Bunion, Pain
Conditions
Keywords
Bunionectomy, Postsurgical Pain, Acute Pain
Brief summary
The purpose of this trial is to established the safety and efficacy of multiple dose treatment with tapentadol IV in an adult population with moderate to severe pain following bunionectomy.
Interventions
DRUGTapentadol
30 mg per administration, maximum 12 administrations over 48 hours
DRUGMatching Placebo
Maximum 12 administrations over 48 hours
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Scheduled to undergo primary unilateral first metatarsal bunionectomy * Female patients must be postmenopausal, surgically sterile, or practicing an effective method of birth control if they are sexually active * Qualifying pain intensity (within a maximum of 5 hours after the last surgical stitch) and Baseline pain intensity (last pain score measured within 10 minutes before dosing) 5 on an 11-point (0 to 10) pain intensity numerical rating scale (NRS).
Exclusion criteria
* History of malignancy within the past 2 years * Current or history of alcohol or drug abuse. * Clinically relevant pulmonary, gastrointestinal, endocrine, metabolic, neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately * History of seizure disorder, epilepsy, or any condition that would put the subject at risk of seizures * Severely impaired renal function * Moderately or severely impaired hepatic function * Contraindications, or a history of allergy or hypersensitivity, to tapentadol, ibuprofen, or excipients * Use of prohibited concomitant medication, or not allowed use of restricted concomitant medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Differences (SPID 24) | Baseline value; up to 24 hours after first study drug administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Differences at Fixed Time Points | Starting at 15 minutes and up to 48 hours after first drug administration | 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. |
| Patient Global Impression of Change After 12 Hours of Treatment | Baseline value to 12 hours after first study drug administration | 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). |
| Patients Global Impression of Change After 24 Hours of Treatment | Baseline value to 24 hours after study drug administration | 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). |
| Patient Global Impression of Change After 48 Hours of Treatment | Baseline value to 48 hours after first study drug administration | 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). |
| Sum of Pain Intensity Differences After 60 Minutes | Baseline value to 60 minutes after first study drug administration | 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. |
| Sum of Pain Intensity Differences After 4 Hours | Baseline value to 4 hours after first study drug 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). |
| Sum of Pain Intensity Differences After 8 Hours | Baseline value to 8 hours after first study drug administration | 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). |
| Sum of Pain Intensity Differences After 12 Hours | Baseline value to 12 hours after first study drug administration | 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). |
| Sum of Pain Intensity Differences After 48 Hours | Baseline value to 48 hours after first study drug administration | 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). |
| Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores | Baseline value to 12 hours after first study drug administration | 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. |
| Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores | Baseline value to 24 hours after first study drug administration | 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. |
| Mean Pain Intensity Scores at Fixed Time Points | Baseline; up to 48 hours | 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. |
| Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores | Baseline value to 12 hours after first study drug administration | 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. |
| Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores | Baseline value to 24 hours after first study drug administration | 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. |
| Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores | Baseline value to 48 hours after first study drug administration | 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 to First Rescue Medication | up to 48 hours | The median time to first rescue medication intake (600 mg ibuprofen) in hours. |
| Time to Perceptible Pain Relief | up to 48 hours | 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 to Meaningful Pain Relief | up to 48 hours | 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. |
| Pharmacokinetic Concentrations of Tapentadol | 15 minutes to 20 hours after first drug administration | 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. |
| Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 15 minutes to 20 hours after first drug administration | 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. |
| Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants | Baseline; for the first 6 administrations | 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. |
| Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants | Baseline; for the first 6 administrations | 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. |
| Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores | Baseline value to 48 hours after first study drug administration | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| 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 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 0 |
| Overall Study | Alternative treatment started | 0 | 1 |
| Overall Study | Lack of Efficacy | 7 | 51 |
Baseline characteristics
| Characteristic | Tapentadol Intravenous | Matching Placebo Intravenous | Total |
|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 12.61 | 35.8 years STANDARD_DEVIATION 12.41 | 38.5 years STANDARD_DEVIATION 12.75 |
| Baseline pain intensity | 7.2 units on a scale STANDARD_DEVIATION 1.41 | 7.3 units on a scale STANDARD_DEVIATION 1.54 | 7.2 units on a scale STANDARD_DEVIATION 1.47 |
| Region of Enrollment United States | 64 participants | 65 participants | 129 participants |
| Sex: Female, Male Female | 57 Participants | 60 Participants | 117 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 63 / 64 | 37 / 65 |
| serious Total, serious adverse events | 0 / 64 | 0 / 65 |
Outcome results
Primary
Sum of Pain Intensity Differences (SPID 24)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences (SPID 24) | -51.23 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences (SPID 24) | 25.46 units on a scale |
Secondary
Mean Pain Intensity Scores at Fixed Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | Baseline (before first study drug administration) | 7.2 units on a scale | Standard Deviation 1.41 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 0.25 hours after first dose | 3.7 units on a scale | Standard Deviation 1.99 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 0.5 hour after first dose | 3.1 units on a scale | Standard Deviation 1.77 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 1 hour after first dose | 3.6 units on a scale | Standard Deviation 1.77 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 2 hours after first dose | 5.8 units on a scale | Standard Deviation 2.03 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 4 hours after first dose | 6.1 units on a scale | Standard Deviation 1.92 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 6 hours after first dose | 6.3 units on a scale | Standard Deviation 2.25 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 8 hours after first dose | 6.5 units on a scale | Standard Deviation 2.29 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 12 hours after first dose | 5.2 units on a scale | Standard Deviation 2.7 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 16 hours after first dose | 3.8 units on a scale | Standard Deviation 2.58 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 20 hours after first dose | 3.7 units on a scale | Standard Deviation 2.52 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 24 hours after first dose | 4.1 units on a scale | Standard Deviation 2.43 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 36 hours after first dose | 3.9 units on a scale | Standard Deviation 2.49 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 48 hours after first dose | 4.3 units on a scale | Standard Deviation 2.56 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 20 hours after first dose | 8.0 units on a scale | Standard Deviation 2.24 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | Baseline (before first study drug administration) | 7.3 units on a scale | Standard Deviation 1.54 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 8 hours after first dose | 8.6 units on a scale | Standard Deviation 1.61 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 0.25 hours after first dose | 7.1 units on a scale | Standard Deviation 1.57 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 36 hours after first dose | 8.0 units on a scale | Standard Deviation 2.39 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 0.5 hour after first dose | 7.4 units on a scale | Standard Deviation 1.63 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 12 hours after first dose | 8.5 units on a scale | Standard Deviation 1.67 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 1 hour after first dose | 7.8 units on a scale | Standard Deviation 1.76 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 24 hours after first dose | 8.1 units on a scale | Standard Deviation 2.08 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 2 hours after first dose | 8.5 units on a scale | Standard Deviation 1.5 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 16 hours after first dose | 8.2 units on a scale | Standard Deviation 2.12 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 4 hours after first dose | 8.6 units on a scale | Standard Deviation 1.46 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 48 hours after first dose | 8.1 units on a scale | Standard Deviation 2.21 |
| Matching Placebo Intravenous | Mean Pain Intensity Scores at Fixed Time Points | 6 hours after first dose | 8.7 units on a scale | Standard Deviation 1.47 |
Secondary
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants
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
Population: Participants contributing data (indicated in brackets)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants | prior to second dose | 8.4 units on a scale | Standard Deviation 1.3 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
Secondary
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants
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
Population: Participants contributing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants | prior to second dose | 7.3 units on a scale | Standard Deviation 1.59 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants | prior to third dose | 7.2 units on a scale | Standard Deviation 1.6 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants | prior to fourth dose | 6.6 units on a scale | Standard Deviation 2.21 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants | prior to fifth dose | 4.9 units on a scale | Standard Deviation 2.57 |
| Tapentadol Intravenous | 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 |
| Tapentadol Intravenous | 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
Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores | 27 participants |
| Matching Placebo Intravenous | Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores | 1 participants |
Secondary
Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores | 31 participants |
| Matching Placebo Intravenous | Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores | 4 participants |
Secondary
Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores | 8 participants |
| Matching Placebo Intravenous | Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores | 1 participants |
Secondary
Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores | 18 participants |
| Matching Placebo Intravenous | Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores | 1 participants |
Secondary
Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores | 24 participants |
| Matching Placebo Intravenous | Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores | 1 participants |
Secondary
Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores
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
Population: Full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Intravenous | Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores | 6 participants |
| Matching Placebo Intravenous | Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores | 0 participants |
Secondary
Pain Intensity Differences at Fixed Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 1 hour after first administration | -3.5 units on a scale | Standard Deviation 2.07 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 12 hours after first dose administration | -2.0 units on a scale | Standard Deviation 3.01 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 4 hours after first dose administration | -1.0 units on a scale | Standard Deviation 2.09 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 16 hours after first dose administration | -3.4 units on a scale | Standard Deviation 2.9 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 0.5 hours after first administration | -4.1 units on a scale | Standard Deviation 2.24 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 20 hours after first dose administration | -3.5 units on a scale | Standard Deviation 2.89 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 6 hours after first dose administration | -0.9 units on a scale | Standard Deviation 2.32 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 24 hours after first dose administration | -3.1 units on a scale | Standard Deviation 2.65 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 2 hours after first administration | -1.3 units on a scale | Standard Deviation 2.24 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 36 hours after first dose administration | -3.2 units on a scale | Standard Deviation 2.68 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 8 hours after first dose administration | -0.7 units on a scale | Standard Deviation 2.5 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 48 hours after first dose administration | -2.9 units on a scale | Standard Deviation 2.76 |
| Tapentadol Intravenous | Pain Intensity Differences at Fixed Time Points | 0.25 hours after first administration | -3.5 units on a scale | Standard Deviation 2.22 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 48 hours after first dose administration | 0.8 units on a scale | Standard Deviation 2.11 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 0.25 hours after first administration | -0.2 units on a scale | Standard Deviation 0.95 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 0.5 hours after first administration | 0.1 units on a scale | Standard Deviation 1.18 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 1 hour after first administration | 0.5 units on a scale | Standard Deviation 1.4 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 2 hours after first administration | 1.2 units on a scale | Standard Deviation 1.39 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 4 hours after first dose administration | 1.4 units on a scale | Standard Deviation 1.47 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 6 hours after first dose administration | 1.4 units on a scale | Standard Deviation 1.51 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 8 hours after first dose administration | 1.3 units on a scale | Standard Deviation 1.58 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 12 hours after first dose administration | 1.2 units on a scale | Standard Deviation 1.57 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 16 hours after first dose administration | 0.9 units on a scale | Standard Deviation 1.82 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 20 hours after first dose administration | 0.7 units on a scale | Standard Deviation 2.08 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 24 hours after first dose administration | 0.9 units on a scale | Standard Deviation 2 |
| Matching Placebo Intravenous | Pain Intensity Differences at Fixed Time Points | 36 hours after first dose administration | 0.8 units on a scale | Standard Deviation 2.26 |
Secondary
Patient Global Impression of Change After 12 Hours of Treatment
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
Population: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Much Improved | 20 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Minimally Worse | 4 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Minimally Improved | 14 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Much Worse | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Very Much Improved | 11 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Very Much Worse | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | No Change | 5 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Very Much Worse | 0 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Very Much Improved | 0 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Minimally Improved | 9 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | No Change | 4 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Minimally Worse | 1 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Much Worse | 0 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 12 Hours of Treatment | Much Improved | 1 participants |
Secondary
Patient Global Impression of Change After 48 Hours of Treatment
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
Population: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Minimally Improved | 4 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Minimally Worse | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Much Improved | 24 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Much Worse | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | No Change | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Very Much Worse | 0 participants |
| Tapentadol Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Very Much Improved | 19 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Very Much Worse | 0 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Very Much Improved | 2 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Much Improved | 8 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Minimally Improved | 2 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | No Change | 1 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Minimally Worse | 0 participants |
| Matching Placebo Intravenous | Patient Global Impression of Change After 48 Hours of Treatment | Much Worse | 0 participants |
Secondary
Patients Global Impression of Change After 24 Hours of Treatment
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
Population: Participants contributing data. Missing PGIC values were mainly due to participants discontinuing the trial before this time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Much Improved | 26 participants |
| Tapentadol Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | No Change | 1 participants |
| Tapentadol Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Minimally Improved | 11 participants |
| Tapentadol Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Minimally Worse | 1 participants |
| Tapentadol Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Very Much Improved | 13 participants |
| Matching Placebo Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Minimally Worse | 2 participants |
| Matching Placebo Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Very Much Improved | 0 participants |
| Matching Placebo Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Much Improved | 5 participants |
| Matching Placebo Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | Minimally Improved | 6 participants |
| Matching Placebo Intravenous | Patients Global Impression of Change After 24 Hours of Treatment | No Change | 2 participants |
Secondary
Pharmacokinetic Concentrations of Tapentadol
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 3.5 hours after end of fifth infusion | 73.2 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 15 minutes after first infusion | 201.2 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 30 minutes after first infusion | 99.5 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 60 minutes after first infusion | 76.4 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 4 hours after end of first infusion | 38.2 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol | 4 hours after end of fifth infusion | 70.3 ng/mL |
Secondary
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 15 minutes after first infusion | 26.4 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 30 minutes after first infusion | 290.4 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 60 minutes after first infusion | 488.2 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 4 hours after end of first infusion | 452.4 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 3.5 hours after end of fifth infusion | 1048.7 ng/mL |
| Tapentadol Intravenous | Pharmacokinetic Concentrations of Tapentadol-O-glucuronide | 4 hours after end of fifth infusion | 945.1 ng/mL |
Secondary
Sum of Pain Intensity Differences After 12 Hours
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
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences After 12 Hours | -14.98 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences After 12 Hours | 14.82 units on a scale |
Secondary
Sum of Pain Intensity Differences After 48 Hours
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
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences After 48 Hours | -122.93 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences After 48 Hours | 45.86 units on a scale |
Secondary
Sum of Pain Intensity Differences After 4 Hours
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences After 4 Hours | -6.76 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences After 4 Hours | 4.22 units on a scale |
Secondary
Sum of Pain Intensity Differences After 60 Minutes
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
Population: Full analysis set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences After 60 Minutes | -3.65 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences After 60 Minutes | 0.26 units on a scale |
Secondary
Sum of Pain Intensity Differences After 8 Hours
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
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Intravenous | Sum of Pain Intensity Differences After 8 Hours | -9.9 units on a scale |
| Matching Placebo Intravenous | Sum of Pain Intensity Differences After 8 Hours | 9.74 units on a scale |
Secondary
Time to First Rescue Medication
The median time to first rescue medication intake (600 mg ibuprofen) in hours.
Time frame: up to 48 hours
Population: Full analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tapentadol Intravenous | Time to First Rescue Medication | 5.4 hours |
| Matching Placebo Intravenous | Time to First Rescue Medication | 2.1 hours |
Secondary
Time to Meaningful Pain Relief
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Tapentadol Intravenous | Time to Meaningful Pain Relief | 0.3 hours |
Secondary
Time to Perceptible Pain Relief
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Tapentadol Intravenous | Time to Perceptible Pain Relief | 0.2 hours |
Post Hoc
Number of Participants Scored as a Responder Based on Patient Global Impression of Change
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 12 hours after first dose | 31 participants |
| Tapentadol Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 24 hours after first dose | 39 participants |
| Tapentadol Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 48 hours after first dose | 43 participants |
| Matching Placebo Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 12 hours after first dose | 1 participants |
| Matching Placebo Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 24 hours after first dose | 5 participants |
| Matching Placebo Intravenous | Number of Participants Scored as a Responder Based on Patient Global Impression of Change | Responders 48 hours after first dose | 10 participants |