of study medication, had a baseline value, and had at least one post-baseline measurement; Last Observation Carried Forward (LOCF) after dropout, and LOCF for 6 hours after each rescue medication intake.
The mean pain intensity at fixed time points in the trial for all participants is listed. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Mean Pain Intensity Scores at Fixed Time Points
Baseline (before first study drug administration)
|
7.2 units on a scale
Standard Deviation 1.41
|
7.3 units on a scale
Standard Deviation 1.54
|
|
Mean Pain Intensity Scores at Fixed Time Points
0.25 hours after first dose
|
3.7 units on a scale
Standard Deviation 1.99
|
7.1 units on a scale
Standard Deviation 1.57
|
|
Mean Pain Intensity Scores at Fixed Time Points
0.5 hour after first dose
|
3.1 units on a scale
Standard Deviation 1.77
|
7.4 units on a scale
Standard Deviation 1.63
|
|
Mean Pain Intensity Scores at Fixed Time Points
1 hour after first dose
|
3.6 units on a scale
Standard Deviation 1.77
|
7.8 units on a scale
Standard Deviation 1.76
|
|
Mean Pain Intensity Scores at Fixed Time Points
2 hours after first dose
|
5.8 units on a scale
Standard Deviation 2.03
|
8.5 units on a scale
Standard Deviation 1.5
|
|
Mean Pain Intensity Scores at Fixed Time Points
4 hours after first dose
|
6.1 units on a scale
Standard Deviation 1.92
|
8.6 units on a scale
Standard Deviation 1.46
|
|
Mean Pain Intensity Scores at Fixed Time Points
6 hours after first dose
|
6.3 units on a scale
Standard Deviation 2.25
|
8.7 units on a scale
Standard Deviation 1.47
|
|
Mean Pain Intensity Scores at Fixed Time Points
8 hours after first dose
|
6.5 units on a scale
Standard Deviation 2.29
|
8.6 units on a scale
Standard Deviation 1.61
|
|
Mean Pain Intensity Scores at Fixed Time Points
12 hours after first dose
|
5.2 units on a scale
Standard Deviation 2.7
|
8.5 units on a scale
Standard Deviation 1.67
|
|
Mean Pain Intensity Scores at Fixed Time Points
16 hours after first dose
|
3.8 units on a scale
Standard Deviation 2.58
|
8.2 units on a scale
Standard Deviation 2.12
|
|
Mean Pain Intensity Scores at Fixed Time Points
20 hours after first dose
|
3.7 units on a scale
Standard Deviation 2.52
|
8.0 units on a scale
Standard Deviation 2.24
|
|
Mean Pain Intensity Scores at Fixed Time Points
24 hours after first dose
|
4.1 units on a scale
Standard Deviation 2.43
|
8.1 units on a scale
Standard Deviation 2.08
|
|
Mean Pain Intensity Scores at Fixed Time Points
36 hours after first dose
|
3.9 units on a scale
Standard Deviation 2.49
|
8.0 units on a scale
Standard Deviation 2.39
|
|
Mean Pain Intensity Scores at Fixed Time Points
48 hours after first dose
|
4.3 units on a scale
Standard Deviation 2.56
|
8.1 units on a scale
Standard Deviation 2.21
|
SECONDARY outcome
Timeframe: Starting at 15 minutes and up to 48 hours after first drug administrationPopulation: Full Analysis Set (FAS): Participants who took at least one dose of study medication, had a baseline value, and had at least one post-baseline measurement; Last Observation Carried Forward (LOCF) after dropout, and LOCF for 6 hours after each rescue medication intake.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between baseline pain intensity (prior to the first dose) and the pain intensity at the time. A negative number indicates a decrease in pain in the whole treatment group. The greater the negative pain intensity difference value the greater the pain relief in the treatment arm. A score of 0 indicates that there has been no change in pain in a treatment group. A positive value indicates an increase in pain in the treatment group.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Pain Intensity Differences at Fixed Time Points
0.25 hours after first administration
|
-3.5 units on a scale
Standard Deviation 2.22
|
-0.2 units on a scale
Standard Deviation 0.95
|
|
Pain Intensity Differences at Fixed Time Points
0.5 hours after first administration
|
-4.1 units on a scale
Standard Deviation 2.24
|
0.1 units on a scale
Standard Deviation 1.18
|
|
Pain Intensity Differences at Fixed Time Points
1 hour after first administration
|
-3.5 units on a scale
Standard Deviation 2.07
|
0.5 units on a scale
Standard Deviation 1.4
|
|
Pain Intensity Differences at Fixed Time Points
2 hours after first administration
|
-1.3 units on a scale
Standard Deviation 2.24
|
1.2 units on a scale
Standard Deviation 1.39
|
|
Pain Intensity Differences at Fixed Time Points
4 hours after first dose administration
|
-1.0 units on a scale
Standard Deviation 2.09
|
1.4 units on a scale
Standard Deviation 1.47
|
|
Pain Intensity Differences at Fixed Time Points
6 hours after first dose administration
|
-0.9 units on a scale
Standard Deviation 2.32
|
1.4 units on a scale
Standard Deviation 1.51
|
|
Pain Intensity Differences at Fixed Time Points
8 hours after first dose administration
|
-0.7 units on a scale
Standard Deviation 2.5
|
1.3 units on a scale
Standard Deviation 1.58
|
|
Pain Intensity Differences at Fixed Time Points
12 hours after first dose administration
|
-2.0 units on a scale
Standard Deviation 3.01
|
1.2 units on a scale
Standard Deviation 1.57
|
|
Pain Intensity Differences at Fixed Time Points
16 hours after first dose administration
|
-3.4 units on a scale
Standard Deviation 2.90
|
0.9 units on a scale
Standard Deviation 1.82
|
|
Pain Intensity Differences at Fixed Time Points
20 hours after first dose administration
|
-3.5 units on a scale
Standard Deviation 2.89
|
0.7 units on a scale
Standard Deviation 2.08
|
|
Pain Intensity Differences at Fixed Time Points
24 hours after first dose administration
|
-3.1 units on a scale
Standard Deviation 2.65
|
0.9 units on a scale
Standard Deviation 2.0
|
|
Pain Intensity Differences at Fixed Time Points
36 hours after first dose administration
|
-3.2 units on a scale
Standard Deviation 2.68
|
0.8 units on a scale
Standard Deviation 2.26
|
|
Pain Intensity Differences at Fixed Time Points
48 hours after first dose administration
|
-2.9 units on a scale
Standard Deviation 2.76
|
0.8 units on a scale
Standard Deviation 2.11
|
SECONDARY outcome
Timeframe: Baseline value to 12 hours after first study drug administrationPopulation: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Outcome measures
| Measure |
Tapentadol Intravenous
n=54 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=15 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Patient Global Impression of Change After 12 Hours of Treatment
Very Much Improved
|
11 participants
|
0 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
Much Improved
|
20 participants
|
1 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
Minimally Improved
|
14 participants
|
9 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
No Change
|
5 participants
|
4 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
Minimally Worse
|
4 participants
|
1 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
Much Worse
|
0 participants
|
0 participants
|
|
Patient Global Impression of Change After 12 Hours of Treatment
Very Much Worse
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline value to 24 hours after study drug administrationPopulation: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Outcome measures
| Measure |
Tapentadol Intravenous
n=52 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=15 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Patients Global Impression of Change After 24 Hours of Treatment
Very Much Improved
|
13 participants
|
0 participants
|
|
Patients Global Impression of Change After 24 Hours of Treatment
Much Improved
|
26 participants
|
5 participants
|
|
Patients Global Impression of Change After 24 Hours of Treatment
Minimally Improved
|
11 participants
|
6 participants
|
|
Patients Global Impression of Change After 24 Hours of Treatment
No Change
|
1 participants
|
2 participants
|
|
Patients Global Impression of Change After 24 Hours of Treatment
Minimally Worse
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline value to 48 hours after first study drug administrationPopulation: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Outcome measures
| Measure |
Tapentadol Intravenous
n=47 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=13 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Patient Global Impression of Change After 48 Hours of Treatment
Very Much Improved
|
19 participants
|
2 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
Much Improved
|
24 participants
|
8 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
Minimally Improved
|
4 participants
|
2 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
No Change
|
0 participants
|
1 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
Minimally Worse
|
0 participants
|
0 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
Much Worse
|
0 participants
|
0 participants
|
|
Patient Global Impression of Change After 48 Hours of Treatment
Very Much Worse
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline value to 60 minutes after first study drug administrationPopulation: Full analysis set.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 60 minutes was calculated. If the value is negative then the baseline pain intensity was greater than the pain intensity measured after dosing.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences After 60 Minutes
|
-3.65 units on a scale
Interval -4.01 to -3.3
|
0.26 units on a scale
Interval -0.1 to 0.61
|
SECONDARY outcome
Timeframe: Baseline value to 4 hours after first study drug intakePopulation: Full analysis set. Primary imputation method was analyzed: Last Observation Carried Forward (LOCF) after dropout, and LOCF for 6 h after each rescue medication intake.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 4 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences After 4 Hours
|
-6.76 units on a scale
Interval -7.92 to -5.61
|
4.22 units on a scale
Interval 3.07 to 5.37
|
SECONDARY outcome
Timeframe: Baseline value to 8 hours after first study drug administrationPopulation: Full Analysis Set.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 8 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences After 8 Hours
|
-9.9 units on a scale
Interval -12.5 to -7.31
|
9.74 units on a scale
Interval 7.17 to 12.32
|
SECONDARY outcome
Timeframe: Baseline value to 12 hours after first study drug administrationPopulation: Full Analysis Set.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 12 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences After 12 Hours
|
-14.98 units on a scale
Interval -19.09 to -10.87
|
14.82 units on a scale
Interval 10.74 to 18.9
|
SECONDARY outcome
Timeframe: Baseline value to 48 hours after first study drug administrationPopulation: Full Analysis Set.
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 60 minutes was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Sum of Pain Intensity Differences After 48 Hours
|
-122.93 units on a scale
Interval -143.73 to -102.13
|
45.86 units on a scale
Interval 25.22 to 66.5
|
SECONDARY outcome
Timeframe: Baseline value to 12 hours after first study drug administrationPopulation: Full analysis set.
Individual participant response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 12 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores
|
27 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline value to 24 hours after first study drug administrationPopulation: Full analysis set.
Individual participant response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 24 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores
|
31 participants
|
4 participants
|
SECONDARY outcome
Timeframe: Baseline value to 48 hours after first study drug administrationPopulation: Full analysis set.
Individual participants response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 48 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores
|
8 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline value to 12 hours after first study drug administrationPopulation: Full analysis set.
Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 12 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores
|
18 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline value to 24 hours after first study drug administrationPopulation: Full analysis set.
Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 24 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores
|
24 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline value to 48 hours after first study drug administrationPopulation: Full analysis set.
Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 48 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores
|
6 participants
|
0 participants
|
SECONDARY outcome
Timeframe: up to 48 hoursPopulation: Full analysis set.
The median time to first rescue medication intake (600 mg ibuprofen) in hours.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Time to First Rescue Medication
|
5.4 hours
Interval 4.7 to 7.1
|
2.1 hours
Interval 1.9 to 2.3
|
SECONDARY outcome
Timeframe: up to 48 hoursPopulation: Participants without pain relief (as measured by the double stopwatch method) were censored at 12 hours from the initial dose or at the time of early withdrawal from the Double-blind Treatment Period, whichever occurred first. Time to perceptible pain relief is not reported for matching placebo arms because of the high number of discontinuations.
When the participant began to feel any pain-relieving effect after the administration of the first dose they were requested to stop the first stopwatch. The time was noted. This measured when the participant first felt any difference in the pain.
Outcome measures
| Measure |
Tapentadol Intravenous
n=65 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Time to Perceptible Pain Relief
|
0.2 hours
Interval 0.1 to 0.2
|
—
|
SECONDARY outcome
Timeframe: up to 48 hoursPopulation: Participants without pain relief (as measured by the double stopwatch method) were censored at 12 hours from the initial dose or at the time of early withdrawal from the Double-blind Treatment Period, whichever occurred first. Time in hours to meaningful pain relief are not reported for matching placebo arm due to the high discontinuation rate.
The participant was instructed to stop the stopwatch when they had meaningful pain relief. That is, when the pain relief made a real difference, after the first drug administration.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Time to Meaningful Pain Relief
|
0.3 hours
Interval 0.3 to 0.4
|
—
|
SECONDARY outcome
Timeframe: 15 minutes to 20 hours after first drug administrationPopulation: Participants in the placebo arm were not analyzed. Only those participants contributing data were analyzed. Participants that had an early second study drug administration were not part of the analysis.
Tapentadol concentrations were measured in participants in the tapentadol treatment arm. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Outcome measures
| Measure |
Tapentadol Intravenous
n=17 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Pharmacokinetic Concentrations of Tapentadol
15 minutes after first infusion
|
201.2 ng/mL
Interval 69.5 to 593.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol
30 minutes after first infusion
|
99.5 ng/mL
Interval 59.8 to 164.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol
60 minutes after first infusion
|
76.4 ng/mL
Interval 43.3 to 103.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol
4 hours after end of first infusion
|
38.2 ng/mL
Interval 21.5 to 60.5
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol
3.5 hours after end of fifth infusion
|
73.2 ng/mL
Interval 39.4 to 106.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol
4 hours after end of fifth infusion
|
70.3 ng/mL
Interval 34.4 to 105.0
|
—
|
SECONDARY outcome
Timeframe: 15 minutes to 20 hours after first drug administrationPopulation: Participants in the placebo arm were not analyzed. Only those participants contributing data were analyzed. Participants that had an early second study drug administration were not part of the analysis.
Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants in the tapentadol treatment arm. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Outcome measures
| Measure |
Tapentadol Intravenous
n=17 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
15 minutes after first infusion
|
26.4 ng/mL
Interval 11.6 to 88.2
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
30 minutes after first infusion
|
290.4 ng/mL
Interval 111.0 to 515.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
60 minutes after first infusion
|
488.2 ng/mL
Interval 287.0 to 666.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
4 hours after end of first infusion
|
452.4 ng/mL
Interval 265.0 to 651.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
3.5 hours after end of fifth infusion
|
1048.7 ng/mL
Interval 680.0 to 1410.0
|
—
|
|
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
4 hours after end of fifth infusion
|
945.1 ng/mL
Interval 608.0 to 1200.0
|
—
|
SECONDARY outcome
Timeframe: Baseline; for the first 6 administrationsPopulation: Participants contributing data.
The pain intensity at the relative time points are the pain intensity before and one hour after study drug administration. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
Prior to first dose (n = 64)
|
7.2 units on a scale
Standard Deviation 1.41
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
1 hour after first dose (n = 64)
|
3.6 units on a scale
Standard Deviation 1.77
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
prior to second dose
|
7.3 units on a scale
Standard Deviation 1.59
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
1 hour after second dose
|
4.7 units on a scale
Standard Deviation 2.09
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
prior to third dose
|
7.2 units on a scale
Standard Deviation 1.6
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
1 hour after third dose
|
6.1 units on a scale
Standard Deviation 2.71
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
prior to fourth dose
|
6.6 units on a scale
Standard Deviation 2.21
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
1 hour after fourth dose
|
4.1 units on a scale
Standard Deviation 2.96
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
prior to fifth dose
|
4.9 units on a scale
Standard Deviation 2.57
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
1 hour after fifth dose
|
2.7 units on a scale
Standard Deviation 2.47
|
—
|
|
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
prior to sixth dose
|
4.5 units on a scale
Standard Deviation 2.35
|
—
|
SECONDARY outcome
Timeframe: Baseline; for the first 6 administrationsPopulation: Participants contributing data (indicated in brackets)
The pain intensity at the relative time points are the pain intensity before and one hour after study drug administration. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.
Outcome measures
| Measure |
Tapentadol Intravenous
n=65 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
Prior to first dose
|
7.3 units on a scale
Standard Deviation 1.54
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after first dose
|
7.8 units on a scale
Standard Deviation 1.76
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
prior to second dose
|
8.4 units on a scale
Standard Deviation 1.30
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after second dose
|
8.6 units on a scale
Standard Deviation 1.53
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
prior to third dose
|
7.9 units on a scale
Standard Deviation 1.65
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after third dose
|
7.9 units on a scale
Standard Deviation 1.77
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
prior to fourth dose
|
7.3 units on a scale
Standard Deviation 2.05
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after fourth dose
|
7.1 units on a scale
Standard Deviation 2.07
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
prior to fifth dose
|
5.8 units on a scale
Standard Deviation 2.04
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after fifth dose
|
5.2 units on a scale
Standard Deviation 2.24
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
prior to sixth dose
|
5.7 units on a scale
Standard Deviation 2.13
|
—
|
|
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
1 hour after sixth dose
|
4.8 units on a scale
Standard Deviation 1.76
|
—
|
POST_HOC outcome
Timeframe: Fixed time points at 12, 24 and 48 hours after baselinePopulation: Participants with early second dose the PGIC assessment from End-of-double-blind Treatment was taken as the 48 hours value. Assessments done more than 4.5 hours after the 12th infusion were excluded from analysis and participants were considered non-responders.
Responders are those participants with Patient Global Impression of Change (PGIC) values "Much improved", or "Very much improved". Participants with missing value are considered non-responders.
Outcome measures
| Measure |
Tapentadol Intravenous
n=64 Participants
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by tapentadol alone.
|
Matching Placebo Intravenous
n=65 Participants
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Number of Participants Scored as a Responder Based on Patient Global Impression of Change
Responders 12 hours after first dose
|
31 participants
|
1 participants
|
|
Number of Participants Scored as a Responder Based on Patient Global Impression of Change
Responders 24 hours after first dose
|
39 participants
|
5 participants
|
|
Number of Participants Scored as a Responder Based on Patient Global Impression of Change
Responders 48 hours after first dose
|
43 participants
|
10 participants
|
Adverse Events
Tapentadol Intravenous
Serious events: 0 serious events
Other events: 63 other events
Deaths: 0 deaths
Matching Placebo Intravenous
Serious events: 0 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tapentadol Intravenous
n=64 participants at risk
Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by Tapentadol alone.
|
Matching Placebo Intravenous
n=65 participants at risk
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Chest discomfort
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Chills
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Cognitive disorder
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
4.7%
3/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.8%
5/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Dizziness
|
39.1%
25/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
12.3%
8/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Dry mouth
|
9.4%
6/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Dysarthria
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Feeling abnormal
|
4.7%
3/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Feeling hot
|
20.3%
13/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Feeling jittery
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Haematemesis
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Investigations
Haematocrit decreased
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Investigations
Haemoglobin decreased
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Headache
|
14.1%
9/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Infections and infestations
Helicobacter infection
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
17.2%
11/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Vascular disorders
Hypertension
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Vascular disorders
Hypotension
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Infusion site erythema
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Infusion site extravasation
|
7.8%
5/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Infusion site phlebitis
|
14.1%
9/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Injection site extravasation
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Injection site induration
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Injection site phlebitis
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Laceration
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Local swelling
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Renal and urinary disorders
Micturition urgency
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Myoclonus
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
67.2%
43/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
41.5%
27/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Psychiatric disorders
Nightmare
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Nystagmus
|
3.1%
2/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Investigations
Oxygen saturation decreased
|
17.2%
11/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Pain
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Vascular disorders
Pallor
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Cardiac disorders
Palpitations
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal hypoaesthesia
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.6%
10/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
6.2%
4/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Pyrexia
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Renal and urinary disorders
Pyuria
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.7%
3/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Investigations
Red blood cell count decreased
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Immune system disorders
Seasonal allergy
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Somnolence
|
42.2%
27/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
3.1%
2/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Tongue injury
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Nervous system disorders
Tremor
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Renal and urinary disorders
Urinary retention
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
1.5%
1/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Eye disorders
Vision blurred
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Eye disorders
Visual impairment
|
1.6%
1/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
0.00%
0/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
45.3%
29/64 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
16.9%
11/65 • From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
|
Additional Information
Director of Clinical Trials
Grünenthal GmbH
Phone: +241 569 3223
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
- Publication restrictions are in place
Restriction type: OTHER