Trial Outcomes & Findings for Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics (NCT NCT00983385)

NCT ID: NCT00983385

Last Updated: 2019-01-15

Results Overview

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 participant assessment on the 0 to 10 scale. A negative value indicates a reduction in pain intensity.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 208 participants
• Primary outcome timeframe: Baseline; End of Week 6 (6 Weeks)
• Results posted on: 2019-01-15

Participant Flow

The trial started on 30 September 2009 with enrollment of the first subject and the last follow-up examination took place on 06 July 2010.

During the observation period (3 to 7 days in length) subjects recorded their analgesic medication intake and pain intensity. Prior to intake of tapentadol.

Participant milestones

Measure	Tapentadol All participants started with 50 mg tapentadol hydrochloride prolonged release (PR) (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride immediate release (IR) 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.
Observation Period STARTED	208
Observation Period COMPLETED	176
Observation Period NOT COMPLETED	32
Titration and Optimal Dose Period STARTED	176
Titration and Optimal Dose Period COMPLETED	140
Titration and Optimal Dose Period NOT COMPLETED	36
Maintenance Period STARTED	140
Maintenance Period COMPLETED	117
Maintenance Period NOT COMPLETED	23

Reasons for withdrawal

Measure	Tapentadol All participants started with 50 mg tapentadol hydrochloride prolonged release (PR) (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride immediate release (IR) 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.
Observation Period Not eligible to be dosed	20
Observation Period Not Evaluable due to Non Compliance	12

Baseline Characteristics

Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics

Baseline characteristics by cohort

Measure	Tapentadol n=176 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.
Age, Continuous	59.7 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants
Region of Enrollment France	14 participants n=5 Participants
Region of Enrollment Spain	52 participants n=5 Participants
Region of Enrollment Poland	11 participants n=5 Participants
Region of Enrollment Austria	26 participants n=5 Participants
Region of Enrollment Germany	46 participants n=5 Participants
Region of Enrollment United Kingdom	12 participants n=5 Participants
Region of Enrollment Switzerland	3 participants n=5 Participants
Region of Enrollment Italy	12 participants n=5 Participants
Prior analgesic medication Participants pretreated with opioids	88 participants n=5 Participants
Prior analgesic medication Participants opioid naive (Step 1 analgesics)	87 participants n=5 Participants
Prior analgesic medication Unknown	1 participants n=5 Participants

PRIMARY outcome

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

Population: Intention to treat. Last Observation Carried Forward (LOCF)

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 participant assessment on the 0 to 10 scale. A negative value indicates a reduction in pain intensity.

Outcome measures

Measure	Tapentadol n=174 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
The Primary Endpoint is Defined as the Change of the Average Pain Intensity Score on an 11-point NRS-3 at Week 6 From Week -1 (Baseline).	-2.8 Units on a scale Standard Deviation 2.12	—	—

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

Measure	Tapentadol n=134 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 at End of Titration and Optimal Dose Period Very much improved	12 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period Much improved	55 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period Minimally improved	49 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period No change	10 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period Minimally worse	5 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period Much worse	2 participants	—	—
Patient Global Impression of Change at End of Titration and Optimal Dose Period Very much worse	1 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

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 at End of the Maintenance Period Much worse	0 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period Very much improved	19 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period Much improved	42 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period Minimally improved	23 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period No change	5 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period Minimally worse	0 participants	—	—
Patient Global Impression of Change at End of the Maintenance Period Very much worse	0 participants	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT)

The Scores Form 36 (SF-36) includes several brief board 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

Measure	Tapentadol n=133 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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) at End of Titration and Optimal Dose Period Physical Functioning	14.1 Units on a scale Standard Deviation 17.23	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Bodily Pain	21.7 Units on a scale Standard Deviation 21.39	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period General Health	6.3 Units on a scale Standard Deviation 16.18	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Vitality	8.0 Units on a scale Standard Deviation 20.28	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Social Functioning	10.7 Units on a scale Standard Deviation 25.84	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Role Emotional	14.8 Units on a scale Standard Deviation 43.98	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Mental Health	7.5 Units on a scale Standard Deviation 18.22	—	—
Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period Role Physical	25.0 Units on a scale Standard Deviation 40.47	—	—

SECONDARY outcome

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

The Scores Form 36 (SF-36) includes several brief board 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

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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) at End of Maintenance Period Physical Functioning	15.7 Units on a scale Standard Deviation 21.95	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Bodily Pain	24.4 Units on a scale Standard Deviation 21.96	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period General Health	10.3 Units on a scale Standard Deviation 14.95	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Vitality	9.5 Units on a scale Standard Deviation 18.43	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Social Functioning	13.2 Units on a scale Standard Deviation 27.85	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Role Emotional	18.6 Units on a scale Standard Deviation 44.17	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Mental Health	12.0 Units on a scale Standard Deviation 18.33	—	—
Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period Role Physical	29.2 Units on a scale Standard Deviation 48.30	—	—

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

Measure	Tapentadol n=49 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	Baseline painDETECT Unclear Group n=41 Participants Subgroup of participants with a score between 13 and 18.	Baseline painDETECT Positive Group n=81 Participants Subgroup of participants with a score between 19 and 38.
painDETECT Assessment at Baseline	7.1 units on a scale Standard Deviation 3.26	13.2 units on a scale Standard Deviation 3.36	21.4 units on a scale Standard Deviation 5.05

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

Measure	Tapentadol n=34 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	Baseline painDETECT Unclear Group n=32 Participants Subgroup of participants with a score between 13 and 18.	Baseline painDETECT Positive Group n=64 Participants Subgroup of participants with a score between 19 and 38.
painDETECT Assessment for Participants at End of Titration and Optimal Dose Period	5.5 units on a scale Standard Deviation 3.60	9.8 units on a scale Standard Deviation 6.21	14.4 units on a scale Standard Deviation 7.05

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

Measure	Tapentadol n=23 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	Baseline painDETECT Unclear Group n=21 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 at End of the Maintenance Period	5.7 units on a scale Standard Deviation 4.22	7.1 units on a scale Standard Deviation 6.13	11.2 units on a scale Standard Deviation 7.52

SECONDARY outcome

Timeframe: Baseline Visit

Population: Intention to treat (ITT).

Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales.

Outcome measures

Measure	Tapentadol n=124 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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) Subscores and Overall Score Assessment at Baseline Sub-score burning pain	0.470 units on a scale Standard Deviation 0.310	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline Sub-score pressing pain	0.549 units on a scale Standard Deviation 0.243	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline Sub-score paroxysmal pain	0.575 units on a scale Standard Deviation 0.243	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline Sub-score evoked pain	0.391 units on a scale Standard Deviation 0.263	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline Sub-score paresthesia / dysthesia	0.539 units on a scale Standard Deviation 0.273	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline Overall score	0.497 units on a scale Standard Deviation 0.180	—	—

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT).

Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales.

Outcome measures

Measure	Tapentadol n=97 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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) Subscores and Overall Score at End of Titration and Optimal Dose Period Sub-score burning pain	0.260 units on a scale Standard Deviation 0.281	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period Sub-score pressing pain	0.316 units on a scale Standard Deviation 0.257	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period Sub-score paroxysmal pain	0.293 units on a scale Standard Deviation 0.258	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period Sub-score evoked pain	0.230 units on a scale Standard Deviation 0.221	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period Sub-score paresthesia / dysthesia	0.303 units on a scale Standard Deviation 0.2722	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period Overall score	0.278 units on a scale Standard Deviation 0.204	—	—

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT).

Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales.

Outcome measures

Measure	Tapentadol n=66 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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) Subscores and Overall Score Assessment at End of the Maintenance Period Sub-score burning pain	0.180 units on a scale Standard Deviation 0.237	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period Sub-score pressing pain	0.235 units on a scale Standard Deviation 0.218	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period Sub-score paroxysmal pain	0.211 units on a scale Standard Deviation 0.225	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period Sub-score evoked pain	0.175 units on a scale Standard Deviation 0.188	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period Sub-score paresthesia / dysthesia	0.231 units on a scale Standard Deviation 0.270	—	—
Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period Overall score	0.206 units on a scale Standard Deviation 0.198	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT), Last Observation Carried Forward (LOCF).

Change in mean score NPSI, questionnaire evaluates symptoms of neuropathic pain. Ten pain descriptors questions are answered on an 11-point scale 0 (no pain)-10 (most intense pain imaginable). The NPSI derives a total intensity score calculated from the subscores. A negative value indicates improvement in neuropathic symptoms.

Outcome measures

Measure	Tapentadol n=95 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of Titration and Optimal Dose Period	-0.224 Units on a scale Standard Deviation 0.213	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT), Last Observation Carried Forward (LOCF).

Change in mean score NPSI, questionnaire evaluates symptoms of neuropathic pain. Ten pain descriptors questions are answered on an 11-point scale 0 (no pain)-10 (most intense pain imaginable). The NPSI derives a total intensity score calculated from the subscores. A negative value indicates improvement in neuropathic symptoms.

Outcome measures

Measure	Tapentadol n=65 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of the Maintenance Period	-0.296 units on a scale Standard Deviation 0.228	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT). painDETECT negative subpopulation - 35 participants. Unclear and positive painDETECT subpopulation - 98 participants.

The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is 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 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.

Outcome measures

Measure	Tapentadol n=133 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period. All participants	0.244 Units on a scale Standard Deviation 0.315	—	—
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period. Participants painDETECT negative	0.229 Units on a scale Standard Deviation 0.321	—	—
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period. Participant painDETECT unclear or positive	0.249 Units on a scale Standard Deviation 0.315	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT). painDETECT negative subpopulation - 34 participants. Unclear and positive painDETECT subpopulation - 97 participants.

EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement.

Outcome measures

Measure	Tapentadol n=131 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period. All participants	12.2 Units on a scale Standard Deviation 25.08	—	—
Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period. Participants painDETECT negative	7.6 Units on a scale Standard Deviation 19.74	—	—
Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period. Participant painDETECT unclear or positive	13.8 Units on a scale Standard Deviation 26.61	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT). Unclear and positive painDETECT subpopulation - 66 participants. painDETECT negative subpopulation - 23 participants.

The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is 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 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period All participants	0.282 units on a scale Standard Deviation 0.297	—	—
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period Participants painDETECT negative	0.182 units on a scale Standard Deviation 0.252	—	—
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period Participants painDETECT unclear or positive	0.316 units on a scale Standard Deviation 0.306	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT). painDETECT negative subpopulation - 23 participants. Unclear and positive painDETECT subpopulation - 66 participants.

EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement.

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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 Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period Participants painDETECT negative	14.7 Units on a scale Standard Deviation 26.68	—	—
Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period All participants	20.0 Units on a scale Standard Deviation 27.27	—	—
Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period Participant painDETECT unclear or positive	21.8 Units on a scale Standard Deviation 27.44	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT).

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

Outcome measures

Measure	Tapentadol n=134 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Very much worse	1 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Very much improved	17 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Much improved	53 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Minimally improved	49 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period No change	11 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Minimally worse	2 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period Much worse	1 participants	—	—

SECONDARY outcome

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

Population: Intention to treat (ITT).

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

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Clinical Global Impression of Change (All Participants) at End of Maintenance Period Very much improved	17 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Maintenance Period Much improved	45 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Maintenance Period Minimally improved	22 participants	—	—
Clinical Global Impression of Change (All Participants) at End of Maintenance Period No change	5 participants	—	—

SECONDARY outcome

Timeframe: Baseline

Population: Negative painDETECT subpopulation - 49 participants Unclear and positive painDETECT subpopulation - 124 participants Intention to Treat (ITT).

Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=173 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline All participants	7.8 units on a scale Standard Deviation 4.32	—	—
Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline Negative painDETECT participants	6.2 units on a scale Standard Deviation 4.10	—	—
Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline Unclear and positive painDETECT participants	8.4 units on a scale Standard Deviation 4.26	—	—

SECONDARY outcome

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

Population: Negative painDETECT subpopulation - 34 participants Unclear and positive painDETECT subpopulation - 94 participants Intention to Treat (ITT).

Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=128 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period All participants	-1.2 units on a scale Standard Deviation 3.36	—	—
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period Negative painDETECT participants	-0.3 units on a scale Standard Deviation 2.93	—	—
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period Unclear and positive painDETECT participants	-1.5 units on a scale Standard Deviation 3.47	—	—

SECONDARY outcome

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

Population: Negative painDETECT subpopulation - 23 participants Unclear and positive painDETECT subpopulation - 66 participants Intention to Treat (ITT).

Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period All participants	-2.1 units on a scale Standard Deviation 3.67	—	—
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period Negative painDETECT participants	-0.8 units on a scale Standard Deviation 2.82	—	—
Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period Unclear and positive painDETECT participants	-2.5 units on a scale Standard Deviation 3.85	—	—

SECONDARY outcome

Timeframe: Baseline

Population: Negative painDETECT subpopulation - 49 participants Unclear and positive painDETECT subpopulation - 124 participants Intention to Treat (ITT).

Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=173 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale: Depression Score at Baseline All participants	7.9 units on a scale Standard Deviation 4.27	—	—
Hospital Anxiety Depression Scale: Depression Score at Baseline Negative painDETECT participants	6.5 units on a scale Standard Deviation 3.96	—	—
Hospital Anxiety Depression Scale: Depression Score at Baseline Unclear and positive painDETECT participants	8.5 units on a scale Standard Deviation 4.27	—	—

SECONDARY outcome

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

Population: Negative painDETECT subpopulation - 34 participants Unclear or positive painDETECT subpopulation - 94 participants Intention to Treat (ITT).

Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=128 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period. All participants	-1.2 units on a scale Standard Deviation 3.40	—	—
Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period. Negative painDETECT participants	-1.0 units on a scale Standard Deviation 3.15	—	—
Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period. Unclear and positive painDETECT participants	-1.3 units on a scale Standard Deviation 3.50	—	—

SECONDARY outcome

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

Population: Negative painDETECT subpopulation - 23 participants Unclear and positive painDETECT subpopulation - 66 participants. Intention to Treat (ITT).

Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst.

HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period All participants	-1.6 units on a scale Standard Deviation 3.24	—	—
Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period Negative painDETECT participants	-0.5 units on a scale Standard Deviation 2.86	—	—
Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period Unclear and positive painDETECT participants	-2.0 units on a scale Standard Deviation 3.30	—	—

SECONDARY outcome

Timeframe: Week 6

Population: Negative painDETECT subpopulation - 22 participants Unclear painDETECT subpopulation - 15 participants Positive painDETECT subpopulation - 22 participants Intention to treat (ITT).

Tapentadol hydrochloride PR dose after 5 weeks of titration which was to be kept stable during the remained of the trial.

Outcome measures

Measure	Tapentadol n=59 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period. Negative painDETECT participants	336.4 milligrams (mg) Standard Deviation 132.90	—	—
Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period. Unclear painDETECT participants	293.3 milligrams (mg) Standard Deviation 103.28	—	—
Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period. Positive painDETECT participants	268.2 milligrams (mg) Standard Deviation 132.33	—	—

SECONDARY outcome

Timeframe: Baseline

Participants were requested to rate their previous analgesic medication on a 5-point scale. Previous analgesic medication was rated as excellent, very good, good, fair and poor.

Outcome measures

Measure	Tapentadol n=175 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Participant's Satisfaction With Previous Analgesic Treatment at Baseline Good	2 participants	—	—
Participant's Satisfaction With Previous Analgesic Treatment at Baseline Fair	98 participants	—	—
Participant's Satisfaction With Previous Analgesic Treatment at Baseline Poor	75 participants	—	—

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT).

Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor.

Outcome measures

Measure	Tapentadol n=134 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. Excellent	12 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. Very Good	29 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. Good	64 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. Fair	22 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. Poor	7 participants	—	—

SECONDARY outcome

Timeframe: End of Week 8

Population: Intention to treat (ITT).

Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor.

Outcome measures

Measure	Tapentadol n=122 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. Excellent	14 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. Very Good	30 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. Good	58 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. Fair	17 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. Poor	3 participants	—	—

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT).

Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor.

Outcome measures

Measure	Tapentadol n=89 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. Excellent	10 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. Very Good	38 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. Good	28 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. Fair	11 participants	—	—
Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. Poor	2 participants	—	—

SECONDARY outcome

Timeframe: Baseline

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 31 participants. Unclear and positive painDETECT subpopulation - 56 participants

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

Measure	Tapentadol n=87 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline. Negative painDETECT participants	7.3 Units on a scale Standard Deviation 0.78	—	—
Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline. Unclear and positive painDETECT participants	7.4 Units on a scale Standard Deviation 1.00	—	—

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 22 participants. Unclear and positive painDETECT subpopulation - 37 participants

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

Measure	Tapentadol n=59 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. Negative painDETECT participants	4.0 Units on a scale Standard Deviation 1.77	—	—
NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. Unclear and positive painDETECT participants	4.1 Units on a scale Standard Deviation 1.86	—	—

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 15 participants. Unclear and positive painDETECT subpopulation - 24 participants

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

Measure	Tapentadol n=39 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period. Negative painDETECT participants	3.1 Units on a scale Standard Deviation 1.81	—	—
NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period. Unclear and positive painDETECT participants	3.4 Units on a scale Standard Deviation 2.32	—	—

SECONDARY outcome

Timeframe: Baseline

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 18 participants. Unclear and positive painDETECT subpopulation - 70 participants

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

Measure	Tapentadol n=88 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline. Negative painDETECT participants	6.7 Units on a scale Standard Deviation 0.96	—	—
Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline. Unclear and positive painDETECT participants	7.6 Units on a scale Standard Deviation 1.07	—	—

SECONDARY outcome

Timeframe: End of Week 6

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 13 participants. Unclear and positive painDETECT subpopulation - 62 participants

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

Measure	Tapentadol n=75 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. Negative painDETECT participants	4.2 Units on a scale Standard Deviation 1.96	—	—
NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. Unclear and positive painDETECT participants	4.4 Units on a scale Standard Deviation 2.26	—	—

SECONDARY outcome

Timeframe: End of Week 12

Population: Intention to treat (ITT). Negative painDETECT subpopulation - 8 participants. Unclear and positive painDETECT subpopulation - 42 participants

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

Measure	Tapentadol n=50 Participants All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached. Tapentadol PR was administered for 12 weeks in total.	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.
NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period. Negative painDETECT participants	3.4 Units on a scale Standard Deviation 1.92	—	—
NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period. Unclear and positive painDETECT participants	3.2 Units on a scale Standard Deviation 1.94	—	—

Adverse Events

Tapentadol

Serious events: 7 serious events

Other events: 148 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tapentadol n=176 participants at risk All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached.
Renal and urinary disorders Renal colic	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Infections and infestations Sepsis	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Psychiatric disorders Confusional state	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Investigations Blood insulin abnormal	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Hepatobiliary disorders Cholecystitis acute	0.57% 1/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.

Other adverse events

Measure	Tapentadol n=176 participants at risk All participants started with 50 mg tapentadol hydrochloride PR (twice daily). The dose of tapentadol hydrochloride PR was adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol hydrochloride was kept stable. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol hydrochloride IR 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 hydrochloride IR once 500 mg tapentadol hydrochloride PR dose was reached.
Gastrointestinal disorders Abdominal upper pain	5.1% 9/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Gastrointestinal disorders Constipation	11.4% 20/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Gastrointestinal disorders Diarrhoea	11.4% 20/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Gastrointestinal disorders Dry mouth	15.3% 27/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Gastrointestinal disorders Nausea	21.0% 37/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Gastrointestinal disorders Vomiting	6.2% 11/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
General disorders Fatigue	12.5% 22/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Infections and infestations Nasopharyngitis	11.4% 20/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Nervous system disorders Dizziness	17.6% 31/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Nervous system disorders Headache	16.5% 29/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Nervous system disorders Somnolence	10.2% 18/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.1% 9/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Skin and subcutaneous tissue disorders Pruritus	5.1% 9/176 • 12 weeks The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.

Additional Information

Director of Clinical Trials

Grünenthal GmbH

Phone: +49 241 569

Email: Clinical-Trials@grunenthal.com

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