Trial Outcomes & Findings for Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking WHO Step III Analgesics But Showing a Lack of Tolerability (NCT NCT00986258)

NCT ID: NCT00986258

Last Updated: 2019-01-09

Results Overview

Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

136 participants

Primary outcome timeframe

6 weeks

Results posted on

2019-01-09

Participant Flow

The enrollment of the first participant was on the 30 October 2009 and was prematurely terminated, due to slow recruitment, on 21 January 2011 (when the last subject completed the last follow-up examination).

The Trial had a duration of 13 weeks. The one week Observation Period did not involve dosing with Tapentadol. For Tapentadol analyses purposes the first 6 weeks of dosing with Tapentadol are reported as one period, Titration and Optimal Dose Period. The last 6 weeks on Tapentadol are reported as the Maintenance Period.

Participant milestones

Participant milestones
Measure
Tapentadol Prolonged Release
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks.Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Observation Period
STARTED
136
Observation Period
COMPLETED
125
Observation Period
NOT COMPLETED
11
Titration and Optimal Dose Period
STARTED
125
Titration and Optimal Dose Period
COMPLETED
102
Titration and Optimal Dose Period
NOT COMPLETED
23
Maintenance Period
STARTED
102
Maintenance Period
COMPLETED
93
Maintenance Period
NOT COMPLETED
9

Reasons for withdrawal

Reasons for withdrawal
Measure
Tapentadol Prolonged Release
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks.Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Observation Period
Not eligible to be dosed
11
Titration and Optimal Dose Period
Adverse Event
15
Titration and Optimal Dose Period
Lack of Efficacy
3
Titration and Optimal Dose Period
Withdrawal by Subject
3
Titration and Optimal Dose Period
Non-Compliance
1
Titration and Optimal Dose Period
Other
1
Maintenance Period
Adverse Event
5
Maintenance Period
Lack of Efficacy
2
Maintenance Period
Withdrawal by Subject
2

Baseline Characteristics

Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking WHO Step III Analgesics But Showing a Lack of Tolerability

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Tapentadol Prolonged Release
n=125 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Age, Continuous
57.1 years
STANDARD_DEVIATION 12.00 • n=5 Participants
Sex: Female, Male
Female
76 Participants
n=5 Participants
Sex: Female, Male
Male
49 Participants
n=5 Participants
Region of Enrollment
France
1 participants
n=5 Participants
Region of Enrollment
Czechia
24 participants
n=5 Participants
Region of Enrollment
Spain
21 participants
n=5 Participants
Region of Enrollment
Poland
9 participants
n=5 Participants
Region of Enrollment
Belgium
17 participants
n=5 Participants
Region of Enrollment
Netherlands
14 participants
n=5 Participants
Region of Enrollment
Germany
34 participants
n=5 Participants
Region of Enrollment
Switzerland
5 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Per Protocol Set. Last Observation Carried Forward (LOCF).

Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=94 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Number of Participants That Responded to Treatment
76 participants

SECONDARY outcome

Timeframe: Baseline

Population: Intention to Treat

For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=122 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Average Pain Intensity Before the Start of Tapentadol Treatment
4.8 units on a scale
Standard Deviation 0.75

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 weeks)

Population: Intention to treat (ITT)

For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A negative value indicates a reduction in pain intensity from the baseline average pain intensity.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=101 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.
-0.9 units on a scale
Standard Deviation 1.89

SECONDARY outcome

Timeframe: Baseline; End of Week 12 (12 weeks)

Population: Intention to treat (ITT).

For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A Negative value indicates a reduction in pain intensity from the baseline average pain intensity.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=93 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.
-1.3 units on a scale
Standard Deviation 2.10

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intention to treat (ITT)

In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=101 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Patient Global Impression of Change
Very much improved
5 participants
Patient Global Impression of Change
Much improved
29 participants
Patient Global Impression of Change
Minimally improved
47 participants
Patient Global Impression of Change
No change
11 participants
Patient Global Impression of Change
Minimally worse
6 participants
Patient Global Impression of Change
Much worse
3 participants
Patient Global Impression of Change
Very much worse
0 participants

SECONDARY outcome

Timeframe: Baseline; End of Week 12 (12 Weeks)

Population: Intention to treat (ITT)

In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=93 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Patient Global Impression of Change
Very much improved
9 participants
Patient Global Impression of Change
Much improved
34 participants
Patient Global Impression of Change
Minimally improved
38 participants
Patient Global Impression of Change
No change
9 participants
Patient Global Impression of Change
Minimally worse
2 participants
Patient Global Impression of Change
Much worse
1 participants
Patient Global Impression of Change
Very much worse
0 participants

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intention to treat (ITT). For the sub-scores "Role Emotional" and "Role Physical" there were 98 participants, for sub-scores "Physical Functioning", "Vitality" and "Mental Health" there were 99 participants, for sub-score "General Health" there were 100 participants with data available for the change of these sub-scores from baseline to visit 6.

The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (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. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=101 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Change in the Health Survey Scores Form (SF-36)
Physical Functioning
8.4 units on a scale
Standard Deviation 18.65
Change in the Health Survey Scores Form (SF-36)
Bodily Pain
11.6 units on a scale
Standard Deviation 20.00
Change in the Health Survey Scores Form (SF-36)
General Health
5.9 units on a scale
Standard Deviation 15.10
Change in the Health Survey Scores Form (SF-36)
Vitality
9.2 units on a scale
Standard Deviation 17.44
Change in the Health Survey Scores Form (SF-36)
Social Functioning
8.0 units on a scale
Standard Deviation 24.47
Change in the Health Survey Scores Form (SF-36)
Role Emotional
-1.4 units on a scale
Standard Deviation 42.26
Change in the Health Survey Scores Form (SF-36)
Mental Health
5.1 units on a scale
Standard Deviation 16.73
Change in the Health Survey Scores Form (SF-36)
Role Physical
6.9 units on a scale
Standard Deviation 28.89

SECONDARY outcome

Timeframe: Baseline; End of Week 12 (12 Weeks)

Population: Intention to Treat (ITT). For the sub-scores "Role Emotional" and "Role Physical", there were only 91 participants with data available for the change of these sub-scores from baseline to visit 12.

The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (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. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=93 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Change in the Health Survey Scores Form (SF-36)
Physical Functioning
10.5 units on a scale
Standard Deviation 19.96
Change in the Health Survey Scores Form (SF-36)
Bodily Pain
14.1 units on a scale
Standard Deviation 22.84
Change in the Health Survey Scores Form (SF-36)
General Health
5.7 units on a scale
Standard Deviation 14.98
Change in the Health Survey Scores Form (SF-36)
Vitality
12.0 units on a scale
Standard Deviation 21.03
Change in the Health Survey Scores Form (SF-36)
Social Functioning
11.7 units on a scale
Standard Deviation 27.07
Change in the Health Survey Scores Form (SF-36)
Role Emotional
13.9 units on a scale
Standard Deviation 43.06
Change in the Health Survey Scores Form (SF-36)
Mental Health
9.8 units on a scale
Standard Deviation 17.70
Change in the Health Survey Scores Form (SF-36)
Role Physical
10.7 units on a scale
Standard Deviation 31.65

SECONDARY outcome

Timeframe: Baseline

Population: Intention to treat (ITT). For the sub-scores "Overall Score" and "Pressing Pain" there were only 69 participants with data available at baseline.

All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean for each neuropathic symptom in the sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=71 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score burning pain
0.41 units on a scale
Standard Deviation 0.284
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score pressing pain
0.405 units on a scale
Standard Deviation 0.23
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paroxysmal pain
0.422 units on a scale
Standard Deviation 0.221
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score evoked pain
0.385 units on a scale
Standard Deviation 0.216
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paresthesia / dysthesia
0.424 units on a scale
Standard Deviation 0.233
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Overall score
0.408 units on a scale
Standard Deviation 0.158

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT). For the sub-scores "Overall Score" and "Pressing Pain" there were only 60 participants with data available at Visit 6.

All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=61 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score burning pain
0.32 units on a scale
Standard Deviation 0.273
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score pressing pain
0.322 units on a scale
Standard Deviation 0.229
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paroxysmal pain
0.271 units on a scale
Standard Deviation 0.231
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score evoked pain
0.274 units on a scale
Standard Deviation 0.216
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paresthesia / dysthesia
0.302 units on a scale
Standard Deviation 0.21
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Overall score
0.297 units on a scale
Standard Deviation 0.178

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT).

All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean (average) for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=56 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score burning pain
0.27 units on a scale
Standard Deviation 0.281
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score pressing pain
0.302 units on a scale
Standard Deviation 0.235
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paroxysmal pain
0.254 units on a scale
Standard Deviation 0.255
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score evoked pain
0.273 units on a scale
Standard Deviation 0.252
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Sub-score paresthesia / dysthesia
0.299 units on a scale
Standard Deviation 0.239
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
Overall score
0.280 units on a scale
Standard Deviation 0.211

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intention to treat (ITT). 35 participants with previous oxycodone treatment.

Tapentadol was compared to Oxycodone with Oxycodone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Oxycodone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Oxycodone.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=35 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Mean Equipotency Ratio of Tapentadol Compared to Oxycodone
5.3 Ratio

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intention to treat (ITT). 24 participants with previous buprenorphine treatment.

Tapentadol was compared to Buprenorphine with Buprenorphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Buprenorphine.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=24 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine
210.0 Ratio

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intent to treat (ITT). 22 participants with previous transdermal fentanyl treatment.

Tapentadol was compared to Transdermal Fentanyl with Fentanyl set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Transdermal Fentanyl was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Fentanyl.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=22 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Mean Equipotency Ratio of Tapentadol Compared to Fentanyl
250.7 Ratio

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intent to treat (ITT). 14 participants with previous morphine treatment.

Tapentadol was compared to Morphine with Morphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Morphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Morphine.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=14 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Mean Equipotency Ratio of Tapentadol Compared to Morphine
3.0 Ratio

SECONDARY outcome

Timeframe: Baseline; End of Week 6 (6 Weeks)

Population: Intention to treat (ITT). 8 participants with previous hydromorphone treatment.

Tapentadol was compared to Hydromorphone with Hydromorphone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Hydromorphone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Hydromorphone.

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=8 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
Subgroup of participants with a score between 19 and 38.
Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone
10.5 Ratio

SECONDARY outcome

Timeframe: Baseline

Population: Intention to treat (ITT).

The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=44 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
n=24 Participants
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
n=50 Participants
Subgroup of participants with a score between 19 and 38.
painDETECT Assessment at Baseline
6.5 units on a scale
Standard Deviation 3.90
14.7 units on a scale
Standard Deviation 2.39
21.1 units on a scale
Standard Deviation 3.39

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT).

The baseline painDETECT score was reassessed at the end of Week 6. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=35 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
n=20 Participants
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
n=45 Participants
Subgroup of participants with a score between 19 and 38.
painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment
7.5 units on a scale
Standard Deviation 4.18
10.5 units on a scale
Standard Deviation 4.75
17.4 units on a scale
Standard Deviation 5.95

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT).

The baseline painDETECT score was reassessed at the end of Week 12. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

Outcome measures

Outcome measures
Measure
Tapentadol Prolonged Release
n=33 Participants
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached.
Baseline painDETECT Unclear Group
n=19 Participants
Subgroup of participants with a score between 13 and 18.
Baseline painDETECT Positive Group
n=40 Participants
Subgroup of participants with a score between 19 and 38.
painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment
6.8 units on a scale
Standard Deviation 4.85
8.6 units on a scale
Standard Deviation 5.43
16.5 units on a scale
Standard Deviation 7.17

Adverse Events

Tapentadol Prolonged Release

Serious events: 11 serious events
Other events: 85 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Tapentadol Prolonged Release
n=125 participants at risk
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release once 500 mg tapentadol prolonged release dose was reached.
Cardiac disorders
Cardiac failure
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Cardiac disorders
Myocardial infarction
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Cardiac disorders
Trachycardia
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Gastrointestinal disorders
Abdominal pain
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
General disorders
Chest pain
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
General disorders
Drug withdrawal syndrome
1.6%
2/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
General disorders
Oedema
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Infections and infestations
pneumonia
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Nervous system disorders
Headache
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Nervous system disorders
Subarachnoid haemorrhage
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Renal and urinary disorders
Calculus urinary
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Renal and urinary disorders
Nephrolithiasis
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Vascular disorders
Haematoma
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Vascular disorders
Hypertension
0.80%
1/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.

Other adverse events

Other adverse events
Measure
Tapentadol Prolonged Release
n=125 participants at risk
All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release once 500 mg tapentadol prolonged release dose was reached.
Gastrointestinal disorders
Abdominal pain upper
5.6%
7/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Gastrointestinal disorders
Constipation
12.0%
15/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Gastrointestinal disorders
Diarrhoea
10.4%
13/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Gastrointestinal disorders
Dry mouth
6.4%
8/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Gastrointestinal disorders
Nausea
15.2%
19/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
General disorders
Drug Withdrawal Syndrome
20.8%
26/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
General disorders
Fatigue
10.4%
13/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Nervous system disorders
Dizziness
12.8%
16/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Nervous system disorders
Headache
14.4%
18/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Psychiatric disorders
Insomnia
12.8%
16/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.
Skin and subcutaneous tissue disorders
Hyperhidrosis
8.0%
10/125 • In total, subjects were to be treated for up to 12 weeks with tapentadol.

Additional Information

Director of Clinical Trials

Grünenthal GmbH

Phone: +49 241 569 3223

Results disclosure agreements

  • Principal investigator is a sponsor employee Grünenthal reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
  • Publication restrictions are in place

Restriction type: OTHER