Back Pain, Low Back Pain, Neuropathic Pain
Conditions
Keywords
Severe chronic low back pain, Neuropathic pain, Constipation
Brief summary
This was a clinical effectiveness trial designed to compare the effectiveness, safety, and tolerability of treatment with tapentadol prolonged release with that of oxycodone/naloxone prolonged release in non-opioid pre-treated subjects with severe chronic low back pain with a neuropathic pain component. Both tapentadol and the opioid oxycodone are effective in chronic severe pain and tapentadol and oxycodone/naloxone have shown advantages in gastrointestinal tolerability versus oxycodone. Therefore, it was of high scientific interest to compare the latter 2 analgesics with respect to gastrointestinal tolerability. Tapentadol may have advantages regarding the neuropathic pain-related symptoms of low back pain due to its 2 mechanisms of action.
Interventions
All participants started with 50 mg tapentadol hydrochloride prolonged release (twice daily). The dose of tapentadol hydrochloride prolonged release will be adjusted in increments of 50 mg to a level that provided adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants are permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.
DRUGOxycodone/Naloxone Prolonged Release
All participants start with 10 mg/5 mg oxycodone/naloxone (twice daily). The dose of oxycodone/naloxone may be adjusted in increments of 10mg/ 5 mg oxycodone/naloxone to a level that provide adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants will be permitted a maximum dose of 50 mg/ 20 mg oxycodone/naloxone twice daily a day (100 mg/40 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent signed. * Male or female 18 years of age or older. * Women of childbearing potential must have a negative pregnancy test at the Enrollment Visit. * Women of childbearing potential must practice medically acceptable methods of birth control during the trial. * Participant must be appropriately communicative and able to differentiate with regard to location and intensity of the pain, and to complete the questionnaires used in this trial. * Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months prior to enrollment. * Participant's pain must require a strong analgesic (defined as World Health Organization Step III) as judged by the investigator. * Participants who require a washout of co-analgesics at enrolment must have an average pain score (NRS-3) of 5 points or higher. Participants who do not require a washout of co-analgesics at enrollment must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher. * The painDETECT diagnostic screening questionnaire must be either positive (score of 19 to 38 inclusive) or unclear (score of 13 to 18 inclusive). If the participant is being treated with a stable regimen of centrally acting co-analgesics, a negative painDETECT score (score 9 points or higher). Inclusion criteria prior to allocation to treatment: * Participants must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher. * Participants must score either positive (score of 19 to 38 inclusive) or unclear (score of 13 to 18 inclusive) on the painDETECT diagnostic screening questionnaire.
Exclusion criteria
* Presence of a clinically significant disease or clinical laboratory values that in the investigator's opinion may affect effectiveness, quality of life, or safety/tolerability assessments. * Presence of active systemic or local infections that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety/tolerability assessments. * 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 Enrollment Visit. * Known to or suspected of not being able to comply with the protocol and/or appropriate use of the Investigational Medicinal Products. * Any painful procedures (e.g., major surgery) scheduled during the trial duration (Enrollment Visit until Final Evaluation Visit) that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety assessments. * Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and/or if the granted benefits might be influenced by a successful participation in the trial. * Low back pain caused by cancer and/or metastatic diseases. * History of alcohol or drug abuse, or suspicion thereof in the investigator's judgment. * Presence of concomitant autoimmune inflammatory conditions. * Participants with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances. * Participants with severe renal impairment, i.e., estimated glomerular filtration rate less than 30 mL/min (according to the National Kidney Foundation 2002). * Known history of clinical laboratory values or current clinical laboratory values reflecting moderately or severely impaired hepatic function. * 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 (including brain metastases if present at the Enrollment Visit). 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 hours) or residual sequelae suggesting transient changes in consciousness. * Pregnant or breast-feeding women. * Severe respiratory depression with hypoxia and/or hypercapnia, acute or severe bronchial asthma or severe chronic obstructive pulmonary disease. * Presence or suspicion of paralytic ileus. * Participants with severe cardiac impairment, e.g., New York Heart Association class \>3, myocardial infarction less than 6 months prior to the Enrollment Visit, and/or unstable angina pectoris and/or cor pulmonale. * Participant with known history of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption. * History of allergy or hypersensitivity to tapentadol, oxycodone, naloxone, and their formulations. * Participants with acute biliary obstruction or acute pancreatitis. * Participants with hypothyroidism (including myxedema) or Addison's disease. * Participants taking any prohibited concomitant medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3) | Baseline (Randomization Visit); End of Continuation Period (Week 12) | For this pain assessment, the participant indicated the level of average pain experienced over the previous 3 days on an 11-point Numeric Rating Scale (NRS-3) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. The value reported represents the change from the randomization visit (i.e., the last 3 days in the washout period prior to Investigational Medicinal Product initiation and titration) to the end of the continuation period (i.e., up to 9 weeks on the stable dose). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline Visit). |
| Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assessed the severity of symptoms of constipation. Participants were asked How severe have each of these symptoms been in the last two weeks? e.g. Pain in your stomach. There are 3 subscales: 4 questions on abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses were rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation. The change in the assessment of constipation symptoms (PAC-SYM) total score from the Randomization Visit to the Final Evaluation Visit. The PAC-SYM overall score is the sum of scores of all non-missing items divided by the number of non-missing items (if at least 6 items were non-missing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg | Baseline (Randomization Visit); End of Continuation Period (Week 12) | Typical dermatomal pain was defined as being pain that radiates beyond the knee towards the foot (sciatica) or pain evoked by stretching of the sciatic nerve. The participant was asked to rate their pain intensity over the past 3 days with regards to this particular pain characteristic. The recalled average pain intensity over the past 3 days for the pain radiating towards or into the leg was assessed by the participant using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. |
| Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | Typical dermatomal pain was defined as being pain that radiates beyond the knee towards the foot (sciatica) or pain evoked by stretching of the sciatic nerve. Therefore, the participant was asked to rate their pain intensity over the past 3 days with regards to this particular pain characteristic. The recalled average pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. A negative sign indicates that there was a decrease in the average pain radiating towards or into the leg. |
| Worst Pain Intensity Over the Past 24 Hours | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit |
| Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit. A negative change indicates that the pain intensity decreased from the start of the trial. |
| painDETECT Final Assessment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being negative (had no neuropathic pain component). A value between 19 and 38 was rated as being positive (neuropathic component present). Values from 13 to 18 were scored as being unclear. The theoretical range of change in this trial ranged from -38 to 15. A negative change indicated a decrease in their neuropathic component of pain. |
| Change in painDETECT Final Assessment at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being negative (had no neuropathic pain component). A value between 19 and 38 was rated as being positive (neuropathic component present). Values from 13 to 18 were scored as being unclear. The theoretical range of change in this trial ranged from -38 to 15. A negative change indicated a decrease in their neuropathic component of pain. |
| Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 1. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 1. |
| Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale, from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 1. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 1. A negative change indicates that the intensity of the symptom has decreased since the start of treatment. |
| Short Form Health Survey (SF-12) | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state. |
| Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state. The change in the SF-12 score shows an improvement in health from baseline if the values are positive. The higher the value the greater the improvement since starting the trial. |
| EuroQol-5 (EQ-5D) Health Status Index Outcome | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating full health and 0 representing dead). The higher the values (the closer the value is to 1) the better the health status in a treatment group. |
| Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating full health and 0 representing dead). The higher the values (the closer the value is to 1) the better the health status in a treatment group. |
| Hospital Anxiety and Depression Scale: Anxiety | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety. A decrease in values over the trial period indicate that there has been an improvement. |
| Recalled Average Pain Intensity | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS), on this scale 0 indicates no pain and 10 indicates pain as bad as you can imagine. This scale recalls the average pain intensity during the last 3 days. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit). |
| Hospital Anxiety and Depression Scale: Depression | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. |
| Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. A negative change value indicates a decrease in the depression score since the start of treatment. |
| Patient Global Impression of Change at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | In the Patient Global Impression of Change (PGIC) the participant indicated the perceived change over the treatment period. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. |
| Clinician Global Impression of Change at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | In the Clinician Global Impression of Change (CGIC) the clinician indicated the perceived change over the treatment period. The clinician was requested to choose one of seven categories for each participant. The Clinician rated the participants change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. |
| Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep. The participant rated this categorically as being one of the following: excellent, good, fair or poor. The improvement, no change or worsening is reported based on the replies scored by the participants given at their End of Continuation Visit. |
| Sleep Evaluation: Number of Awakenings | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The participants were requested to answer the following question: How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization). |
| Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The participants were requested to answer the question: How many times did you wake up during the night? The values were calculated from the data that participants self-reported. The change from baseline in the number of times of waking up during the night in a treatment group is reported. A negative symbol indicates that there was a reduction in the number of awakenings. |
| Sleep Evaluation: Number of Hours Slept | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The participants were requested to answer the following question: How long did you sleep last night \[hours\]? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization). |
| Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The sleep evaluation questionnaire was completed by the participant. The answer was in response to the question: Sleep evaluation: How long did you sleep last night \[hours\]? The value reported is the change in the number of hours of sleep from baseline. The positive value indicates that there was an increase in the number of hours of sleep in a treatment group. |
| Sleep Evaluation: Latency (Time Taken to Fall Asleep) | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night \[hours\]? The values are for the night prior to the Randomization Visit (Baseline) and for the night prior to the Final Evaluation Visit (12 weeks after randomization). The higher the value the longer it took to fall asleep. |
| Sleep Evaluation at the End of Treatment: Change in Latency (Change in the Time Taken to Fall Asleep) | Baseline (Randomization Visit); End of Continuation Visit (Week 12) | The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night \[hours\]? The values are for the night prior to the visits. The negative change from baseline indicates that the time to falling asleep decreased from baseline in a treatment group. |
| Comparison of the Number of Participants Affected by Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | Baseline (Randomization Visit) to End of Titration Period (End of Week 3) | In this outcome measure the number of participants affected by early gastrointestinal-related treatment emergent adverse events (TEAEs). As the trial population was opioid-naïve this was considered of interest. The composition score from participant who reported: Mild, moderate to severe nausea and/or Mild, moderate to severe vomiting and/or Mild, moderate to severe constipation was evaluated. |
| Composite Event Based Comparison of Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | Baseline (Randomization Visit); End of Week 3 (End of Titration Period) | In this outcome measure the early gastrointestinal-related treatment emergent events (TEAEs) were evaluated. As the trial population was opioid-naïve this was considered of interest. The composition score of reported events of Mild, moderate to severe nausea and/or Mild, moderate to severe vomiting and/or Mild, moderate to severe constipation was evaluated. |
| Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety. A negative sign indicates that there has been a decrease in anxiety since the start of treatment. |
| Change in Recalled Average Pain Intensity at the End of Treatment | Baseline (Randomization Visit); End of Continuation Period (Week 12) | The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS), on this scale 0 indicates no pain and 10 indicates pain as bad as you can imagine. This scale recorded the average pain intensity recalled by the participant during the previous 3 days. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit). A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (baseline visit). |
Countries
Austria, Germany, Italy, Spain
Participant flow
Recruitment details
The trial started on 22 Mar 2013 with the enrollment of the first participant and was completed on 28 Jan 2014 when the last subject completed the last follow-up examination according to the protocol.
Pre-assignment details
367 participants signed informed consent. 89 participants did not meet the inclusion/exclusion criteria, 16 participants withdrew and 4 participants left the trial for other reasons. Participants randomized to oxycodone/naloxone PR could be switched to tapentadol PR treatment in the pick-up arm of the trial.
Participants by arm
| Arm | Count |
|---|---|
| Tapentadol Prolonged Release All participants started with 50 mg tapentadol prolonged release (twice daily). The dose of tapentadol prolonged release was adjusted in increments of 50 mg to a level that provided adequate analgesia. The next titration step was after a minimum of 3 days on a dose. Participants were permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). After titration participants remained on the stable dose for 9 weeks. | 130 |
| Oxycodone/Naloxone Prolonged Release All participants started with 10 mg/5 mg oxycodone/naloxone prolonged release (twice daily). The dose of oxycodone/naloxone prolonged release could be adjusted in increments of 10 mg/5 mg oxycodone/naloxone to a level that provided adequate analgesia. The next titration step was after a minimum of 3 days on a dose. Participants were permitted a maximum dose of 50 mg/20 mg oxycodone/naloxone twice daily (100 mg/40 mg total daily dose). After titration participants remained on the stable dose for 9 weeks. | 128 |
| Total | 258 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Continuation Period | Adverse Event | 8 | 4 |
| Continuation Period | Lack of Efficacy | 3 | 5 |
| Continuation Period | Lost to Follow-up | 1 | 0 |
| Continuation Period | Protocol Violation | 2 | 0 |
| Continuation Period | Technical problems | 0 | 1 |
| Continuation Period | Withdrawal by Subject | 0 | 4 |
| Pick-up Arm | Adverse Event | 9 | 0 |
| Pick-up Arm | Lack of Efficacy | 4 | 0 |
| Pick-up Arm | Technical problems | 1 | 0 |
| Pick-up Arm | Withdrawal by Subject | 1 | 0 |
| Titration Period | Adverse Event | 18 | 48 |
| Titration Period | Lack of Efficacy | 5 | 12 |
| Titration Period | Other | 1 | 0 |
| Titration Period | Protocol Violation | 0 | 1 |
| Titration Period | Technical problems | 1 | 0 |
| Titration Period | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Tapentadol Prolonged Release | Total | Oxycodone/Naloxone Prolonged Release |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 11.48 | 58.2 years STANDARD_DEVIATION 11.84 | 58.4 years STANDARD_DEVIATION 12.23 |
| Dermatol pain present | 121 participants | 232 participants | 111 participants |
| Duration of pain [months] | 61.5 months | 70.5 months | 72 months |
| Height | 168.9 centimeters STANDARD_DEVIATION 11 | 168.3 centimeters STANDARD_DEVIATION 10.38 | 167.7 centimeters STANDARD_DEVIATION 9.71 |
| Lumbar radiculopathy | 76 participants | 151 participants | 75 participants |
| painDETECT painDETECT negative | 1 participants | 5 participants | 4 participants |
| painDETECT painDETECT positive | 96 participants | 193 participants | 97 participants |
| painDETECT painDETECT unclear | 33 participants | 60 participants | 27 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 130 Participants | 258 Participants | 128 Participants |
| Region of Enrollment Austria | 8 participants | 17 participants | 9 participants |
| Region of Enrollment Germany | 102 participants | 202 participants | 100 participants |
| Region of Enrollment Spain | 20 participants | 39 participants | 19 participants |
| Sex: Female, Male Female | 77 Participants | 161 Participants | 84 Participants |
| Sex: Female, Male Male | 53 Participants | 97 Participants | 44 Participants |
| Weight | 85.3 kilogram STANDARD_DEVIATION 18.23 | 83.5 kilogram STANDARD_DEVIATION 18.39 | 81.6 kilogram STANDARD_DEVIATION 18.43 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 97 / 130 | 105 / 128 | 29 / 50 |
| serious Total, serious adverse events | 3 / 130 | 2 / 128 | 0 / 50 |
Outcome results
Primary
Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3)
For this pain assessment, the participant indicated the level of average pain experienced over the previous 3 days on an 11-point Numeric Rating Scale (NRS-3) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. The value reported represents the change from the randomization visit (i.e., the last 3 days in the washout period prior to Investigational Medicinal Product initiation and titration) to the end of the continuation period (i.e., up to 9 weeks on the stable dose). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline Visit).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: The primary analysis was performed for the Per Protocol Set (PPS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3) | -3.7 units on a scale | Standard Error 0.25 |
| Oxycodone/Naloxone Prolonged Release | Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3) | -2.7 units on a scale | Standard Error 0.26 |
Primary
Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score
The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assessed the severity of symptoms of constipation. Participants were asked How severe have each of these symptoms been in the last two weeks? e.g. Pain in your stomach. There are 3 subscales: 4 questions on abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses were rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation. The change in the assessment of constipation symptoms (PAC-SYM) total score from the Randomization Visit to the Final Evaluation Visit. The PAC-SYM overall score is the sum of scores of all non-missing items divided by the number of non-missing items (if at least 6 items were non-missing).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: The primary analysis was performed for the Per Protocol Set (PPS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score | 0.07 units on a scale | Standard Error 0.06 |
| Oxycodone/Naloxone Prolonged Release | Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score | 0.14 units on a scale | Standard Error 0.062 |
Secondary
Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg
Typical dermatomal pain was defined as being pain that radiates beyond the knee towards the foot (sciatica) or pain evoked by stretching of the sciatic nerve. The participant was asked to rate their pain intensity over the past 3 days with regards to this particular pain characteristic. The recalled average pain intensity over the past 3 days for the pain radiating towards or into the leg was assessed by the participant using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg | Baseline | 7.5 units on a scale | Standard Deviation 1.25 |
| Tapentadol Prolonged Release | Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg | End of Continuation Period | 3.7 units on a scale | Standard Deviation 2.76 |
| Oxycodone/Naloxone Prolonged Release | Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg | Baseline | 7.6 units on a scale | Standard Deviation 1.05 |
| Oxycodone/Naloxone Prolonged Release | Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg | End of Continuation Period | 4.7 units on a scale | Standard Deviation 2.52 |
Secondary
Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment
The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating full health and 0 representing dead). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment | 0.3395 units on a scale | Standard Error 0.02785 |
| Oxycodone/Naloxone Prolonged Release | Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment | 0.2398 units on a scale | Standard Error 0.02811 |
Secondary
Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety. A negative sign indicates that there has been a decrease in anxiety since the start of treatment.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety | -2.1 units on a scale | Standard Error 0.34 |
| Oxycodone/Naloxone Prolonged Release | Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety | -1.1 units on a scale | Standard Error 0.35 |
Secondary
Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. A negative change value indicates a decrease in the depression score since the start of treatment.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last observation carried forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression | -2.4 units on a scale | Standard Error 0.34 |
| Oxycodone/Naloxone Prolonged Release | Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression | -1.1 units on a scale | Standard Error 0.36 |
Secondary
Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment
In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale, from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 1. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 1. A negative change indicates that the intensity of the symptom has decreased since the start of treatment.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Overall Score | -0.353 units on a scale | Standard Error 0.0208 |
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Burning Pain | -0.375 units on a scale | Standard Error 0.0249 |
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Pressing Pain | -0.331 units on a scale | Standard Error 0.0235 |
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Paroxysmal Pain | -0.385 units on a scale | Standard Error 0.0246 |
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-score Evoked Pain | -0.334 units on a scale | Standard Error 0.0222 |
| Tapentadol Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Pare/Dysesthesia | -0.363 units on a scale | Standard Error 0.0229 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-score Evoked Pain | -0.225 units on a scale | Standard Error 0.0225 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Overall Score | -0.248 units on a scale | Standard Error 0.0211 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Paroxysmal Pain | -0.283 units on a scale | Standard Error 0.025 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Burning Pain | -0.278 units on a scale | Standard Error 0.0252 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Pare/Dysesthesia | -0.252 units on a scale | Standard Error 0.0231 |
| Oxycodone/Naloxone Prolonged Release | Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment | Sub-Score Pressing Pain | -0.226 units on a scale | Standard Error 0.0238 |
Secondary
Change in painDETECT Final Assessment at the End of Treatment
The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being negative (had no neuropathic pain component). A value between 19 and 38 was rated as being positive (neuropathic component present). Values from 13 to 18 were scored as being unclear. The theoretical range of change in this trial ranged from -38 to 15. A negative change indicated a decrease in their neuropathic component of pain.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in painDETECT Final Assessment at the End of Treatment | -10.8 units on a scale | Standard Error 0.67 |
| Oxycodone/Naloxone Prolonged Release | Change in painDETECT Final Assessment at the End of Treatment | -7.9 units on a scale | Standard Error 0.69 |
Secondary
Change in Recalled Average Pain Intensity at the End of Treatment
The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS), on this scale 0 indicates no pain and 10 indicates pain as bad as you can imagine. This scale recorded the average pain intensity recalled by the participant during the previous 3 days. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit). A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (baseline visit).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Recalled Average Pain Intensity at the End of Treatment | -3.7 units on a scale | Standard Error 0.24 |
| Oxycodone/Naloxone Prolonged Release | Change in Recalled Average Pain Intensity at the End of Treatment | -2.8 units on a scale | Standard Error 0.24 |
Secondary
Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment
The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit. A negative change indicates that the pain intensity decreased from the start of the trial.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment | -3.7 units on a scale | Standard Error 0.25 |
| Oxycodone/Naloxone Prolonged Release | Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment | -2.8 units on a scale | Standard Error 0.25 |
Secondary
Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment
Typical dermatomal pain was defined as being pain that radiates beyond the knee towards the foot (sciatica) or pain evoked by stretching of the sciatic nerve. Therefore, the participant was asked to rate their pain intensity over the past 3 days with regards to this particular pain characteristic. The recalled average pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. A negative sign indicates that there was a decrease in the average pain radiating towards or into the leg.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment | -3.9 units on a scale | Standard Error 0.25 |
| Oxycodone/Naloxone Prolonged Release | Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment | -2.8 units on a scale | Standard Error 0.25 |
Secondary
Changes in the Short Form Health Survey (SF-12) at the End of Treatment
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state. The change in the SF-12 score shows an improvement in health from baseline if the values are positive. The higher the value the greater the improvement since starting the trial.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS), Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Physical Functioning | 8.358 units on a scale | Standard Error 0.8262 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Role-Physical | 7.260 units on a scale | Standard Error 0.7115 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Bodily Pain | 10.990 units on a scale | Standard Error 0.9462 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | General Health | 8.447 units on a scale | Standard Error 0.8702 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Vitality | 4.943 units on a scale | Standard Error 0.8062 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Social Functioning | 5.246 units on a scale | Standard Error 0.887 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Role-Emotional | 4.764 units on a scale | Standard Error 0.9472 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Mental Health | 5.158 units on a scale | Standard Error 0.8386 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Physical Component Summary | 9.735 units on a scale | Standard Error 0.7948 |
| Tapentadol Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Mental Component Summary | 3.077 units on a scale | Standard Error 0.8457 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Mental Health | 2.973 units on a scale | Standard Error 0.8575 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Physical Functioning | 5.073 units on a scale | Standard Error 0.8361 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Social Functioning | 2.286 units on a scale | Standard Error 0.8997 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Role-Physical | 4.668 units on a scale | Standard Error 0.7224 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Mental Component Summary | 1.146 units on a scale | Standard Error 0.8679 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Bodily Pain | 7.458 units on a scale | Standard Error 0.957 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Role-Emotional | 2.587 units on a scale | Standard Error 0.9807 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | General Health | 4.309 units on a scale | Standard Error 0.8818 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Physical Component Summary | 6.202 units on a scale | Standard Error 0.8058 |
| Oxycodone/Naloxone Prolonged Release | Changes in the Short Form Health Survey (SF-12) at the End of Treatment | Vitality | 1.468 units on a scale | Standard Error 0.8179 |
Secondary
Clinician Global Impression of Change at the End of Treatment
In the Clinician Global Impression of Change (CGIC) the clinician indicated the perceived change over the treatment period. The clinician was requested to choose one of seven categories for each participant. The Clinician rated the participants change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Minimally Improved | 22 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Minimally Worse | 6 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Much Improved | 44 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Much Worse | 3 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | No Change | 21 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Very Much Worse | 0 participants |
| Tapentadol Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Very Much Improved | 32 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Very Much Worse | 1 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Very Much Improved | 18 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Much Improved | 25 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Minimally Improved | 37 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | No Change | 26 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Minimally Worse | 7 participants |
| Oxycodone/Naloxone Prolonged Release | Clinician Global Impression of Change at the End of Treatment | Much Worse | 9 participants |
Secondary
Comparison of the Number of Participants Affected by Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids
In this outcome measure the number of participants affected by early gastrointestinal-related treatment emergent adverse events (TEAEs). As the trial population was opioid-naïve this was considered of interest. The composition score from participant who reported: Mild, moderate to severe nausea and/or Mild, moderate to severe vomiting and/or Mild, moderate to severe constipation was evaluated.
Time frame: Baseline (Randomization Visit) to End of Titration Period (End of Week 3)
Population: Safety Set (SAF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Comparison of the Number of Participants Affected by Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | 42 participants |
| Oxycodone/Naloxone Prolonged Release | Comparison of the Number of Participants Affected by Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | 59 participants |
Secondary
Composite Event Based Comparison of Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids
In this outcome measure the early gastrointestinal-related treatment emergent events (TEAEs) were evaluated. As the trial population was opioid-naïve this was considered of interest. The composition score of reported events of Mild, moderate to severe nausea and/or Mild, moderate to severe vomiting and/or Mild, moderate to severe constipation was evaluated.
Time frame: Baseline (Randomization Visit); End of Week 3 (End of Titration Period)
Population: Safety Set (SAF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol Prolonged Release | Composite Event Based Comparison of Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | 56 number of events |
| Oxycodone/Naloxone Prolonged Release | Composite Event Based Comparison of Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids | 81 number of events |
Secondary
EuroQol-5 (EQ-5D) Health Status Index Outcome
The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating full health and 0 representing dead). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | EuroQol-5 (EQ-5D) Health Status Index Outcome | Baseline | 0.3186 units on a scale | Standard Deviation 0.29464 |
| Tapentadol Prolonged Release | EuroQol-5 (EQ-5D) Health Status Index Outcome | End of Continuation Period | 0.6686 units on a scale | Standard Deviation 0.31683 |
| Oxycodone/Naloxone Prolonged Release | EuroQol-5 (EQ-5D) Health Status Index Outcome | Baseline | 0.3392 units on a scale | Standard Deviation 0.31134 |
| Oxycodone/Naloxone Prolonged Release | EuroQol-5 (EQ-5D) Health Status Index Outcome | End of Continuation Period | 0.5745 units on a scale | Standard Deviation 0.31378 |
Secondary
Hospital Anxiety and Depression Scale: Anxiety
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety. A decrease in values over the trial period indicate that there has been an improvement.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Hospital Anxiety and Depression Scale: Anxiety | Baseline | 7.3 units on a scale | Standard Deviation 4.06 |
| Tapentadol Prolonged Release | Hospital Anxiety and Depression Scale: Anxiety | End of Continuation Period | 5.3 units on a scale | Standard Deviation 4.4 |
| Oxycodone/Naloxone Prolonged Release | Hospital Anxiety and Depression Scale: Anxiety | Baseline | 8.2 units on a scale | Standard Deviation 4.28 |
| Oxycodone/Naloxone Prolonged Release | Hospital Anxiety and Depression Scale: Anxiety | End of Continuation Period | 6.7 units on a scale | Standard Deviation 4.58 |
Secondary
Hospital Anxiety and Depression Scale: Depression
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last observation carried forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Hospital Anxiety and Depression Scale: Depression | Baseline | 7.4 units on a scale | Standard Deviation 4.08 |
| Tapentadol Prolonged Release | Hospital Anxiety and Depression Scale: Depression | End of Continuation Period | 5.1 units on a scale | Standard Deviation 4.17 |
| Oxycodone/Naloxone Prolonged Release | Hospital Anxiety and Depression Scale: Depression | Baseline | 8.0 units on a scale | Standard Deviation 4.08 |
| Oxycodone/Naloxone Prolonged Release | Hospital Anxiety and Depression Scale: Depression | End of Continuation Period | 6.5 units on a scale | Standard Deviation 4.86 |
Secondary
Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment
In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 1. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 1.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-score pressing pain | 0.595 units on a scale | Standard Deviation 0.2523 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Pressing Pain | 0.276 units on a scale | Standard Deviation 0.265 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Paroxysmal Pain | 0.638 units on a scale | Standard Deviation 0.2312 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Evoked Pain | 0.555 units on a scale | Standard Deviation 0.2536 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Overall Score | 0.598 units on a scale | Standard Deviation 0.1769 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Paroxysmal Pain | 0.269 units on a scale | Standard Deviation 0.2716 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Overall Score | 0.251 units on a scale | Standard Deviation 0.2344 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Burning Pain | 0.612 units on a scale | Standard Deviation 0.2569 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Burning Pain | 0.248 units on a scale | Standard Deviation 0.2767 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Evoked Pain | 0.219 units on a scale | Standard Deviation 0.252 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Pare/Dysesthesia | 0.621 units on a scale | Standard Deviation 0.2292 |
| Tapentadol Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Pare/Dysesthesia | 0.260 units on a scale | Standard Deviation 0.2656 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Pare/Dysesthesia | 0.642 units on a scale | Standard Deviation 0.1809 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-score pressing pain | 0.608 units on a scale | Standard Deviation 0.1848 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Overall Score | 0.354 units on a scale | Standard Deviation 0.2334 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Pressing Pain | 0.375 units on a scale | Standard Deviation 0.2645 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Evoked Pain | 0.321 units on a scale | Standard Deviation 0.2554 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Paroxysmal Pain | 0.670 units on a scale | Standard Deviation 0.172 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Paroxysmal Pain | 0.375 units on a scale | Standard Deviation 0.2673 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Burning Pain | 0.634 units on a scale | Standard Deviation 0.2279 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Sub-Score Evoked Pain | 0.548 units on a scale | Standard Deviation 0.23 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Pare/Dysesthesia | 0.372 units on a scale | Standard Deviation 0.2615 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | End Continuation Period Sub-Score Burning Pain | 0.337 units on a scale | Standard Deviation 0.2758 |
| Oxycodone/Naloxone Prolonged Release | Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment | Baseline Overall Score | 0.612 units on a scale | Standard Deviation 0.1445 |
Secondary
painDETECT Final Assessment
The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being negative (had no neuropathic pain component). A value between 19 and 38 was rated as being positive (neuropathic component present). Values from 13 to 18 were scored as being unclear. The theoretical range of change in this trial ranged from -38 to 15. A negative change indicated a decrease in their neuropathic component of pain.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | painDETECT Final Assessment | Baseline | 22.3 units on a scale | Standard Deviation 5.25 |
| Tapentadol Prolonged Release | painDETECT Final Assessment | End of Continuation Period | 11.9 units on a scale | Standard Deviation 7.76 |
| Oxycodone/Naloxone Prolonged Release | painDETECT Final Assessment | Baseline | 22.5 units on a scale | Standard Deviation 4.79 |
| Oxycodone/Naloxone Prolonged Release | painDETECT Final Assessment | End of Continuation Period | 14.6 units on a scale | Standard Deviation 7.37 |
Secondary
Patient Global Impression of Change at the End of Treatment
In the Patient Global Impression of Change (PGIC) the participant indicated the perceived change over the treatment period. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Minimally Improved | 32 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Minimally Worse | 3 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Much Improved | 43 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Much Worse | 2 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | No Change | 21 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Very Much Worse | 1 participants |
| Tapentadol Prolonged Release | Patient Global Impression of Change at the End of Treatment | Very Much Improved | 27 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Very Much Worse | 3 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Very Much Improved | 18 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Much Improved | 19 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Minimally Improved | 46 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | No Change | 29 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Minimally Worse | 6 participants |
| Oxycodone/Naloxone Prolonged Release | Patient Global Impression of Change at the End of Treatment | Much Worse | 4 participants |
Secondary
Recalled Average Pain Intensity
The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS), on this scale 0 indicates no pain and 10 indicates pain as bad as you can imagine. This scale recalls the average pain intensity during the last 3 days. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Recalled Average Pain Intensity | Baseline | 7.7 units on a scale | Standard Deviation 1.04 |
| Tapentadol Prolonged Release | Recalled Average Pain Intensity | End of Continuation Period | 3.9 units on a scale | Standard Deviation 2.68 |
| Oxycodone/Naloxone Prolonged Release | Recalled Average Pain Intensity | Baseline | 7.6 units on a scale | Standard Deviation 0.95 |
| Oxycodone/Naloxone Prolonged Release | Recalled Average Pain Intensity | End of Continuation Period | 4.8 units on a scale | Standard Deviation 2.43 |
Secondary
Short Form Health Survey (SF-12)
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Role-Physical | 33.783 units on a scale | Standard Deviation 6.501 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Social Functioning | 42.290 units on a scale | Standard Deviation 10.5832 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Bodily Pain | 42.003 units on a scale | Standard Deviation 10.1964 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Social Functioning | 47.494 units on a scale | Standard Deviation 10.4657 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Physical functioning | 41.701 units on a scale | Standard Deviation 10.2556 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Role-Emotional | 41.018 units on a scale | Standard Deviation 13.0098 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline General Health | 36.110 units on a scale | Standard Deviation 8.3196 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Role-Emotional | 44.727 units on a scale | Standard Deviation 12.139 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Role-Physical | 41.025 units on a scale | Standard Deviation 8.7602 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Mental Health | 44.967 units on a scale | Standard Deviation 9.2036 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period General Health | 44.382 units on a scale | Standard Deviation 10.3772 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Mental health | 49.828 units on a scale | Standard Deviation 10.3896 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Physical Functioning | 33.256 units on a scale | Standard Deviation 7.7695 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Physical Component summary | 30.319 units on a scale | Standard Deviation 7.2739 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Vitality | 46.518 units on a scale | Standard Deviation 8.5121 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Physical component summary | 40.493 units on a scale | Standard Deviation 9.3352 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Bodily Pain | 30.430 units on a scale | Standard Deviation 7.9923 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | Baseline Mental Component Summary | 48.736 units on a scale | Standard Deviation 11.5697 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Vitality | 51.202 units on a scale | Standard Deviation 9.3262 |
| Tapentadol Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Mental Component Summary | 51.117 units on a scale | Standard Deviation 11.0365 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Vitality | 47.724 units on a scale | Standard Deviation 10.0303 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Physical Functioning | 33.813 units on a scale | Standard Deviation 6.8734 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Physical functioning | 39.120 units on a scale | Standard Deviation 9.4634 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Role-Physical | 33.695 units on a scale | Standard Deviation 6.2586 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Role-Physical | 38.757 units on a scale | Standard Deviation 7.6342 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Bodily Pain | 31.117 units on a scale | Standard Deviation 8.1434 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Bodily Pain | 38.637 units on a scale | Standard Deviation 10.3872 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline General Health | 34.652 units on a scale | Standard Deviation 7.0912 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period General Health | 39.941 units on a scale | Standard Deviation 10.1717 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Vitality | 45.516 units on a scale | Standard Deviation 8.0387 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Mental Component Summary | 47.595 units on a scale | Standard Deviation 11.4544 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Social Functioning | 41.734 units on a scale | Standard Deviation 9.8674 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Social Functioning | 44.475 units on a scale | Standard Deviation 10.5281 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Role-Emotional | 37.046 units on a scale | Standard Deviation 13.2164 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Role-Emotional | 41.219 units on a scale | Standard Deviation 12.789 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Mental Health | 42.394 units on a scale | Standard Deviation 9.1589 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Mental health | 46.451 units on a scale | Standard Deviation 10.3372 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Physical Component summary | 31.684 units on a scale | Standard Deviation 6.8313 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | End Continuation Period Physical component summary | 37.765 units on a scale | Standard Deviation 8.8375 |
| Oxycodone/Naloxone Prolonged Release | Short Form Health Survey (SF-12) | Baseline Mental Component Summary | 45.216 units on a scale | Standard Deviation 11.7462 |
Secondary
Sleep Evaluation at the End of Treatment: Change in Latency (Change in the Time Taken to Fall Asleep)
The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night \[hours\]? The values are for the night prior to the visits. The negative change from baseline indicates that the time to falling asleep decreased from baseline in a treatment group.
Time frame: Baseline (Randomization Visit); End of Continuation Visit (Week 12)
Population: Full Analysis Set (FAS). Last Observation carried Forward (LOCF). Number of participants taken into account for the analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in Latency (Change in the Time Taken to Fall Asleep) | -0.300 hours | Standard Error 0.1 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in Latency (Change in the Time Taken to Fall Asleep) | -0.177 hours | Standard Error 0.1025 |
Secondary
Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings
The participants were requested to answer the question: How many times did you wake up during the night? The values were calculated from the data that participants self-reported. The change from baseline in the number of times of waking up during the night in a treatment group is reported. A negative symbol indicates that there was a reduction in the number of awakenings.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings | -0.8 number of awakenings | Standard Error 0.15 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings | -0.5 number of awakenings | Standard Error 0.16 |
Secondary
Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept
The sleep evaluation questionnaire was completed by the participant. The answer was in response to the question: Sleep evaluation: How long did you sleep last night \[hours\]? The value reported is the change in the number of hours of sleep from baseline. The positive value indicates that there was an increase in the number of hours of sleep in a treatment group.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept | 0.460 hours | Standard Error 0.1714 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept | 0.412 hours | Standard Error 0.1763 |
Secondary
Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep. The participant rated this categorically as being one of the following: excellent, good, fair or poor. The improvement, no change or worsening is reported based on the replies scored by the participants given at their End of Continuation Visit.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Improvement | 62 participants |
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | No Change | 46 participants |
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Worsening | 16 participants |
| Tapentadol Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Missing | 6 participants |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Missing | 12 participants |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Improvement | 43 participants |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | Worsening | 15 participants |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep | No Change | 56 participants |
Secondary
Sleep Evaluation: Latency (Time Taken to Fall Asleep)
The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night \[hours\]? The values are for the night prior to the Randomization Visit (Baseline) and for the night prior to the Final Evaluation Visit (12 weeks after randomization). The higher the value the longer it took to fall asleep.
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation: Latency (Time Taken to Fall Asleep) | Baseline | 1.047 hours | Standard Deviation 1.1746 |
| Tapentadol Prolonged Release | Sleep Evaluation: Latency (Time Taken to Fall Asleep) | End of Continuation Period | 0.803 hours | Standard Deviation 1.1154 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Latency (Time Taken to Fall Asleep) | Baseline | 1.203 hours | Standard Deviation 1.3029 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Latency (Time Taken to Fall Asleep) | End of Continuation Period | 0.865 hours | Standard Deviation 1.0301 |
Secondary
Sleep Evaluation: Number of Awakenings
The participants were requested to answer the following question: How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation: Number of Awakenings | Baseline | 3.0 number of awakenings | Standard Deviation 2.8 |
| Tapentadol Prolonged Release | Sleep Evaluation: Number of Awakenings | End of Continuation Period | 2.0 number of awakenings | Standard Deviation 1.66 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Number of Awakenings | Baseline | 2.6 number of awakenings | Standard Deviation 1.67 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Number of Awakenings | End of Continuation Period | 2.2 number of awakenings | Standard Deviation 1.65 |
Secondary
Sleep Evaluation: Number of Hours Slept
The participants were requested to answer the following question: How long did you sleep last night \[hours\]? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization).
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Sleep Evaluation: Number of Hours Slept | Baseline | 5.781 hours | Standard Deviation 1.5908 |
| Tapentadol Prolonged Release | Sleep Evaluation: Number of Hours Slept | End of Continuation Period | 6.207 hours | Standard Deviation 1.8007 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Number of Hours Slept | Baseline | 5.675 hours | Standard Deviation 1.7118 |
| Oxycodone/Naloxone Prolonged Release | Sleep Evaluation: Number of Hours Slept | End of Continuation Period | 6.218 hours | Standard Deviation 1.8426 |
Secondary
Worst Pain Intensity Over the Past 24 Hours
The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. The participant was asked: Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit
Time frame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Population: Full Analysis Set (FAS). Last Observation Carried Forward (LOCF). Number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Worst Pain Intensity Over the Past 24 Hours | Baseline | 8.1 units on a scale | Standard Deviation 1.03 |
| Tapentadol Prolonged Release | Worst Pain Intensity Over the Past 24 Hours | End of Continuation Period | 4.3 units on a scale | Standard Deviation 2.73 |
| Oxycodone/Naloxone Prolonged Release | Worst Pain Intensity Over the Past 24 Hours | End of Continuation Period | 5.2 units on a scale | Standard Deviation 2.5 |
| Oxycodone/Naloxone Prolonged Release | Worst Pain Intensity Over the Past 24 Hours | Baseline | 8.0 units on a scale | Standard Deviation 1.06 |