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Intravenous Tapentadol in Post-Bunionectomy Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01435577
Recruitment Status : Completed
First Posted : September 16, 2011
Results First Posted : June 24, 2013
Last Update Posted : July 2, 2013
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Bunion
Pain
Interventions Drug: Tapentadol
Drug: Matching Placebo
Enrollment 177
Recruitment Details The recruitment period for this trial was from the 26 September 2011 and was completed on the 14 Feb 2012.
Pre-assignment Details

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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 64 65
Completed 47 13
Not Completed 17 52
Reason Not Completed
Adverse Event             10             0
Lack of Efficacy             7             51
Alternative treatment started             0             1
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous Total
Hide Arm/Group Description 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. Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain. Total of all reporting groups
Overall Number of Baseline Participants 64 65 129
Hide Baseline Analysis Population Description
The summary statistics provided for baseline was based on safety population that included 64 subjects in the tapentadol group and 65 in the placebo group. The safety population includes randomized participants that received at least one dose of study drug.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 65 participants 129 participants
41.2  (12.61) 35.8  (12.41) 38.5  (12.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 65 participants 129 participants
Female
57
  89.1%
60
  92.3%
117
  90.7%
Male
7
  10.9%
5
   7.7%
12
   9.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 64 participants 65 participants 129 participants
64 65 129
Baseline pain intensity   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 64 participants 65 participants 129 participants
7.2  (1.41) 7.3  (1.54) 7.2  (1.47)
[1]
Measure Description: Pain intensity assessed prior to the first administration of study medication. Pain intensity is assessed by the participant 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".
1.Primary Outcome
Title Sum of Pain Intensity Differences (SPID 24)
Hide Description 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.
Time Frame Baseline value; up to 24 hours after first study drug administration
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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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-51.23
(-59.93 to -42.52)
25.46
(16.82 to 34.10)
2.Secondary Outcome
Title Mean Pain Intensity Scores at Fixed Time Points
Hide Description 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.
Time Frame Baseline; up to 48 hours
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Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (before first study drug administration) 7.2  (1.41) 7.3  (1.54)
0.25 hours after first dose 3.7  (1.99) 7.1  (1.57)
0.5 hour after first dose 3.1  (1.77) 7.4  (1.63)
1 hour after first dose 3.6  (1.77) 7.8  (1.76)
2 hours after first dose 5.8  (2.03) 8.5  (1.5)
4 hours after first dose 6.1  (1.92) 8.6  (1.46)
6 hours after first dose 6.3  (2.25) 8.7  (1.47)
8 hours after first dose 6.5  (2.29) 8.6  (1.61)
12 hours after first dose 5.2  (2.7) 8.5  (1.67)
16 hours after first dose 3.8  (2.58) 8.2  (2.12)
20 hours after first dose 3.7  (2.52) 8.0  (2.24)
24 hours after first dose 4.1  (2.43) 8.1  (2.08)
36 hours after first dose 3.9  (2.49) 8.0  (2.39)
48 hours after first dose 4.3  (2.56) 8.1  (2.21)
3.Secondary Outcome
Title Pain Intensity Differences at Fixed Time Points
Hide Description 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.
Time Frame Starting at 15 minutes and up to 48 hours after first drug administration
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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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.25 hours after first administration -3.5  (2.22) -0.2  (0.95)
0.5 hours after first administration -4.1  (2.24) 0.1  (1.18)
1 hour after first administration -3.5  (2.07) 0.5  (1.4)
2 hours after first administration -1.3  (2.24) 1.2  (1.39)
4 hours after first dose administration -1.0  (2.09) 1.4  (1.47)
6 hours after first dose administration -0.9  (2.32) 1.4  (1.51)
8 hours after first dose administration -0.7  (2.5) 1.3  (1.58)
12 hours after first dose administration -2.0  (3.01) 1.2  (1.57)
16 hours after first dose administration -3.4  (2.90) 0.9  (1.82)
20 hours after first dose administration -3.5  (2.89) 0.7  (2.08)
24 hours after first dose administration -3.1  (2.65) 0.9  (2.0)
36 hours after first dose administration -3.2  (2.68) 0.8  (2.26)
48 hours after first dose administration -2.9  (2.76) 0.8  (2.11)
4.Secondary Outcome
Title Patient Global Impression of Change After 12 Hours of Treatment
Hide Description 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).
Time Frame Baseline value to 12 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 54 15
Measure Type: Number
Unit of Measure: participants
Very Much Improved 11 0
Much Improved 20 1
Minimally Improved 14 9
No Change 5 4
Minimally Worse 4 1
Much Worse 0 0
Very Much Worse 0 0
5.Secondary Outcome
Title Patients Global Impression of Change After 24 Hours of Treatment
Hide Description 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).
Time Frame Baseline value to 24 hours after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 52 15
Measure Type: Number
Unit of Measure: participants
Very Much Improved 13 0
Much Improved 26 5
Minimally Improved 11 6
No Change 1 2
Minimally Worse 1 2
6.Secondary Outcome
Title Patient Global Impression of Change After 48 Hours of Treatment
Hide Description 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).
Time Frame Baseline value to 48 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 47 13
Measure Type: Number
Unit of Measure: participants
Very Much Improved 19 2
Much Improved 24 8
Minimally Improved 4 2
No Change 0 1
Minimally Worse 0 0
Much Worse 0 0
Very Much Worse 0 0
7.Secondary Outcome
Title Sum of Pain Intensity Differences After 60 Minutes
Hide Description 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.
Time Frame Baseline value to 60 minutes after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-3.65
(-4.01 to -3.3)
0.26
(-0.10 to 0.61)
8.Secondary Outcome
Title Sum of Pain Intensity Differences After 4 Hours
Hide Description 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).
Time Frame Baseline value to 4 hours after first study drug intake
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-6.76
(-7.92 to -5.61)
4.22
(3.07 to 5.37)
9.Secondary Outcome
Title Sum of Pain Intensity Differences After 8 Hours
Hide Description 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).
Time Frame Baseline value to 8 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-9.9
(-12.5 to -7.31)
9.74
(7.17 to 12.32)
10.Secondary Outcome
Title Sum of Pain Intensity Differences After 12 Hours
Hide Description 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).
Time Frame Baseline value to 12 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-14.98
(-19.09 to -10.87)
14.82
(10.74 to 18.90)
11.Secondary Outcome
Title Sum of Pain Intensity Differences After 48 Hours
Hide Description 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).
Time Frame Baseline value to 48 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-122.93
(-143.73 to -102.13)
45.86
(25.22 to 66.5)
12.Secondary Outcome
Title Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 12 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
27 1
13.Secondary Outcome
Title Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 24 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
31 4
14.Secondary Outcome
Title Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 48 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
8 1
15.Secondary Outcome
Title Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 12 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
18 1
16.Secondary Outcome
Title Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 24 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
24 1
17.Secondary Outcome
Title Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores
Hide Description 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.
Time Frame Baseline value to 48 hours after first study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
6 0
18.Secondary Outcome
Title Time to First Rescue Medication
Hide Description The median time to first rescue medication intake (600 mg ibuprofen) in hours.
Time Frame up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Median (95% Confidence Interval)
Unit of Measure: hours
5.4
(4.7 to 7.1)
2.1
(1.9 to 2.3)
19.Secondary Outcome
Title Time to Perceptible Pain Relief
Hide Description 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.
Time Frame up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 65
Median (95% Confidence Interval)
Unit of Measure: hours
0.2
(0.1 to 0.2)
20.Secondary Outcome
Title Time to Meaningful Pain Relief
Hide Description 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.
Time Frame up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous
Hide Arm/Group Description:
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. Values collected after 12 hours were censored, i.e. participants scored as having no meaningful pain relief.
Overall Number of Participants Analyzed 64
Median (95% Confidence Interval)
Unit of Measure: hours
0.3
(0.3 to 0.4)
21.Secondary Outcome
Title Pharmacokinetic Concentrations of Tapentadol
Hide Description 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.
Time Frame 15 minutes to 20 hours after first drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous
Hide Arm/Group Description:
Pharmacokinetic samples were taken from all participants, however only samples from the tapentadol treatment group were analyzed.
Overall Number of Participants Analyzed 17
Mean (Full Range)
Unit of Measure: ng/mL
15 minutes after first infusion (n = 17)
201.2
(69.5 to 593)
30 minutes after first infusion (n = 17)
99.5
(59.8 to 164)
60 minutes after first infusion (n = 17)
76.4
(43.3 to 103)
4 hours after end of first infusion (n = 13)
38.2
(21.5 to 60.5)
3.5 hours after end of fifth infusion (n = 13)
73.2
(39.4 to 106)
4 hours after end of fifth infusion (n = 9)
70.3
(34.4 to 105)
22.Secondary Outcome
Title Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
Hide Description 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.
Time Frame 15 minutes to 20 hours after first drug administration
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Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous
Hide Arm/Group Description:
Pharmacokinetic samples were taken from all participants, however only samples from the tapentadol treatment group were analyzed.
Overall Number of Participants Analyzed 17
Mean (Full Range)
Unit of Measure: ng/mL
15 minutes after first infusion (n = 15)
26.4
(11.6 to 88.2)
30 minutes after first infusion (n = 17)
290.4
(111 to 515)
60 minutes after first infusion (n = 17)
488.2
(287 to 666)
4 hours after end of first infusion (n = 13)
452.4
(265 to 651)
3.5 hours after end of fifth infusion (n = 13)
1048.7
(680 to 1410)
4 hours after end of fifth infusion (n = 9)
945.1
(608 to 1200)
23.Secondary Outcome
Title Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
Hide Description 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.
Time Frame Baseline; for the first 6 administrations
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Hide Analysis Population Description
Participants contributing data.
Arm/Group Title Tapentadol Intravenous
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: units on a scale
Prior to first dose (n = 64) 7.2  (1.41)
1 hour after first dose (n = 64) 3.6  (1.77)
prior to second dose (n = 63) 7.3  (1.59)
1 hour after second dose (n = 63) 4.7  (2.09)
prior to third dose (n = 58) 7.2  (1.6)
1 hour after third dose (n = 57) 6.1  (2.71)
prior to fourth dose (n = 54) 6.6  (2.21)
1 hour after fourth dose (n = 54) 4.1  (2.96)
prior to fifth dose (n = 53) 4.9  (2.57)
1 hour after fifth dose (n = 53) 2.7  (2.47)
prior to sixth dose (n = 53) 4.5  (2.35)
24.Secondary Outcome
Title Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
Hide Description 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.
Time Frame Baseline; for the first 6 administrations
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Hide Analysis Population Description
Participants contributing data (indicated in brackets)
Arm/Group Title Matching Placebo Intravenous
Hide Arm/Group Description:
Matching Placebo will be given by intravenous infusion. Matching Placebo will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by Tapentadol alone.
Overall Number of Participants Analyzed 65
Mean (Standard Deviation)
Unit of Measure: units on a scale
Prior to first dose (n = 65) 7.3  (1.54)
1 hour after first dose (n = 64) 7.8  (1.76)
prior to second dose (n = 63) 8.4  (1.30)
1 hour after second dose (n = 63) 8.6  (1.53)
prior to third dose (n = 23) 7.9  (1.65)
1 hour after third dose (n = 23) 7.9  (1.77)
prior to fourth dose (n = 19) 7.3  (2.05)
1 hour after fourth dose (n = 19) 7.1  (2.07)
prior to fifth dose (n = 15) 5.8  (2.04)
1 hour after fifth dose (n = 15) 5.2  (2.24)
prior to sixth dose (n = 15) 5.7  (2.13)
1 hour after sixth dose (n = 15) 4.8  (1.76)
25.Post-Hoc Outcome
Title Number of Participants Scored as a Responder Based on Patient Global Impression of Change
Hide Description 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.
Time Frame Fixed time points at 12, 24 and 48 hours after baseline
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Hide Analysis Population Description
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.
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description:
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.
Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Overall Number of Participants Analyzed 64 65
Measure Type: Number
Unit of Measure: participants
Responders 12 hours after first dose 31 1
Responders 24 hours after first dose 39 5
Responders 48 hours after first dose 43 10
Time Frame From administration of first dose of study drug up to 4 days after the administration of the last dose of study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tapentadol Intravenous Matching Placebo Intravenous
Hide Arm/Group Description 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. Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
All-Cause Mortality
Tapentadol Intravenous Matching Placebo Intravenous
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tapentadol Intravenous Matching Placebo Intravenous
Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)   0/65 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tapentadol Intravenous Matching Placebo Intravenous
Affected / at Risk (%) Affected / at Risk (%)
Total   63/64 (98.44%)   37/65 (56.92%) 
Cardiac disorders     
Arrhythmia * 1  0/64 (0.00%)  1/65 (1.54%) 
Palpitations * 1  0/64 (0.00%)  1/65 (1.54%) 
Tachycardia * 1  0/64 (0.00%)  2/65 (3.08%) 
Eye disorders     
Vision blurred * 1  1/64 (1.56%)  0/65 (0.00%) 
Visual impairment * 1  1/64 (1.56%)  0/65 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  1/64 (1.56%)  0/65 (0.00%) 
Abdominal distension * 1  0/64 (0.00%)  1/65 (1.54%) 
Constipation * 1  3/64 (4.69%)  1/65 (1.54%) 
Diarrhoea * 1  1/64 (1.56%)  0/65 (0.00%) 
Dry mouth * 1  6/64 (9.38%)  0/65 (0.00%) 
Haematemesis * 1  1/64 (1.56%)  0/65 (0.00%) 
Nausea * 1  43/64 (67.19%)  27/65 (41.54%) 
Vomiting * 1  29/64 (45.31%)  11/65 (16.92%) 
General disorders     
Chest discomfort * 1  1/64 (1.56%)  0/65 (0.00%) 
Chills * 1  2/64 (3.13%)  0/65 (0.00%) 
Feeling abnormal * 1  3/64 (4.69%)  0/65 (0.00%) 
Feeling hot * 1  13/64 (20.31%)  1/65 (1.54%) 
Feeling jittery * 1  1/64 (1.56%)  0/65 (0.00%) 
Infusion site erythema  1  1/64 (1.56%)  0/65 (0.00%) 
Infusion site extravasation  1  5/64 (7.81%)  1/65 (1.54%) 
Infusion site phlebitis  1  9/64 (14.06%)  0/65 (0.00%) 
Injection site extravasation  1  1/64 (1.56%)  0/65 (0.00%) 
Injection site induration * 1  1/64 (1.56%)  0/65 (0.00%) 
Injection site phlebitis * 1  1/64 (1.56%)  0/65 (0.00%) 
Local swelling * 1  1/64 (1.56%)  0/65 (0.00%) 
Pain * 1  1/64 (1.56%)  0/65 (0.00%) 
Pyrexia * 1  1/64 (1.56%)  1/65 (1.54%) 
Vessel puncture site haematoma  1  0/64 (0.00%)  1/65 (1.54%) 
Immune system disorders     
Seasonal allergy * 1  1/64 (1.56%)  0/65 (0.00%) 
Infections and infestations     
Helicobacter infection * 1  1/64 (1.56%)  0/65 (0.00%) 
Upper respiratory tract infection * 1  1/64 (1.56%)  0/65 (0.00%) 
Injury, poisoning and procedural complications     
Contusion * 1  1/64 (1.56%)  0/65 (0.00%) 
Excoriation * 1  0/64 (0.00%)  1/65 (1.54%) 
Laceration * 1  1/64 (1.56%)  0/65 (0.00%) 
Tongue injury * 1  0/64 (0.00%)  1/65 (1.54%) 
Investigations     
Blood creatine phosphokinase increased  1  2/64 (3.13%)  0/65 (0.00%) 
Haematocrit decreased  1  1/64 (1.56%)  0/65 (0.00%) 
Haemoglobin decreased  1  1/64 (1.56%)  0/65 (0.00%) 
Oxygen saturation decreased  1  11/64 (17.19%)  0/65 (0.00%) 
Red blood cell count decreased  1  1/64 (1.56%)  0/65 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  5/64 (7.81%)  1/65 (1.54%) 
Hypokalaemia  1  0/64 (0.00%)  1/65 (1.54%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/64 (1.56%)  0/65 (0.00%) 
Muscle spasms * 1  2/64 (3.13%)  1/65 (1.54%) 
Muscle twitching * 1  2/64 (3.13%)  0/65 (0.00%) 
Neck pain * 1  1/64 (1.56%)  0/65 (0.00%) 
Nervous system disorders     
Cognitive disorder * 1  2/64 (3.13%)  0/65 (0.00%) 
Dizziness * 1  25/64 (39.06%)  8/65 (12.31%) 
Dysarthria * 1  2/64 (3.13%)  0/65 (0.00%) 
Headache * 1  9/64 (14.06%)  2/65 (3.08%) 
Hypoaesthesia * 1  0/64 (0.00%)  1/65 (1.54%) 
Myoclonus * 1  1/64 (1.56%)  0/65 (0.00%) 
Nystagmus * 1  2/64 (3.13%)  0/65 (0.00%) 
Paraesthesia * 1  0/64 (0.00%)  1/65 (1.54%) 
Somnolence * 1  27/64 (42.19%)  2/65 (3.08%) 
Tremor * 1  1/64 (1.56%)  1/65 (1.54%) 
Psychiatric disorders     
Nightmare * 1  2/64 (3.13%)  0/65 (0.00%) 
Renal and urinary disorders     
Micturition urgency * 1  1/64 (1.56%)  0/65 (0.00%) 
Pyuria  1  1/64 (1.56%)  0/65 (0.00%) 
Urinary retention * 1  1/64 (1.56%)  0/65 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  1/64 (1.56%)  0/65 (0.00%) 
Cough * 1  1/64 (1.56%)  0/65 (0.00%) 
Dry throat * 1  1/64 (1.56%)  0/65 (0.00%) 
Dyspnoea * 1  1/64 (1.56%)  0/65 (0.00%) 
Nasal congestion * 1  2/64 (3.13%)  0/65 (0.00%) 
Oropharyngeal pain * 1  1/64 (1.56%)  0/65 (0.00%) 
Pharyngeal hypoaesthesia * 1  1/64 (1.56%)  0/65 (0.00%) 
Productive cough * 1  1/64 (1.56%)  0/65 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  2/64 (3.13%)  0/65 (0.00%) 
Hyperhidrosis * 1  11/64 (17.19%)  2/65 (3.08%) 
Pruritus * 1  10/64 (15.63%)  4/65 (6.15%) 
Rash * 1  3/64 (4.69%)  1/65 (1.54%) 
Rash pruritic * 1  1/64 (1.56%)  0/65 (0.00%) 
Vascular disorders     
Hypertension  1  0/64 (0.00%)  2/65 (3.08%) 
Hypotension  1  1/64 (1.56%)  1/65 (1.54%) 
Pallor * 1  0/64 (0.00%)  2/65 (3.08%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Director of Clinical Trials
Organization: Grünenthal GmbH
Phone: +241 569 3223
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT01435577     History of Changes
Other Study ID Numbers: 295054
First Submitted: September 15, 2011
First Posted: September 16, 2011
Results First Submitted: March 5, 2013
Results First Posted: June 24, 2013
Last Update Posted: July 2, 2013