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Trial record 1 of 1 for:    NCT01352741
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Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin

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ClinicalTrials.gov Identifier: NCT01352741
Recruitment Status : Completed
First Posted : May 12, 2011
Results First Posted : August 12, 2016
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Low Back Pain
Neuropathic Pain
Interventions Drug: Tapentadol Prolonged Release
Drug: Tapentadol Prolonged Release with Pregabalin
Drug: Tapentadol Prolonged Release open label maintenance
Enrollment 622
Recruitment Details The trial started on 23 Mar 2011 and the last participant completed the last follow-up examination on the 17 Jan 2012.
Pre-assignment Details

622 participants signed an informed consent. All participants included in the 8 week Double Blind Comparative Period were initially in the open-label titration period.

Participants in the open-label tapentadol continuation period were in the open-label titration period but did not enter the comparative period.

Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description All participants entered the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion. Participants that did not qualify for entry into the Comparative Period were able to enter the open-label Continuation Period. During the double-blind comparator phase the dose was increased to 200 mg twice daily and after a week to 250 mg twice daily. Participants that dropped out due to tolerability issues during the comparative period were able to enter the open-label pick-up arm. At the end of the Open-label Tapentadol Titration Period participants that qualified were randomized to either tapentadol or tapentadol and pregabalin treatment. In this double-blind period participants started on Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.
Period Title: Open-label Tapentadol Titration Period
Started 445 [1] 0
Switched to Open-label Continuation Arm 59 0
Full Analysis Set 436 0
Completed 372 [2] 0
Not Completed 73 0
Reason Not Completed
Protocol Violation             4             0
Lack of Efficacy             19             0
Adverse Event             34             0
Withdrawal of consent             7             0
Non-compliance with Trial Requirements             5             0
Other             4             0
[1]
All participants started with 2 x 50 mg tapentadol PR and titrated upwards in steps of 100 mg/day.
[2]
59 of 73 participants not completing the titration period entered the open-label continuation arm.
Period Title: Double-blind Comparative Period
Started 154 [1] 159 [2]
Switched to Open-label Pick-up Arm 19 18
No Pain Assessments Available 2 2
Full Analysis Set 152 157
Major Protocol Deviations 13 8
Per Protocol Set 139 149
painDetect Per Protocol Set 109 127
SF-12 Per Protocol Set 131 143
EQ-5D Per Protocol Set 131 143
HADS Per Protocol Set (PPS) 123 137
Sleep Evaluation (Latency) PPS 123 137
Sleep Evaluations (Awakenings) PPS 123 137
Sleep Evaluations (Hours Slept) PPS 123 137
Completed 126 133
Not Completed 28 26
Reason Not Completed
Protocol Violation             2             0
Lack of Efficacy             0             3
Adverse Event             16             17
Lost to Follow-up             1             0
Death             0             1
Withdrawal of consent             8             3
Other             1             2
[1]
Of the 313 participants that qualified for randomization 154 were randomized to tapentadol.
[2]
159 of the 313 participants that qualified were randomized to tapentadol and pregabalin treatment.
Period Title: Open-Label Tapentadol Continuation Arm
Started 59 [1] 0 [2]
Major Protocol Deviation 2 0
Full Analysis Set 57 0
Completed 51 0
Not Completed 8 0
Reason Not Completed
Adverse Event             4             0
Lack of Efficacy             1             0
Withdrawal by Subject             2             0
Protocol Violation             1             0
[1]
59 of the 73 participants that did not qualify for the comparative period entered this arm.
[2]
In this period no tapentadol PR and pregabalin treatment was planned by the protocol.
Period Title: Open-Label Tapentadol Pick-Up Arm
Started 37 [1] 0 [2]
Completed 37 0
Not Completed 0 0
[1]
19 from tapentadol in the comparative phase and 18 from tapentadol & pregabalin entered this arm.
[2]
Participants did not continue treatment. They were switched to tapentadol PR or discontinued.
Arm/Group Title All Trial Participants
Hide Arm/Group Description All participants that received at least one dose of tapentadol prolonged release at baseline, in the open-label titration period.
Overall Number of Baseline Participants 445
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 445 participants
57.9  (11.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 445 participants
Female
262
  58.9%
Male
183
  41.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 445 participants
White 441
Asian 2
Other 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 445 participants
Spain 54
Belgium 45
Poland 102
Denmark 41
Austria 55
Netherlands 26
Germany 122
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 445 participants
168.2  (9.97)
[1]
Measure Description: Data available for 441 participants
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 445 participants
83.61  (17.542)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m²
Number Analyzed 445 participants
29.57  (5.616)
[1]
Measure Description: Data available for 441 participants.
Diagnosis of Lumbar Radiculopathy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 445 participants
Yes 310
No 134
Missing 1
[1]
Measure Description: Number of participants with dermatomal pain present as assessed by the investigator. For a participant to have diagnosed lumbar radiculopathy pain, they must have answered 'yes' to all three dermatomal pain questions and 'yes' to at least one of the three root dysfunction questions
History of low back pain   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 445 participants
6.3
(2.1 to 11.7)
[1]
Measure Description: Participants were asked since when they suffer from their current pain.
Subject's satisfaction with previous treatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 445 participants
Poor 126
Fair 233
Good 68
Very Good 10
Excellent 1
Missing 7
1.Primary Outcome
Title Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Hide Description

The primary endpoint is defined as the comparison of tapentadol prolonged release (PR) 300 mg plus 200 mg per day and the combination of tapentadol PR 300 mg per day and pregabalin 300 mg per day regarding the change in NRS-3 pain intensity scores (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) from the randomization visit to the final evaluation visit.

Theoretically a maximum decrease of -10 and an increase of +4 in the pain intensity would have been possible. A negative sign indicates a decrease in pain intensity from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline visit).

Time Frame Randomization (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.6  (2.52) -1.7  (2.48)
2.Secondary Outcome
Title Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Hide Description The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine. This is the treatment period prior to the primary outcome period.
Time Frame Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed values.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily. Tapentadol PR was administered in an open-label fashion during the 3-week titration period. All participants started at 2 x 50 mg (100 mg per day) after the baseline visit and titrated upwards on a weekly basis by 2 x 50 mg. Dose adjustment could have taken place after 3 days on a stable dose if the participant's pain required faster titration.
Overall Number of Participants Analyzed 445
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=438) 7.2  (1.21)
Baseline Visit (N=440) 8.3  (1.14)
Randomization Visit (N=377) 5.4  (1.83)
3.Secondary Outcome
Title Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Hide Description The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Time Frame Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed values.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Participants that did not qualify for randomization to the Comparator Period, continued on a stable dose of Tapentadol Prolonged Release 300 mg per day, if they had reached a satisfactory level of pain relief.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=56) 7.3  (1.30)
Baseline Visit (N=57) 7.9  (1.23)
Randomization Visit (N=57) 2.6  (1.27)
Final Evaluation Visit (N=59) 2.6  (2.09)
4.Secondary Outcome
Title End of Open-label Pick-up Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Hide Description The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Time Frame Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Tapentadol Prolonged Release After Tapentadol Tapentadol Prolonged Release After Tapentadol and Pregabalin
Hide Arm/Group Description:
Participants that drop-out of the double-blind tapentadol prolonged release treatment in the Comparative Period, due to tolerability issues, continued on Tapentadol Prolonged Release at either 300 mg per day or 400 mg per day in this Open-Label Pick-up arm.
Participants that dropped-out of the Tapentadol Prolonged Release and Pregabalin in the double-blind Comparative Period continued with Tapentadol Prolonged Release at either 300 or 400 mg per day in this Open-Label Pick-up arm.
Overall Number of Participants Analyzed 19 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.4  (2.83) 4.5  (1.96)
5.Secondary Outcome
Title Open-label Titration Period: Radiating Pain
Hide Description The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Time Frame Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily. Tapentadol PR was administered in an open-label fashion during the 3-week titration period. All participants started at 2 x 50 mg (100 mg per day) after the baseline visit and titrated upwards on a weekly basis by 2 x 50 mg. Dose adjustment could have taken place after 3 days on a stable dose if the participant's pain required faster titration
Overall Number of Participants Analyzed 445
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=438) 7.0  (1.64)
Baseline Visit (N=440) 8.0  (1.60)
Randomization Visit (N=377) 5.3  (2.16)
6.Secondary Outcome
Title Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population
Hide Description The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Time Frame Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 7.1  (1.75) 6.9  (1.49)
Baseline Visit (N=139; N=149) 8.1  (1.84) 8.1  (1.37)
Randomization Visit (N=139; N=149) 5.6  (1.87) 5.7  (1.86)
7.Secondary Outcome
Title Double-blind Comparative Period: Change in NRS-3 Pain Intensity Score for the Radiating Pain
Hide Description

NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot).

The value reported represents the change from the randomization visit (i.e., the last 3 days in the titration period) to the end of the double-blind comparative period (i.e., the last 3 days in the comparative period). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (baseline visit).

Time Frame Randomization Visit (Day 22); End of Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.5  (2.61) -1.9  (2.60)
8.Secondary Outcome
Title Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours
Hide Description

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.

The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".

Time Frame Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily. Tapentadol PR was administered in an open-label fashion during the 3-week titration period. All participants started at 2 x 50 mg (100 mg per day) after the baseline visit and titrated upwards on a weekly basis by 2 x 50 mg. Dose adjustment could have taken place after 3 days on a stable dose if the participant's pain required faster titration.
Overall Number of Participants Analyzed 445
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=438) 7.6  (1.32)
Baseline Visit (N=440) 8.5  (1.11)
Randomization Visit (N=377) 5.8  (1.98)
9.Secondary Outcome
Title Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours
Hide Description

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric Rating Scale (NRS), where 0 = "no pain" and 10 = "pain as bad as you can imagine".

The participant was asked : "Please rate your pain intensity by assessing the one number that best describes your worst pain during the past 24 hours prior to the visit".

Time Frame Enrollment Visit (Day-12); Baseline Visit (day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS)
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 7.8  (1.21) 7.5  (1.27)
Baseline Visit (N=139; N=149) 8.5  (1.07) 8.7  (0.97)
Randomization Visit (N=139; N=149) 6.3  (1.52) 6.4  (1.4)
10.Secondary Outcome
Title Double-blind Comparative Period: Change in Worst Pain Intensity Over the Past 24 Hours
Hide Description

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.

The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".

A negative change indicates that the pain intensity decreased from the start of the trial.

Time Frame Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.7  (2.67) -1.8  (2.58)
11.Secondary Outcome
Title Open-label Titration Period: painDETECT Assessments
Hide Description The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".
Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily. Tapentadol PR was administered in an open-label fashion during the 3-week titration period. All participants started at 2 x 50 mg (100 mg per day) after the baseline visit and titrated upwards on a weekly basis by 2 x 50 mg. Dose adjustment could have taken place after 3 days on a stable dose if the participant's pain required faster titration.
Overall Number of Participants Analyzed 445
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=438) 21.4  (5.46)
Baseline Visit (N=440) 22.7  (5.74)
Randomization Visit (N=377) 16.9  (6.57)
12.Secondary Outcome
Title Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment
Hide Description The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".
Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 21.6  (5.23) 21.7  (5.17)
Baseline Visit (N=139; N=149) 22.4  (5.21) 23.8  (5.51)
Randomization Visit (N=138; N=149) 17.6  (5.93) 18.4  (5.90)
13.Secondary Outcome
Title Double-blind Comparative Period: Change in painDETECT Final Assessment
Hide Description The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear". The theoretical range of change in this trial ranged from -38 to 19. A negative change indicated a decrease in their neuropathic component of pain.
Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 109 127
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline -10.2  (8.57) -11.0  (7.73)
Change from Randomization -6.0  (8.99) -5.9  (7.22)
14.Secondary Outcome
Title Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment
Hide Description In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.
Time Frame Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Tapentadol Prolonged Release
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily. Tapentadol PR was administered in an open-label fashion during the 3-week titration period. All participants started at 2 x 50 mg (100 mg per day) after the baseline visit and titrated upwards on a weekly basis by 2 x 50 mg. Dose adjustment could have taken place after 3 days on a stable dose if the participant's pain required faster titration.
Overall Number of Participants Analyzed 445
Mean (Standard Deviation)
Unit of Measure: units on a scale
Overall Score Enrollment Visit (N=438) 55.2  (16.86)
Overall Score Baseline Visit (N=440) 62.7  (18.41)
Overall Score Randomization Visit (N=377) 42.0  (20.29)
15.Secondary Outcome
Title Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population
Hide Description In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.
Time Frame Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Overall Score Enrollment Visit (N=138, N=149) 54.8  (15.12) 57.6  (16.07)
Overall Score Baseline Visit (N=139, N=149) 62.8  (17.13) 65.4  (18.29)
Overall Score Randomization Visit (N=139, N=149) 45.2  (17.99) 46.5  (18.57)
Overall Score Final Evaluation Visit(N=131, N=143) 28.9  (21.78) 30.5  (22.38)
16.Secondary Outcome
Title Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment
Hide Description In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale, from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. Spontaneous Pressing Pain Subscore). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) subscores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 10 (100 for the overall score) . A negative change indicates that the intensity of the symptom has decreased since the start of treatment.
Time Frame Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 131 143
Mean (Standard Deviation)
Unit of Measure: units on a scale
Overall Score -16.8  (18.95) -16.6  (20.04)
Subscore: Superficial Spontaneous Burning -1.9  (2.75) -2.3  (2.65)
Subscore: Deep Sponatenous Pressing Pain -1.4  (2.26) -1.4  (2.58)
Subscore: Paroxysmal Pain -2.0  (2.39) -1.6  (2.44)
Subscore: Evoked Pain -1.8  (2.28) -1.7  (2.32)
Subscore: Parasthesia/Dysesthesia -1.4  (2.44) -1.5  (2.49)
17.Secondary Outcome
Title Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
Hide Description The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.
Time Frame Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 29.9  (8.55) 29.8  (7.56)
Baseline Visit (N=139; N=149) 28.2  (8.17) 28.5  (7.68)
Randomization Visit (N=139; N=149) 34.1  (9.36) 34.1  (8.45)
18.Secondary Outcome
Title Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
Hide Description

The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical summary scores were calculated from the individual responses to those questions covering physical health. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.

The change in the SF-12 score shows an improvement in health from baseline if the values are positive. The higher the value the greater the improvement.

Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 131 143
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline Visit 12.3  (12.98) 11.1  (11.36)
Change from Randomization Visit 6.2  (13.04) 5.6  (10.88)
19.Secondary Outcome
Title Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
Hide Description The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.
Time Frame Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 46.1  (11.84) 44.8  (12.24)
Baseline Visit (N=139; N=149) 45.4  (12.43) 43.2  (13.32)
Randomization Visit (N=139; N=149) 49.2  (11.64) 47.3  (11.80)
20.Secondary Outcome
Title Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
Hide Description The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.
Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 131 143
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline Visit (N=131; N=143) 3.9  (10.59) 6.5  (11.62)
Change from Randomization Visit (N=131; N=143) 0.1  (8.42) 2.5  (9.77)
21.Secondary Outcome
Title Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population
Hide Description The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Time Frame Enrollment Visit (day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 0.32  (0.304) 0.33  (0.313)
Baseline Visit (N=139; N=149) 0.29  (0.306) 0.18  (0.316)
Randomization Visit (N=139; N=149) 0.55  (0.254) 0.52  (0.237)
22.Secondary Outcome
Title Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index
Hide Description The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 131 143
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline Visit 0.34  (0.358) 0.43  (0.386)
Change from Randomization Visit 0.09  (0.317) 0.09  (0.254)
23.Secondary Outcome
Title Double-blind Comparative Period: Patient Global Impression of Change (PGIC)
Hide Description In the Patient Global Impression of Change (PGIC) the participant indicated the perceived change over the treatment period. PGIC is a 7 point scale where the patient's rates overall improvement. Patients rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Time Frame Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind comparative population. Full Analysis Set (FAS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 152 157
Measure Type: Number
Unit of Measure: participants
Very much improved 28 32
Much improved 44 66
Minimally improved 51 31
No change 10 10
Minimally worse 5 5
Much worse 4 5
Very much worse 0 1
Missing 10 7
24.Secondary Outcome
Title Double-blind Comparative Period: Clinician Global Impression of Change (CGIC)
Hide Description In the Clinician Global Impression of Change (CGIC) the clinician indicated the perceived change over the treatment period. The clinician was requested to choose one of seven categories for each participant. The Clinician rated the participants change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Time Frame Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Full Analysis Set (FAS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 142 150
Measure Type: Number
Unit of Measure: participants
Very much improved 26 30
Much improved 54 82
Minimally improved 46 19
No change 8 10
Minimally worse 3 2
Much worse 5 5
Very much worse 0 2
Missing 10 7
25.Secondary Outcome
Title Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
Hide Description

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.

A decrease in values over the trial period indicate that there has been an improvement.

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 7.4  (4.51) 8.6  (4.94)
Baseline Visit (N=139; N=149) 7.7  (4.52) 9.0  (5.15)
Randomization Visit (N=139; N=149) 5.8  (3.77) 7.1  (4.39)
26.Secondary Outcome
Title Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
Hide Description

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.

A negative sign indicates that there has been a decrease in anxiety since the start of treatment.

Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 123 137
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline Visit -2.2  (3.70) -3.1  (4.28)
Change from Randomization Visit -0.3  (2.93) -1.2  (3.38)
27.Secondary Outcome
Title Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
Hide Description The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement.
Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind Comparative Population; Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
Enrollment Visit (N=138; N=149) 6.9  (4.18) 7.8  (4.43)
Baseline Visit (N=139; N=149) 7.6  (4.66) 8.6  (4.81)
Randomization Visit (N=139; N=149) 6.0  (3.96) 6.8  (4.24)
28.Secondary Outcome
Title Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
Hide Description The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. A negative change value indicates a decrease in the depression score since the start of treatment.
Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 123 137
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from Baseline Visit -2.0  (3.56) -3.1  (3.99)
Change from Randomization Visit -0.4  (3.06) -1.3  (2.94)
29.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Latency
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the sleep latency.

To assess latency the participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]?

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Enrollment Visit (Day -12) Baseline Visit (Day 1) Randomization Visit (Day 22)
Hide Arm/Group Description:
Participant feedback at the Enrollment Visit; on previous analgesic medication prior to study drug start.
At the end of the washout period prior to starting 100 mg/day tapentadol prolonged release.
End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Overall Number of Participants Analyzed 438 440 377
Mean (Standard Deviation)
Unit of Measure: hours
1.2  (1.50) 1.5  (1.56) 1.3  (1.67)
30.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population
Hide Description The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the Randomization Visit (Baseline) and for the night prior to the Final Evaluation Visit (12 weeks after randomization). The higher the value the longer it took to fall asleep. Sleep evaluation questionnaire (SQ) items
Time Frame Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: hours
Enrollment Visit (N=138, N=149) 1.3  (1.70) 1.3  (1.52)
Baseline Visit (N=139, N=149) 1.5  (1.65) 1.5  (1.54)
Randomization Visit (N=139, N=149) 1.1  (1.45) 1.4  (1.78)
31.Secondary Outcome
Title Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency
Hide Description The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the visits. The negative change from baseline indicates that the time to falling asleep decreased from baseline in a treatment group.
Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 123 137
Mean (Standard Deviation)
Unit of Measure: hours
Change from baseline visit -0.3  (2.30) -0.3  (2.10)
Change from randomization visit 0.2  (1.88) -0.2  (2.04)
32.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Awakenings
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).

The participant was asked at each visit: "How many times did you wake up during the night?"

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Observed.
Arm/Group Title Enrollment Visit (Day -12) Baseline Visit (Day 1) Randomization Visit (Day 22)
Hide Arm/Group Description:
Participant feedback at the Enrollment Visit; on previous analgesic medication prior to study drug start.
At the end of the washout period prior to starting 100 mg/day tapentadol prolonged release.
End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Overall Number of Participants Analyzed 438 440 377
Mean (Standard Deviation)
Unit of Measure: Number of Awakenings
3.3  (2.64) 3.9  (3.11) 2.5  (1.87)
33.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).

The participant was asked at each visit: "How many times did you wake up during the night?"

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
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Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
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Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: Number of Awakenings
Enrollment Visit (N=138; N=149) 3.2  (2.84) 3.4  (2.36)
Baseline Visit (N=139; N=149) 3.6  (2.47) 4.6  (4.01)
Randomization Visit (N=139; N=149) 2.5  (1.76) 2.7  (2.00)
34.Secondary Outcome
Title Double-blind Comparative Period: Change in the Number of Awakenings
Hide Description The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings. Participants were asked: How many times did you wake up during the night? The change in the Number of Awakenings was calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Final Evaluation Visit (Day 77). A negative change indicates that the number of awakenings in a treatment group have gone down since the Baseline or Randomization Visit. In general pain can interfere with sleep, one potential indicator is the number of awakenings.
Time Frame Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
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Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 123 137
Mean (Standard Deviation)
Unit of Measure: Number of Awakenings
Change from Baseline Visit -1.4  (2.57) -2.5  (3.11)
Change from Randomization Visit -0.2  (2.01) -0.8  (1.78)
35.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Time Slept
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The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

The participant was asked: "How long did you sleep last night?" [Answered in hours and minutes].

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
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Observed.
Arm/Group Title Enrollment Visit (Day -12) Baseline Visit (Day 1) Randomization Visit (Day 22)
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Participant feedback at the Enrollment Visit; on previous analgesic medication prior to study drug start.
At the end of the washout period prior to starting 100 mg/day tapentadol prolonged release.
End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Overall Number of Participants Analyzed 438 440 377
Mean (Standard Deviation)
Unit of Measure: hours
5.8  (1.69) 5.3  (1.79) 6.4  (1.41)
36.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population
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The participants were requested to answer the following question:

How long did you sleep last night [hours]? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization).

Time Frame Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Mean (Standard Deviation)
Unit of Measure: hours
Enrollment Visit (N=138, N=149) 5.8  (1.66) 5.7  (1.70)
Baseline Visit (N=139, N=149) 5.3  (1.67) 5.2  (1.70)
Randomization Visit (N=139, N=149) 6.2  (1.30) 6.4  (1.59)
37.Secondary Outcome
Title Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept
Hide Description The sleep evaluation questionnaire was completed by the participant. The answer was in response to the question: Sleep evaluation: How long did you sleep last night [hours]? The value reported is the change in the number of hours of sleep from baseline. The positive value indicates that there was an increase in the number of hours of sleep in a treatment group.
Time Frame Baseline Visit (Day -12); Randomization Visit (Day 1); Final Evaluation Visit (Day 77)
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Per Protocol Set.
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 123 137
Mean (Standard Deviation)
Unit of Measure: hours
Change from baseline visit 1.2  (1.89) 1.6  (1.84)
Change from randomization visit 0.3  (1.71) 0.3  (1.70)
38.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep
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The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Time Frame Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
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Observed.
Arm/Group Title Enrollment Visit (Day -12) Baseline Visit (Day 1) Randomization Visit (Day 22)
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Participant feedback at the Enrollment Visit; on previous analgesic medication prior to study drug start.
At the end of the washout period prior to starting 100 mg/day tapentadol prolonged release.
End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Overall Number of Participants Analyzed 445 445 445
Measure Type: Number
Unit of Measure: participants
Excellent 9 5 21
Good 110 76 173
Fair 171 149 127
Poor 148 210 56
Missing 7 5 68
39.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Time Frame Enrollment Visit (Day-12)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Measure Type: Number
Unit of Measure: participants
Excellent 1 5
Good 37 30
Fair 42 61
Poor 58 53
Missing 1 0
40.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Time Frame Baseline Visit (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Measure Type: Number
Unit of Measure: participants
Excellent 2 1
Good 23 17
Fair 42 49
Poor 72 82
41.Secondary Outcome
Title Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Hide Description

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Time Frame Randomization Visit (Day 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Measure Type: Number
Unit of Measure: participants
Excellent 7 8
Good 62 59
Fair 48 56
Poor 22 26
42.Secondary Outcome
Title Double-blind Comparative Period: Change in the Overall Quality of Sleep
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The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The improvement, no change or worsening is reported based on the replies scored by the participants given at their End of Continuation Visit.

Time Frame Randomization Visit (Day 22) to Final Evaluation (Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Comparative Population. Per Protocol Set (PPS).
Arm/Group Title Tapentadol Prolonged Release Tapentadol Prolonged Release and Pregabalin
Hide Arm/Group Description:
Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.
Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.
Overall Number of Participants Analyzed 139 149
Measure Type: Number
Unit of Measure: participants
Improvement 39 58
No change 63 59
Worsening 21 20
Missing 16 12
43.Secondary Outcome
Title Open-label Titration Period: Subject's Satisfaction With Treatment
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Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:

"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.

Time Frame End of Open-label Titration Period at Randomization Visit (Day 22)
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Last Observation Carried Forward (LOCF); Per Protocol Set
Arm/Group Title Tapentadol Prolonged Release
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Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period.
Overall Number of Participants Analyzed 445
Measure Type: Number
Unit of Measure: participants
Poor 12
Fair 119
Good 178
Very Good 58
Excellent 11
Missing 67
44.Secondary Outcome
Title Double-blind Comparative Period: Subject's Satisfaction With Treatment
Hide Description

Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:

"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.

Time Frame End of Comparative Period at Final Evaluation Visit (Day 77)
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Last Observation Carried Forward (LOCF); Per Protocol Set
Arm/Group Title Tapentadol in the Comparative Period Tapentadol and Pregabalin in the Comparative Period
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The dose of Tapentadol Prolonged Release was increased to 400 mg (2 x 200mg) and a week later to 500 mg (2 x 250 mg) per day and maintained at 500 mg per day.
Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.
Overall Number of Participants Analyzed 139 149
Measure Type: Number
Unit of Measure: participants
Poor 3 6
Fair 32 28
Good 43 43
Very Good 32 43
Excellent 21 23
Missing 8 6
Time Frame Baseline Visit; up to end of Week 11.
Adverse Event Reporting Description

Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit.

One participant died, before the baseline visit, during the washout phase of the clinical trial.

 
Arm/Group Title Open-Label Tapentadol Titration Period Tapentadol in the Comparative Period Tapentadol and Pregabalin in the Comparative Period Open-Label Tapentadol Pick-Up Arm Open-Label Tapentadol Continuation Period
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During the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion.

Titration dose steps on a weekly basis:

First 50 mg administered twice daily, then 100 mg administered twice daily and then 150 mg administered twice daily.

The titration period could be shortened to 10 days, with a participant at a predefined dose level for at least 3 days.

The dose of 300 mg Tapentadol per day was maintained until the Randomization Visit.

The dose of Tapentadol Prolonged Release was increased to 400 mg (2 x 200mg) and a week later to 500 mg (2 x 250 mg) per day and maintained at 500 mg per day. Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day. Participants that drop-out of the Comparative Period, due to tolerability issues, were permitted to continue on Tapentadol Prolonged Release at either 300 mg per day or 400 mg per day. Participants who did not qualify for randomization to the Comparator Period, continued on a stable dose of Tapentadol Prolonged Release 300 mg per day if they had reached a satisfactory level of pain relief.
All-Cause Mortality
Open-Label Tapentadol Titration Period Tapentadol in the Comparative Period Tapentadol and Pregabalin in the Comparative Period Open-Label Tapentadol Pick-Up Arm Open-Label Tapentadol Continuation Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Open-Label Tapentadol Titration Period Tapentadol in the Comparative Period Tapentadol and Pregabalin in the Comparative Period Open-Label Tapentadol Pick-Up Arm Open-Label Tapentadol Continuation Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/445 (0.67%)   5/154 (3.25%)   3/159 (1.89%)   2/37 (5.41%)   2/59 (3.39%) 
Cardiac disorders           
Cardiac arrest  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Cardiac failure  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Tachycardia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Ear and labyrinth disorders           
Vertigo  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Endocrine disorders           
Goitre  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Abdominal pain upper  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Constipation  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nausea  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
General disorders           
Chest pain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Device dislocation  1 [1]  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Drug withdrawal syndrome  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Injury, poisoning and procedural complications           
Chest injury  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Fall  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Musculoskeletal and connective tissue disorders           
Flank pain  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nervous system disorders           
Muscle contractions involuntary  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pulmonary embolism  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Skin and subcutaneous tissue disorders           
Hyperhidrosis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Vascular disorders           
Thrombosis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
[1]
Luxation of new implanted total endoprosthesis left hip
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Open-Label Tapentadol Titration Period Tapentadol in the Comparative Period Tapentadol and Pregabalin in the Comparative Period Open-Label Tapentadol Pick-Up Arm Open-Label Tapentadol Continuation Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   227/445 (51.01%)   98/154 (63.64%)   103/159 (64.78%)   37/37 (100.00%)   36/59 (61.02%) 
Blood and lymphatic system disorders           
Anaemia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Cardiac disorders           
Atrial Fibrillation  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Brachycardia  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Cardiac Failure  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Cardiovascular Disorder  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Palpitation  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Ear and labyrinth disorders           
Cupulolithiasis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Ear Discomfort  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Ear pain  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
External Ear Disorder  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Inner Ear Disorder  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Motion Sickness  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Tinnitus  1  1/445 (0.22%)  1/154 (0.65%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Vertigo  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Eye disorders           
Accommodation Disorder  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Atrial Fibrillation  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Dry Eye  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Eye Irritation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Eye pruritis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Vision Blurred  1  1/445 (0.22%)  2/154 (1.30%)  0/159 (0.00%)  3/37 (8.11%)  0/59 (0.00%) 
Visual Acuity Reduced  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Visual Impairment  1  0/445 (0.00%)  1/154 (0.65%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Gastrointestinal disorders           
Abdominal Discomfort  1  2/445 (0.45%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Abdominal Distension  1  2/445 (0.45%)  0/154 (0.00%)  2/159 (1.26%)  2/37 (5.41%)  0/59 (0.00%) 
Abdominal Pain  1  3/445 (0.67%)  2/154 (1.30%)  0/159 (0.00%)  1/37 (2.70%)  1/59 (1.69%) 
Abdominal Pain Lower  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Abdominal Pain Upper  1  7/445 (1.57%)  2/154 (1.30%)  2/159 (1.26%)  1/37 (2.70%)  1/59 (1.69%) 
Abdominal Symptom  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Abnormal Faeces  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Colitis  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Colonic Polyp  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Constipation * 1  25/445 (5.62%)  11/154 (7.14%)  8/159 (5.03%)  9/37 (24.32%)  10/59 (16.95%) 
Diarrhoea  1  14/445 (3.15%)  6/154 (3.90%)  3/159 (1.89%)  3/37 (8.11%)  2/59 (3.39%) 
Dry Mouth  1  35/445 (7.87%)  6/154 (3.90%)  8/159 (5.03%)  6/37 (16.22%)  6/59 (10.17%) 
Dyspepsia  1  6/445 (1.35%)  1/154 (0.65%)  2/159 (1.26%)  1/37 (2.70%)  1/59 (1.69%) 
Dysphagia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Enteritis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Faeces hard  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Flatuence  1  2/445 (0.45%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Frequent Bowel Movements  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Gastritis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Gastrointestinal Disorder  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Glossodynia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Haematochezia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Haemorrhoids  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Hyperchlorhydria  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Inflammatory Bowel Disease  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Nausea  1  58/445 (13.03%)  16/154 (10.39%)  14/159 (8.81%)  12/37 (32.43%)  11/59 (18.64%) 
Oesophagitis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Uvulitis  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Vomiting  1  20/445 (4.49%)  9/154 (5.84%)  5/159 (3.14%)  5/37 (13.51%)  4/59 (6.78%) 
General disorders           
Asthenia  1  6/445 (1.35%)  4/154 (2.60%)  0/159 (0.00%)  2/37 (5.41%)  2/59 (3.39%) 
Chest Discomfort  1  2/445 (0.45%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Chills  1  2/445 (0.45%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Discomfort  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Drug Withdrawal Syndrome  1  2/445 (0.45%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  1/59 (1.69%) 
Fatigue  1  25/445 (5.62%)  13/154 (8.44%)  16/159 (10.06%)  10/37 (27.03%)  5/59 (8.47%) 
Feeling Abnormal  1  2/445 (0.45%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Feeling Cold  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Feeling Drunk  1  1/445 (0.22%)  1/154 (0.65%)  2/159 (1.26%)  1/37 (2.70%)  0/59 (0.00%) 
Feeling Hot  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Gait Disturbance  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Generalised Oedema  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Hyperplasia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Inflammation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Influenza Like Illness  1  4/445 (0.90%)  2/154 (1.30%)  3/159 (1.89%)  1/37 (2.70%)  0/59 (0.00%) 
Irritability  1  3/445 (0.67%)  0/154 (0.00%)  3/159 (1.89%)  0/37 (0.00%)  0/59 (0.00%) 
Malaise  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Oedema Peripheral  1  6/445 (1.35%)  0/154 (0.00%)  3/159 (1.89%)  0/37 (0.00%)  1/59 (1.69%) 
Pain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Pyrexia  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Thirst  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Immune system disorders           
Seasonal Allergy  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Infections and infestations           
Abdominal Abscess  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Acute Tonsillitis  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Bacterial Infection  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Bronchitis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Cystitis  1  0/445 (0.00%)  2/154 (1.30%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Diverticulitis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Ear Infection  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Gastroenteritis  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  1/59 (1.69%) 
Gastroenteritis Viral  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Gastrointestinal Infection  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Herpes Zoster Oticus  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Infection  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Influenza  1  0/445 (0.00%)  2/154 (1.30%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Laryngitis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Localised Infection  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Nasopharyngitis  1  7/445 (1.57%)  2/154 (1.30%)  5/159 (3.14%)  2/37 (5.41%)  3/59 (5.08%) 
Oral Herpes  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Otitis Media Acute  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Pharyngitis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Pneumonia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Rhinitis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Sinusitis  1  0/445 (0.00%)  2/154 (1.30%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Upper Respiratory Tract Infection  1  1/445 (0.22%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Urinary Tract Infection  1  2/445 (0.45%)  1/154 (0.65%)  1/159 (0.63%)  1/37 (2.70%)  2/59 (3.39%) 
Vaginal Infection  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Injury, poisoning and procedural complications           
Ankle Fracture  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Contusion  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  0/37 (0.00%)  1/59 (1.69%) 
Epicondylitis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Excoriation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Fall  1  1/445 (0.22%)  3/154 (1.95%)  4/159 (2.52%)  1/37 (2.70%)  0/59 (0.00%) 
Hand Fracture  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Laceration  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Ligament Sprain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Muscle Rupture  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Post Procedural Complication  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Procedural Pain  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Investigations           
Alanine Aminotransferase Increased  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Aspartate Aminotransferase Increased  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Blood Creatinine Decreased  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Blood Pressure Increased  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Blood Triglycerides Increased  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Gamma-Glutamyltransferase Increased  1  0/445 (0.00%)  2/154 (1.30%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Haemoglobin Decreased  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Lasegue's Test Positive  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  1/59 (1.69%) 
Lipase Increased  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Neurological Examination Abnormal  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Nitrite Urine Present  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Prostatic Specifc Antigen Increased  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Protein Urine Present  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Weight Decreased  1  0/445 (0.00%)  3/154 (1.95%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
White Blood Cell Count Increased  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Metabolism and nutrition disorders           
Decreased Appetite  1  12/445 (2.70%)  2/154 (1.30%)  1/159 (0.63%)  3/37 (8.11%)  0/59 (0.00%) 
Diabetes Mellitus  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Dyslipidaemia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  2/37 (5.41%)  0/59 (0.00%) 
Hypercholesterolaemia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Increased Appetite  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/445 (0.22%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  1/59 (1.69%) 
Back Pain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Bursitis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Flank Pain  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Groin Pain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Intervertebral Disc Protusion  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Joint Swelling  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Muscle Fatigue  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Muscle Spasms  1  4/445 (0.90%)  0/154 (0.00%)  1/159 (0.63%)  3/37 (8.11%)  0/59 (0.00%) 
Muscle Twitching  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Musculoskeletal Pain  1  1/445 (0.22%)  2/154 (1.30%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Musculoskeletal Stiffness  1  2/445 (0.45%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Neck Pain  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Osteoarthritis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Pain in Extremity  1  2/445 (0.45%)  4/154 (2.60%)  3/159 (1.89%)  0/37 (0.00%)  1/59 (1.69%) 
Sensation of Heaviness  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Tendonitis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nervous system disorders           
Allodynia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Aphasia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Balance Disorder  1  2/445 (0.45%)  2/154 (1.30%)  2/159 (1.26%)  3/37 (8.11%)  0/59 (0.00%) 
Carotid Arteriosclerosis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Disturbance in Attention  1  2/445 (0.45%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Dizziness  1  51/445 (11.46%)  17/154 (11.04%)  28/159 (17.61%)  11/37 (29.73%)  9/59 (15.25%) 
Dysaesthesia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Dysarthria  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  1/37 (2.70%)  0/59 (0.00%) 
Dysgeusia  1  2/445 (0.45%)  1/154 (0.65%)  3/159 (1.89%)  0/37 (0.00%)  0/59 (0.00%) 
Dyskinesia  1  3/445 (0.67%)  0/154 (0.00%)  0/159 (0.00%)  2/37 (5.41%)  0/59 (0.00%) 
Headache  1  40/445 (8.99%)  10/154 (6.49%)  13/159 (8.18%)  5/37 (13.51%)  7/59 (11.86%) 
Hypoaesthesia  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Hyporeflexia  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Hypotonia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Lethargy  1  3/445 (0.67%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Memory Impairment  1  2/445 (0.45%)  1/154 (0.65%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Mental Impairment  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Movement Disorder  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Muscle Contraction Involuntary  1  0/445 (0.00%)  1/154 (0.65%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Paraesthesia  1  5/445 (1.12%)  1/154 (0.65%)  0/159 (0.00%)  2/37 (5.41%)  0/59 (0.00%) 
Restless Leg Syndrome  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Sciatica  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Sedation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Sensory Loss  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Somnolence  1  29/445 (6.52%)  13/154 (8.44%)  19/159 (11.95%)  11/37 (29.73%)  4/59 (6.78%) 
Speech Disorder  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Syncope  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Tension Headache  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Tremor  1  3/445 (0.67%)  2/154 (1.30%)  2/159 (1.26%)  0/37 (0.00%)  2/59 (3.39%) 
Psychiatric disorders           
Abnormal Dreams  1  3/445 (0.67%)  0/154 (0.00%)  2/159 (1.26%)  1/37 (2.70%)  1/59 (1.69%) 
Aggression  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Agitation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Anxiety  1  4/445 (0.90%)  4/154 (2.60%)  3/159 (1.89%)  3/37 (8.11%)  1/59 (1.69%) 
Apathy  1  2/445 (0.45%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  2/59 (3.39%) 
Confusional State  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Depressed Mood  1  4/445 (0.90%)  3/154 (1.95%)  3/159 (1.89%)  1/37 (2.70%)  0/59 (0.00%) 
Depression  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Disorientation  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Drug Dependence  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Emotional Disorder  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Fear  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Food Aversion  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  2/37 (5.41%)  0/59 (0.00%) 
Hallucination, Visual  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Initial Insomnia  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Insomnia  1  8/445 (1.80%)  3/154 (1.95%)  5/159 (3.14%)  3/37 (8.11%)  3/59 (5.08%) 
Libido decreased  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Listless  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Middle Insomnia  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Mood Swings  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Mood Altered  1  2/445 (0.45%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nervousness  1  1/445 (0.22%)  1/154 (0.65%)  2/159 (1.26%)  1/37 (2.70%)  2/59 (3.39%) 
Nightmare  1  1/445 (0.22%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  3/59 (5.08%) 
Restlessness  1  5/445 (1.12%)  1/154 (0.65%)  1/159 (0.63%)  1/37 (2.70%)  2/59 (3.39%) 
Sleep Disorder Due To General Medical Condition, Insomnia Type  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Sleep Talking  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Sleep disorder  1  4/445 (0.90%)  2/154 (1.30%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Suicidal Ideation  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Tic  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Renal and urinary disorders           
Bladder Discomfort  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Dysuria  1  2/445 (0.45%)  1/154 (0.65%)  3/159 (1.89%)  1/37 (2.70%)  0/59 (0.00%) 
Glycosuria  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Micturition Disorder  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nephrolithiasis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  1/59 (1.69%) 
Oliguria  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Pollakiuria  1  1/445 (0.22%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Renal Colic  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Renal Cyst  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Reproductive system and breast disorders           
Breast Swelling  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Erectile Dysfunction  1  1/445 (0.22%)  0/154 (0.00%)  2/159 (1.26%)  1/37 (2.70%)  0/59 (0.00%) 
Sexual Dysfunctio  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Apnoea  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Cough  1  2/445 (0.45%)  4/154 (2.60%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Dry Throat  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Dysphonia  1  3/445 (0.67%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Dyspnoea  1  5/445 (1.12%)  1/154 (0.65%)  0/159 (0.00%)  2/37 (5.41%)  0/59 (0.00%) 
Hiccups  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Nasal Congestion  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Oropharyngeal Pain  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Respiratory Distress  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Alopecia  1  0/445 (0.00%)  0/154 (0.00%)  2/159 (1.26%)  0/37 (0.00%)  0/59 (0.00%) 
Angioedema  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Dry Skin  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Erythema  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Hyperhidrosis  1  21/445 (4.72%)  18/154 (11.69%)  10/159 (6.29%)  10/37 (27.03%)  5/59 (8.47%) 
Night Sweats  1  0/445 (0.00%)  1/154 (0.65%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Onychoclasis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Pain of Skin  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Petechiae  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Pruritus  1  10/445 (2.25%)  6/154 (3.90%)  1/159 (0.63%)  4/37 (10.81%)  2/59 (3.39%) 
Pruritus Generalised  1  4/445 (0.90%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Rash  1  2/445 (0.45%)  2/154 (1.30%)  1/159 (0.63%)  0/37 (0.00%)  1/59 (1.69%) 
Rash Pruritic  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
Skin Discolouration  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Skin Tightness  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Urticaria  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Surgical and medical procedures           
Tooth Extraction  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Vascular disorders           
Blood Pressure Fluctuation  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  1/37 (2.70%)  0/59 (0.00%) 
Flushing  1  2/445 (0.45%)  1/154 (0.65%)  0/159 (0.00%)  1/37 (2.70%)  0/59 (0.00%) 
Haematoma  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Hot Flush  1  10/445 (2.25%)  0/154 (0.00%)  0/159 (0.00%)  3/37 (8.11%)  1/59 (1.69%) 
Hypertension  1  3/445 (0.67%)  1/154 (0.65%)  5/159 (3.14%)  0/37 (0.00%)  1/59 (1.69%) 
Hypertensive crisis  1  1/445 (0.22%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Hypotension  1  2/445 (0.45%)  0/154 (0.00%)  2/159 (1.26%)  1/37 (2.70%)  1/59 (1.69%) 
Thrombophlebitis  1  0/445 (0.00%)  1/154 (0.65%)  0/159 (0.00%)  0/37 (0.00%)  0/59 (0.00%) 
Thrombosis  1  0/445 (0.00%)  0/154 (0.00%)  1/159 (0.63%)  0/37 (0.00%)  0/59 (0.00%) 
Venous Thrombosis Limb  1  0/445 (0.00%)  0/154 (0.00%)  0/159 (0.00%)  0/37 (0.00%)  1/59 (1.69%) 
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
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Trials
Organization: Grünenthal GmbH
Phone: +49 241 569 3223
Layout table for additonal information
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT01352741    
Other Study ID Numbers: 247251
2010-019998-14 ( EudraCT Number )
KF5503/58 ( Other Identifier: Grünenthal GmbH )
First Submitted: April 12, 2011
First Posted: May 12, 2011
Results First Submitted: May 10, 2016
Results First Posted: August 12, 2016
Last Update Posted: October 28, 2019