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

• Sponsor: Grünenthal GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00983385
• Collaborator: (none)
• Enrollment: 208
• Locations: 46
• Arm: 1
• Actual Duration (Months): 9.2
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The main objective of the study is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride prolonged release in subjects suffering from severe chronic low back pain (LBP) who are taking either WHO Step I or Step II analgesics or no regular analgesics. This is a clinical effectiveness trial designed to establish a link between anticipated clinical outcomes and the clinical practice by means of selected measures of clinical and subject-reported outcome.

The trial will compare the effectiveness of previous analgesic treatment (either WHO Step I or Step II analgesics or no regular analgesics) with that of tapentadol hydrochloride prolonged release (PR) treatment during defined periods of evaluation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain; Low Back Pain	Drug: Tapentadol PR; Other: Observation period; Drug: Tapentadol PR	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 208 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Evaluation of the Effectiveness and Tolerability of Tapentadol Hydrochloride Prolonged Release, and Tapentadol Hydrochloride Immediate Release on Demand, in Subjects With Uncontrolled Severe Chronic Nociceptive, Mixed or Neuropathic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics.
• Actual Study Start Date: Sep 30, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Jul 6, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tapentadol Tapentadol PR was given orally twice a day. A maximum of 2 oral Tapentadol immediate release (IR) tablets per day, with a minimum of a 4 hour interval between doses, were taken if there were acute pain episodes. The total daily dose of Tapentadol PR and IR were not permitted to exceed 500 mg per day.

Drug: Tapentadol PR; Tapentadol Prolonged Release (PR) Titration and Optimal Dose Period: Starting at 50 mg Tapentadol PR twice daily, adjusted with 50 mg PR steps (upwards or downwards) as necessary to achieve a balance between pain relief and a satisfactory level of tolerability. Participants were not permitted to exceed a dose of 500 mg of Tapentadol per day.; Other Names: Palexia® Nucynta® ; Other: Observation period; Eligibility assessment period to characterize the baseline over a one week period (week -1). Participants continued their previous treatment prior to allocation to tapentadol, if eligible.; Drug: Tapentadol PR; Maintenance Period: In this period participants continued Tapentadol Prolonged Release (PR) on the dose established in the Titration and Optimal Dose Period. Tapentadol IR participants were not permitted to exceed a total daily tapentadol dose of 500 mg.; Other Names: Palexia® Nucynta®

Outcome Measures

Primary Outcome Measures

1. 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). [Baseline; End of Week 6 (6 Weeks)]

   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.

Secondary Outcome Measures

1. Patient Global Impression of Change at End of Titration and Optimal Dose Period [Baseline; End of Week 6 (6 Weeks)]

   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.

2. Patient Global Impression of Change at End of the Maintenance Period [Baseline; End of Week 12 (12 weeks)]

   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.

3. Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period [Baseline; End of Week 6 (6 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.

4. Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period [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.

5. painDETECT Assessment at Baseline [Baseline]

   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".

6. painDETECT Assessment for Participants at End of Titration and Optimal Dose Period [End of Week 6]

   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".

7. painDETECT Assessment for Participants at End of the Maintenance Period [End of Week 12]

   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".

8. Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline [Baseline Visit]

   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.

9. Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period [End of Week 6]

   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.

10. Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period [End of Week 12]

    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.

11. Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of Titration and Optimal Dose Period [Baseline; End of Week 6 (6 Weeks)]

    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.

12. Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of the Maintenance Period [Baseline; End of Week 12 (12 Weeks)]

    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.

13. EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period. [Baseline; End of Week 6 (6 weeks)]

    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.

14. Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period. [Baseline; End of Week 6 (6 weeks)]

    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.

15. EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period [Baseline; End of Week 12 (12 weeks)]

    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.

16. Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period [Baseline; End of Week 12 (12 weeks)]

    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.

17. Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period [Baseline; End of Week 6 (6 weeks)]

    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.

18. Clinical Global Impression of Change (All Participants) at End of Maintenance Period [Baseline; End of Week 12 (12 weeks)]

    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.

19. Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline [Baseline]

    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.

20. Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period [Baseline; End of Week 6 (6 weeks)]

    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.

21. Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period [Baseline; End of Week 12 (12 Weeks)]

    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.

22. Hospital Anxiety Depression Scale: Depression Score at Baseline [Baseline]

    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.

23. Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period. [Baseline; End of Week 6 (6 weeks)]

    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.

24. Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period [Baseline; End of Week 12 (12 Weeks)]

    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.

25. Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period. [Week 6]

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

26. Participant's Satisfaction With Previous Analgesic Treatment at Baseline [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.

27. Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. [End of Week 6]

    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.

28. Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. [End of Week 8]

    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.

29. Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. [End of Week 12]

    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.

30. Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline. [Baseline]

    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".

31. NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. [End of Week 6]

    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".

32. NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period. [End of Week 12]

    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".

33. Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline. [Baseline]

    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".

34. NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. [End of Week 6]

    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".

35. NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period. [End of Week 12]

    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".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have signed an Informed Consent Form.

• Participants were men or non-pregnant, non-lactating women. Female participants must be postmenopausal, surgically sterile, or practicing an effective method of birth control. Women of childbearing potential must have a negative pregnancy test at screening.

• Participants must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain.

• Participants must be at least 18 years of age.

• Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months.

• If the participant has radicular pain, this must have been present for at least 3 months and stable for the 4 weeks before enrollment.

• Participants's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.

• Participants must report a rate of satisfaction with their previous analgesic regimen not exceeding "fair" on a subject satisfaction with treatment scale (5-point VRS).

• If under regular, daily pretreatment:

• Participants must be taking a WHO Step I or Step II analgesic medication on a daily basis for at least 2 weeks prior to the Screening Visit.

• The Investigator considers dose increase of WHO Step I analgesics (as mono- or combination therapy) and/or continuation with or dose increase of WHO Step II analgesics inadequate for the individual participant, whatever applicable.

• Participants must have an average pain intensity score (NRS 3) greater than 5 points during the last 3 days prior to the Screening Visit. or

• If no regular analgesic pretreatment is reported:

• Participants must have an average pain intensity score (NRS-3) greater than 6 points in the last 3 days prior to the Screening Visit and related to low back pain.

Exclusion Criteria:

• Presence of a clinically significant disease or laboratory findings that in the Investigator's opinion may affect efficacy or safety assessments.

• Presence of active systemic or local infection that may, in the opinion of the Investigator, affect the efficacy, quality of life/function or safety assessments.

• History of alcohol or drug abuse, or suspicion of in Investigator's judgement.

• Presence of concomitant autoimmune inflammatory conditions.

• Known history of or laboratory values reflecting severe renal impairment.

• Known history of moderately or severely impaired hepatic function.

• History of or active hepatitis B or C within the past 3 months or history of HIV infection

• History of seizure disorder or epilepsy.

• Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post-traumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness.

• Pregnant or breast-feeding.

• History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including:

• Participants with acute or severe bronchial asthma or hypercapnia.

• Participants who have or are suspected of having paralytic ileus.

• Employees of the Investigator or trial site, with direct involvement in this trial or other trials under the direction of the Investigator or trial site, as well as family members of employees of the Investigator.

• Participation in another trial concurrently or within 4 weeks prior to the Screening Visit.

• Known to or suspected of not being able to comply with the protocol and the use of the investigational medicinal product.

• Use of monoamine oxidase inhibitors within 14 days before the Screening Visit.

• Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (the doses must remain stable during the trial).

• Presence of conditions other than low back pain that could confound the assessment or self evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia.

• Any concomitant painful condition that could interfere with the subject's trial assessments or with their ability to differentiate low back pain from other painful conditions.

• Any painful procedures during the trial (e.g., major surgery) that may, in the opinion of the Investigator, affect the efficacy or safety assessments.

• Pending litigation due to chronic pain or disability.

• Intake of Step III analgesics within the 30 days prior to the Screening Visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 5	Graz		Austria
2	Site 1	Vienna		Austria
3	Site 2	Vienna		Austria
4	Site 3	Vienna		Austria
5	Site 4	Vienna		Austria
6	Site 3	Karlovac		Croatia
7	Site 2	Opatija		Croatia
8	Site 1	Sisak		Croatia
9	Site 2	Chateaugiron		France
10	Site 4	La Seyne sur Mer		France
11	Site 3	Murs Erigné		France
12	Site 1	Paris		France
13	Site 3	Berlin		Germany
14	Site 7	Böblingen		Germany
15	Site 4	Celle		Germany
16	Site 1	Dresden		Germany
17	Site 6	Hannover		Germany
18	Site 8	Leipzig		Germany
19	Site 5	Lünen		Germany
20	Site 2	Wiesbaden		Germany
21	Site 6	Bologna		Italy
22	Site 5	Catania		Italy
23	Site 2	Genova		Italy
24	Site 4	Parma		Italy
25	Site 3	Pavia		Italy
26	Site 1	Rome		Italy
27	Site 1	Lublin		Poland
28	Site 4	Tychy		Poland
29	Site 3	Wroclaw		Poland
30	Site 5	Alicante		Spain
31	Site 1	Badalona		Spain
32	Site 7	Guadalajara		Spain
33	Site 6	Madrid		Spain
34	Site 4	Oviedo		Spain
35	Site 8	Pamplona		Spain
36	Site 3	Valencia		Spain
37	Site 1	Morges		Switzerland
38	Site 2	Valens		Switzerland
39	Site 7	Belfast		United Kingdom
40	Site 2	Bristol		United Kingdom
41	Site 8	Chelmsford		United Kingdom
42	Site 6	Edinburgh		United Kingdom
43	Site 1	Glasgow		United Kingdom
44	Site 4	London		United Kingdom
45	Site 5	London		United Kingdom
46	Site 3	Plymouth		United Kingdom

Sponsors and Collaborators

• Grünenthal GmbH

Investigators

• Principal Investigator: Hans Kress, Prof. MD, Medical University / AKH Vienna

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Grünenthal GmbH
• ClinicalTrials.gov Identifier: NCT00983385
• Other Study ID Numbers: 787579; 2009-010427-12; KF5503/44
• First Posted: Sep 24, 2009
• Last Update Posted: Jan 15, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Grünenthal GmbH: low back pain; pain; assessment; tapentadol; centrally acting analgesic
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Chronic Pain; Tapentadol

Study Results

Participant Flow

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Period Title: Observation Period
STARTED	208
COMPLETED	176
NOT COMPLETED	32
Period Title: Observation Period
STARTED	176
COMPLETED	140
NOT COMPLETED	36
Period Title: Observation Period
STARTED	140
COMPLETED	117
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Overall Participants	176
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (11.8)
Sex: Female, Male (Count of Participants)
Female	111 63.1%
Male	65 36.9%
Region of Enrollment (participants) [Number]
France	14 8%
Spain	52 29.5%
Poland	11 6.3%
Austria	26 14.8%
Germany	46 26.1%
United Kingdom	12 6.8%
Switzerland	3 1.7%
Italy	12 6.8%
Prior analgesic medication (participants) [Number]
Participants pretreated with opioids	88 50%
Participants opioid naive (Step 1 analgesics)	87 49.4%
Unknown	1 0.6%

Outcome Measures

1. Primary Outcome

Title	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).
Description	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.
Time Frame	Baseline; End of Week 6 (6 Weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat. Last Observation Carried Forward (LOCF)

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	174
Mean (Standard Deviation) [Units on a scale]	-2.8 (2.12)

2. Secondary Outcome

Title	Patient Global Impression of Change at End of Titration and Optimal Dose Period
Description	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.
Time Frame	Baseline; End of Week 6 (6 Weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	134
Very much improved	12 6.8%
Much improved	55 31.3%
Minimally improved	49 27.8%
No change	10 5.7%
Minimally worse	5 2.8%
Much worse	2 1.1%
Very much worse	1 0.6%

3. Secondary Outcome

Title	Patient Global Impression of Change at End of the Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
Very much improved	19 10.8%
Much improved	42 23.9%
Minimally improved	23 13.1%
No change	5 2.8%
Minimally worse	0 0%
Much worse	0 0%
Very much worse	0 0%

4. Secondary Outcome

Title	Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT)

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	133
Physical Functioning	14.1 (17.23)
Bodily Pain	21.7 (21.39)
General Health	6.3 (16.18)
Vitality	8.0 (20.28)
Social Functioning	10.7 (25.84)
Role Emotional	14.8 (43.98)
Mental Health	7.5 (18.22)
Role Physical	25.0 (40.47)

5. Secondary Outcome

Title	Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
Physical Functioning	15.7 (21.95)
Bodily Pain	24.4 (21.96)
General Health	10.3 (14.95)
Vitality	9.5 (18.43)
Social Functioning	13.2 (27.85)
Role Emotional	18.6 (44.17)
Mental Health	12.0 (18.33)
Role Physical	29.2 (48.30)

6. Secondary Outcome

Title	painDETECT Assessment at Baseline
Description	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".
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Baseline painDETECT Negative Group	Baseline painDETECT Unclear Group	Baseline painDETECT Positive Group
Arm/Group Description	Subgroup of participants with a score between 0 and 12.	Subgroup of participants with a score between 13 and 18.	Subgroup of participants with a score between 19 and 38.
Measure Participants	49	41	81
Mean (Standard Deviation) [units on a scale]	7.1 (3.26)	13.2 (3.36)	21.4 (5.05)

7. Secondary Outcome

Title	painDETECT Assessment for Participants at End of Titration and Optimal Dose Period
Description	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".
Time Frame	End of Week 6

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Baseline painDETECT Negative Group	Baseline painDETECT Unclear Group	Baseline painDETECT Positive Group
Arm/Group Description	The subgroup of participants scoring 0-12 at the baseline painDETECT assessment were reassessed at the end of Week 6.	The subgroup of participants scoring 13-18 at the baseline painDETECT assessment were reassessed at the end of Week 6.	The subgroup of participants scoring 19-38 at the baseline painDETECT assessment were reassessed at the end of Week 6.
Measure Participants	34	32	64
Mean (Standard Deviation) [units on a scale]	5.5 (3.60)	9.8 (6.21)	14.4 (7.05)

8. Secondary Outcome

Title	painDETECT Assessment for Participants at End of the Maintenance Period
Description	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".
Time Frame	End of Week 12

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Baseline painDETECT Negative Group	Baseline painDETECT Unclear Group	Baseline painDETECT Positive Group
Arm/Group Description	The subgroup of participants scoring 0-12 at the baseline painDETECT assessment were reassessed at the end of Week 12.	The subgroup of participants scoring 13-18 at the baseline painDETECT assessment were reassessed at the end of Week 12.	The subgroup of participants scoring 19-38 at the baseline painDETECT assessment were reassessed at the end of Week 12.
Measure Participants	23	21	45
Mean (Standard Deviation) [units on a scale]	5.7 (4.22)	7.1 (6.13)	11.2 (7.52)

9. Secondary Outcome

Title	Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline
Description	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.
Time Frame	Baseline Visit

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	124
Sub-score burning pain	0.470 (0.310)
Sub-score pressing pain	0.549 (0.243)
Sub-score paroxysmal pain	0.575 (0.243)
Sub-score evoked pain	0.391 (0.263)
Sub-score paresthesia / dysthesia	0.539 (0.273)
Overall score	0.497 (0.180)

10. Secondary Outcome

Title	Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period
Description	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.
Time Frame	End of Week 6

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	97
Sub-score burning pain	0.260 (0.281)
Sub-score pressing pain	0.316 (0.257)
Sub-score paroxysmal pain	0.293 (0.258)
Sub-score evoked pain	0.230 (0.221)
Sub-score paresthesia / dysthesia	0.303 (0.2722)
Overall score	0.278 (0.204)

11. Secondary Outcome

Title	Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period
Description	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.
Time Frame	End of Week 12

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	66
Sub-score burning pain	0.180 (0.237)
Sub-score pressing pain	0.235 (0.218)
Sub-score paroxysmal pain	0.211 (0.225)
Sub-score evoked pain	0.175 (0.188)
Sub-score paresthesia / dysthesia	0.231 (0.270)
Overall score	0.206 (0.198)

12. Secondary Outcome

Title	Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of Titration and Optimal Dose Period
Description	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.
Time Frame	Baseline; End of Week 6 (6 Weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	95
Mean (Standard Deviation) [Units on a scale]	-0.224 (0.213)

13. Secondary Outcome

Title	Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of the Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 Weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	65
Mean (Standard Deviation) [units on a scale]	-0.296 (0.228)

14. Secondary Outcome

Title	EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period.
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	133
All participants	0.244 (0.315)
Participants painDETECT negative	0.229 (0.321)
Participant painDETECT unclear or positive	0.249 (0.315)

15. Secondary Outcome

Title	Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period.
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	131
All participants	12.2 (25.08)
Participants painDETECT negative	7.6 (19.74)
Participant painDETECT unclear or positive	13.8 (26.61)

16. Secondary Outcome

Title	EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
All participants	0.282 (0.297)
Participants painDETECT negative	0.182 (0.252)
Participants painDETECT unclear or positive	0.316 (0.306)

17. Secondary Outcome

Title	Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
All participants	20.0 (27.27)
Participants painDETECT negative	14.7 (26.68)
Participant painDETECT unclear or positive	21.8 (27.44)

18. Secondary Outcome

Title	Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	134
Very much improved	17 9.7%
Much improved	53 30.1%
Minimally improved	49 27.8%
No change	11 6.3%
Minimally worse	2 1.1%
Much worse	1 0.6%
Very much worse	1 0.6%

19. Secondary Outcome

Title	Clinical Global Impression of Change (All Participants) at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 weeks)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
Very much improved	17 9.7%
Much improved	45 25.6%
Minimally improved	22 12.5%
No change	5 2.8%

20. Secondary Outcome

Title	Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	173
All participants	7.8 (4.32)
Negative painDETECT participants	6.2 (4.10)
Unclear and positive painDETECT participants	8.4 (4.26)

21. Secondary Outcome

Title	Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	128
All participants	-1.2 (3.36)
Negative painDETECT participants	-0.3 (2.93)
Unclear and positive painDETECT participants	-1.5 (3.47)

22. Secondary Outcome

Title	Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 Weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
All participants	-2.1 (3.67)
Negative painDETECT participants	-0.8 (2.82)
Unclear and positive painDETECT participants	-2.5 (3.85)

23. Secondary Outcome

Title	Hospital Anxiety Depression Scale: Depression Score at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	173
All participants	7.9 (4.27)
Negative painDETECT participants	6.5 (3.96)
Unclear and positive painDETECT participants	8.5 (4.27)

24. Secondary Outcome

Title	Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period.
Description	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.
Time Frame	Baseline; End of Week 6 (6 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	128
All participants	-1.2 (3.40)
Negative painDETECT participants	-1.0 (3.15)
Unclear and positive painDETECT participants	-1.3 (3.50)

25. Secondary Outcome

Title	Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period
Description	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.
Time Frame	Baseline; End of Week 12 (12 Weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
All participants	-1.6 (3.24)
Negative painDETECT participants	-0.5 (2.86)
Unclear and positive painDETECT participants	-2.0 (3.30)

26. Secondary Outcome

Title	Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period.
Description	Tapentadol hydrochloride PR dose after 5 weeks of titration which was to be kept stable during the remained of the trial.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	59
Negative painDETECT participants	336.4 (132.90)
Unclear painDETECT participants	293.3 (103.28)
Positive painDETECT participants	268.2 (132.33)

27. Secondary Outcome

Title	Participant's Satisfaction With Previous Analgesic Treatment at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	175
Good	2 1.1%
Fair	98 55.7%
Poor	75 42.6%

28. Secondary Outcome

Title	Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period.
Description	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.
Time Frame	End of Week 6

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	134
Excellent	12 6.8%
Very Good	29 16.5%
Good	64 36.4%
Fair	22 12.5%
Poor	7 4%

29. Secondary Outcome

Title	Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period.
Description	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.
Time Frame	End of Week 8

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	122
Excellent	14 8%
Very Good	30 17%
Good	58 33%
Fair	17 9.7%
Poor	3 1.7%

30. Secondary Outcome

Title	Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period.
Description	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.
Time Frame	End of Week 12

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT).

Arm/Group Title	Tapentadol
Arm/Group Description	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.
Measure Participants	89
Excellent	10 5.7%
Very Good	38 21.6%
Good	28 15.9%
Fair	11 6.3%
Poor	2 1.1%

31. Secondary Outcome

Title	Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline.
Description	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".
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	Baseline(week -1) NRS-3 pain intensity values in PainDetect specific subgroup of participants that entered the titration and optimal dose period. 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.
Measure Participants	87
Negative painDETECT participants	7.3 (0.78)
Unclear and positive painDETECT participants	7.4 (1.00)

32. Secondary Outcome

Title	NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period.
Description	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".
Time Frame	End of Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	NRS-3 pain intensity values at End of Week 6 in PainDetect specific subgroup of participants that entered the titration and optimal dose period. 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.
Measure Participants	59
Negative painDETECT participants	4.0 (1.77)
Unclear and positive painDETECT participants	4.1 (1.86)

33. Secondary Outcome

Title	NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period.
Description	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".
Time Frame	End of Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	NRS-3 pain intensity values at End of Week 12 in PainDetect specific subgroup of participants that entered the maintenance period. 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.
Measure Participants	39
Negative painDETECT participants	3.1 (1.81)
Unclear and positive painDETECT participants	3.4 (2.32)

34. Secondary Outcome

Title	Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline.
Description	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".
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	Baseline(week -1) NRS-3 pain intensity values in PainDetect specific subgroup of participants, with prior opioid treatment, that entered the titration and optimal dose period.
Measure Participants	88
Negative painDETECT participants	6.7 (0.96)
Unclear and positive painDETECT participants	7.6 (1.07)

35. Secondary Outcome

Title	NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period.
Description	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".
Time Frame	End of Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	NRS-3 pain intensity values at end of Week 6 in painDetect specific subgroup of participants, with prior opioid treatment, that entered the titration and optimal dose period. 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.
Measure Participants	75
Negative painDETECT participants	4.2 (1.96)
Unclear and positive painDETECT participants	4.4 (2.26)

36. Secondary Outcome

Title	NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period.
Description	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".
Time Frame	End of Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol
Arm/Group Description	NRS-3 pain intensity values at End of Week 12 in painDetect specific subgroup of participants, with prior opioid treatment, that entered the maintenance period. 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.
Measure Participants	50
Negative painDETECT participants	3.4 (1.92)
Unclear and positive painDETECT participants	3.2 (1.94)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	The total daily dose of tapentadol hydrochloride PR ranged from 50 mg to 500 mg.
Arm/Group Title	Tapentadol
Arm/Group Description	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.
All Cause Mortality
	Tapentadol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tapentadol
	Affected / at Risk (%)	# Events
Total	7/176 (4%)
Hepatobiliary disorders
Cholecystitis acute	1/176 (0.6%)
Infections and infestations
Sepsis	1/176 (0.6%)
Investigations
Blood insulin abnormal	1/176 (0.6%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	1/176 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	1/176 (0.6%)
Psychiatric disorders
Confusional state	1/176 (0.6%)
Renal and urinary disorders
Renal colic	1/176 (0.6%)
Other (Not Including Serious) Adverse Events
	Tapentadol
	Affected / at Risk (%)	# Events
Total	148/176 (84.1%)
Gastrointestinal disorders
Abdominal upper pain	9/176 (5.1%)
Constipation	20/176 (11.4%)
Diarrhoea	20/176 (11.4%)
Dry mouth	27/176 (15.3%)
Nausea	37/176 (21%)
Vomiting	11/176 (6.3%)
General disorders
Fatigue	22/176 (12.5%)
Infections and infestations
Nasopharyngitis	20/176 (11.4%)
Nervous system disorders
Dizziness	31/176 (17.6%)
Headache	29/176 (16.5%)
Somnolence	18/176 (10.2%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	9/176 (5.1%)
Pruritus	9/176 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.