Pain, Chronic Pain, Low Back Pain, Neuropathic Pain, Nociceptive Pain
Conditions
Keywords
pain assessment, tapentadol, centrally acting analgesic
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 WHO Step III analgesics and show lack of tolerability. 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 (WHO Step III) with that of tapentadol hydrochloride prolonged release treatment during defined periods of evaluation.
Interventions
Participants started with 50 mg, 100 mg or 150 mg tapentadol prolonged release (PR) twice daily. Opioid rotation to tapentadol was scheduled as follows: * if less than 100 mg morphine equivalent start with 50 mg tapentadol PR; * if on 101 to 160 mg morphine equivalent daily dose start with 100 mg tapentadol PR; * if above 161 mg morphine equivalent daily dose start with 150 mg tapentadol PR. Tapentadol doses were adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis). After 5 weeks, the doses of tapentadol PR were kept stable (start of Maintenance phase). The tapentadol PR formulation was administered for up to 12 weeks. Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol PR was reached.
Sponsors
Grünenthal GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have signed an Informed Consent Form indicating that they understand the purpose of and procedures required for the trial and are willing to participate in it. * Participants are men or non-pregnant, non-lactating women. Sexually active women must be postmenopausal, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) before entry and throughout the trial. 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. * Participant's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator. * Participants must be taking a WHO Step III analgesic on a daily basis for at least 3 months prior to the Screening Visit. * Participants must have responded to the WHO Step III analgesic, i.e., participants must have a confirmed average pain intensity score (NRS 3) of ≤5 points during the last 3 days prior to the Screening Visit. * Participants must report opioid-related side effects as the reason to change their analgesic. * 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).
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: * Subjects with acute or severe bronchial asthma or hypercapnia. * Subjects 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 concomitant painful condition other than low back pain that could confound the subject's trial assessments or self evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Responded to Treatment | 6 weeks | Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment. | 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 value on the 0 to 10 scale. A negative value indicates a reduction in pain intensity from the baseline average pain intensity. |
| Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment. | Baseline; End of Week 12 (12 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 value on the 0 to 10 scale. A Negative value indicates a reduction in pain intensity from the baseline average pain intensity. |
| Patient Global Impression of Change | 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. |
| Change in the Health Survey Scores Form (SF-36) | Baseline; End of Week 6 (6 Weeks) | The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline. |
| Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Baseline | All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean for each neuropathic symptom in the sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group). |
| Mean Equipotency Ratio of Tapentadol Compared to Oxycodone | Baseline; End of Week 6 (6 Weeks) | Tapentadol was compared to Oxycodone with Oxycodone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Oxycodone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Oxycodone. |
| Average Pain Intensity Before the Start of Tapentadol Treatment | 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. |
| Mean Equipotency Ratio of Tapentadol Compared to Fentanyl | Baseline; End of Week 6 (6 Weeks) | Tapentadol was compared to Transdermal Fentanyl with Fentanyl set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Transdermal Fentanyl was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Fentanyl. |
| Mean Equipotency Ratio of Tapentadol Compared to Morphine | Baseline; End of Week 6 (6 Weeks) | Tapentadol was compared to Morphine with Morphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Morphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Morphine. |
| Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone | Baseline; End of Week 6 (6 Weeks) | Tapentadol was compared to Hydromorphone with Hydromorphone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Hydromorphone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Hydromorphone. |
| 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. |
| painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment | 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. |
| painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment | 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. |
| Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine | Baseline; End of Week 6 (6 Weeks) | Tapentadol was compared to Buprenorphine with Buprenorphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Buprenorphine. |
Countries
Belgium, Czechia, France, Germany, Netherlands, Poland, Spain, Switzerland
Participant flow
Recruitment details
The enrollment of the first participant was on the 30 October 2009 and was prematurely terminated, due to slow recruitment, on 21 January 2011 (when the last subject completed the last follow-up examination).
Pre-assignment details
The Trial had a duration of 13 weeks. The one week Observation Period did not involve dosing with Tapentadol. For Tapentadol analyses purposes the first 6 weeks of dosing with Tapentadol are reported as one period, Titration and Optimal Dose Period. The last 6 weeks on Tapentadol are reported as the Maintenance Period.
Participants by arm
| Arm | Count |
|---|---|
| Tapentadol Prolonged Release All participants started with either 50 mg, 100 mg, or 150 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted to a level that provided adequate analgesia necessary to achieve a balance between pain relief and a satisfactory level of tolerability (upwards or downwards on a weekly basis as needed). After 5 weeks the doses of tapentadol prolonged release was kept stable. Tapentadol prolonged release formulation was administered for up to 12 weeks. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol prolonged release was reached. | 125 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintenance Period | Adverse Event | 5 |
| Maintenance Period | Lack of Efficacy | 2 |
| Maintenance Period | Withdrawal by Subject | 2 |
| Observation Period | Not eligible to be dosed | 11 |
| Titration and Optimal Dose Period | Adverse Event | 15 |
| Titration and Optimal Dose Period | Lack of Efficacy | 3 |
| Titration and Optimal Dose Period | Non-Compliance | 1 |
| Titration and Optimal Dose Period | Other | 1 |
| Titration and Optimal Dose Period | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Tapentadol Prolonged Release |
|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 12 |
| Region of Enrollment Belgium | 17 participants |
| Region of Enrollment Czechia | 24 participants |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Germany | 34 participants |
| Region of Enrollment Netherlands | 14 participants |
| Region of Enrollment Poland | 9 participants |
| Region of Enrollment Spain | 21 participants |
| Region of Enrollment Switzerland | 5 participants |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 85 / 125 |
| serious Total, serious adverse events | 11 / 125 |
Outcome results
Primary
Number of Participants That Responded to Treatment
Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.
Time frame: 6 weeks
Population: Per Protocol Set. Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Number of Participants That Responded to Treatment | 76 participants |
Secondary
Average Pain Intensity Before the Start of Tapentadol Treatment
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
Population: Intention to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Average Pain Intensity Before the Start of Tapentadol Treatment | 4.8 units on a scale | Standard Deviation 0.75 |
Secondary
Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.
For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. The value indicates the change from the baseline value on the 0 to 10 scale. A Negative value indicates a reduction in pain intensity from the baseline average pain intensity.
Time frame: Baseline; End of Week 12 (12 weeks)
Population: Intention to treat (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment. | -1.3 units on a scale | Standard Deviation 2.1 |
Secondary
Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.
For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. The value indicates the change from the baseline value on the 0 to 10 scale. A negative value indicates a reduction in pain intensity from the baseline average pain intensity.
Time frame: Baseline; End of Week 6 (6 weeks)
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment. | -0.9 units on a scale | Standard Deviation 1.89 |
Secondary
Change in the Health Survey Scores Form (SF-36)
The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intention to treat (ITT).~For the sub-scores Role Emotional and Role Physical there were 98 participants, for sub-scores Physical Functioning, Vitality and Mental Health there were 99 participants, for sub-score General Health there were 100 participants with data available for the change of these sub-scores from baseline to visit 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Physical Functioning | 8.4 units on a scale | Standard Deviation 18.65 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Bodily Pain | 11.6 units on a scale | Standard Deviation 20 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | General Health | 5.9 units on a scale | Standard Deviation 15.1 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Vitality | 9.2 units on a scale | Standard Deviation 17.44 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Social Functioning | 8.0 units on a scale | Standard Deviation 24.47 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Role Emotional | -1.4 units on a scale | Standard Deviation 42.26 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Mental Health | 5.1 units on a scale | Standard Deviation 16.73 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Role Physical | 6.9 units on a scale | Standard Deviation 28.89 |
Secondary
Change in the Health Survey Scores Form (SF-36)
The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.
Time frame: Baseline; End of Week 12 (12 Weeks)
Population: Intention to Treat (ITT).~For the sub-scores Role Emotional and Role Physical, there were only 91 participants with data available for the change of these sub-scores from baseline to visit 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Role Physical | 10.7 units on a scale | Standard Deviation 31.65 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Physical Functioning | 10.5 units on a scale | Standard Deviation 19.96 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Bodily Pain | 14.1 units on a scale | Standard Deviation 22.84 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | General Health | 5.7 units on a scale | Standard Deviation 14.98 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Vitality | 12.0 units on a scale | Standard Deviation 21.03 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Social Functioning | 11.7 units on a scale | Standard Deviation 27.07 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Role Emotional | 13.9 units on a scale | Standard Deviation 43.06 |
| Tapentadol Prolonged Release | Change in the Health Survey Scores Form (SF-36) | Mental Health | 9.8 units on a scale | Standard Deviation 17.7 |
Secondary
Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine
Tapentadol was compared to Buprenorphine with Buprenorphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Buprenorphine.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intention to treat (ITT). 24 participants with previous buprenorphine treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine | 210.0 Ratio |
Secondary
Mean Equipotency Ratio of Tapentadol Compared to Fentanyl
Tapentadol was compared to Transdermal Fentanyl with Fentanyl set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Transdermal Fentanyl was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Fentanyl.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intent to treat (ITT). 22 participants with previous transdermal fentanyl treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Mean Equipotency Ratio of Tapentadol Compared to Fentanyl | 250.7 Ratio |
Secondary
Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone
Tapentadol was compared to Hydromorphone with Hydromorphone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Hydromorphone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Hydromorphone.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intention to treat (ITT). 8 participants with previous hydromorphone treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone | 10.5 Ratio |
Secondary
Mean Equipotency Ratio of Tapentadol Compared to Morphine
Tapentadol was compared to Morphine with Morphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Morphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Morphine.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intent to treat (ITT). 14 participants with previous morphine treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Mean Equipotency Ratio of Tapentadol Compared to Morphine | 3.0 Ratio |
Secondary
Mean Equipotency Ratio of Tapentadol Compared to Oxycodone
Tapentadol was compared to Oxycodone with Oxycodone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Oxycodone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Oxycodone.
Time frame: Baseline; End of Week 6 (6 Weeks)
Population: Intention to treat (ITT). 35 participants with previous oxycodone treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Mean Equipotency Ratio of Tapentadol Compared to Oxycodone | 5.3 Ratio |
Secondary
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean for each neuropathic symptom in the sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).
Time frame: Baseline
Population: Intention to treat (ITT).~For the sub-scores Overall Score and Pressing Pain there were only 69 participants with data available at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score burning pain | 0.41 units on a scale | Standard Deviation 0.284 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score pressing pain | 0.405 units on a scale | Standard Deviation 0.23 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paroxysmal pain | 0.422 units on a scale | Standard Deviation 0.221 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score evoked pain | 0.385 units on a scale | Standard Deviation 0.216 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paresthesia / dysthesia | 0.424 units on a scale | Standard Deviation 0.233 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Overall score | 0.408 units on a scale | Standard Deviation 0.158 |
Secondary
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).
Time frame: End of Week 6
Population: Intention to treat (ITT).~For the sub-scores Overall Score and Pressing Pain there were only 60 participants with data available at Visit 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score burning pain | 0.32 units on a scale | Standard Deviation 0.273 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score pressing pain | 0.322 units on a scale | Standard Deviation 0.229 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paroxysmal pain | 0.271 units on a scale | Standard Deviation 0.231 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score evoked pain | 0.274 units on a scale | Standard Deviation 0.216 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paresthesia / dysthesia | 0.302 units on a scale | Standard Deviation 0.21 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Overall score | 0.297 units on a scale | Standard Deviation 0.178 |
Secondary
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant. Results are reported as the mean (average) for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).
Time frame: End of Week 12
Population: Intention to treat (ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score burning pain | 0.27 units on a scale | Standard Deviation 0.281 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score pressing pain | 0.302 units on a scale | Standard Deviation 0.235 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paroxysmal pain | 0.254 units on a scale | Standard Deviation 0.255 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score evoked pain | 0.273 units on a scale | Standard Deviation 0.252 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Sub-score paresthesia / dysthesia | 0.299 units on a scale | Standard Deviation 0.239 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score | Overall score | 0.280 units on a scale | Standard Deviation 0.211 |
Secondary
painDETECT Assessment at 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.
Time frame: Baseline
Population: Intention to treat (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | painDETECT Assessment at Baseline | 6.5 units on a scale | Standard Deviation 3.9 |
| Baseline painDETECT Unclear Group | painDETECT Assessment at Baseline | 14.7 units on a scale | Standard Deviation 2.39 |
| Baseline painDETECT Positive Group | painDETECT Assessment at Baseline | 21.1 units on a scale | Standard Deviation 3.39 |
Secondary
painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment
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
Population: Intention to treat (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment | 6.8 units on a scale | Standard Deviation 4.85 |
| Baseline painDETECT Unclear Group | painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment | 8.6 units on a scale | Standard Deviation 5.43 |
| Baseline painDETECT Positive Group | painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment | 16.5 units on a scale | Standard Deviation 7.17 |
Secondary
painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment
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
Population: Intention to treat (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment | 7.5 units on a scale | Standard Deviation 4.18 |
| Baseline painDETECT Unclear Group | painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment | 10.5 units on a scale | Standard Deviation 4.75 |
| Baseline painDETECT Positive Group | painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment | 17.4 units on a scale | Standard Deviation 5.95 |
Secondary
Patient Global Impression of Change
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)
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Prolonged Release | Patient Global Impression of Change | Very much improved | 9 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Much improved | 34 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Minimally improved | 38 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | No change | 9 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Minimally worse | 2 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Much worse | 1 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Very much worse | 0 participants |
Secondary
Patient Global Impression of Change
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)
Population: Intention to treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Prolonged Release | Patient Global Impression of Change | Very much improved | 5 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Much improved | 29 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Minimally improved | 47 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | No change | 11 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Minimally worse | 6 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Much worse | 3 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change | Very much worse | 0 participants |