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

Study Overview
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Brief Summary
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The main objective of the study is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride prolonged release in subjects suffering from severe chronic low back pain (LBP) who are taking either WHO Step I or Step II analgesics or no regular analgesics. This is a clinical effectiveness trial designed to establish a link between anticipated clinical outcomes and the clinical practice by means of selected measures of clinical and subject-reported outcome. The trial will compare the effectiveness of previous analgesic treatment (either WHO Step I or Step II analgesics or no regular analgesics) with that of tapentadol hydrochloride prolonged release (PR) treatment during defined periods of evaluation.

Official Title
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An Evaluation of the Effectiveness and Tolerability of Tapentadol Hydrochloride Prolonged Release, and Tapentadol Hydrochloride Immediate Release on Demand, in Subjects With Uncontrolled Severe Chronic Nociceptive, Mixed or Neuropathic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics.

Conditions
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Chronic Pain, Low Back Pain

Intervention / Treatment
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* Drug: Tapentadol PR
* Other: Observation period
* Drug: Tapentadol PR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have signed an Informed Consent Form. Participants were men or non-pregnant, non-lactating women. Female participants must be postmenopausal, surgically sterile, or practicing an effective method of birth control. Women of childbearing potential must have a negative pregnancy test at screening. Participants must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain. Participants must be at least 18 years of age. Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months. If the participant has radicular pain, this must have been present for at least 3 months and stable for the 4 weeks before enrollment. Participants's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator. Participants must report a rate of satisfaction with their previous analgesic regimen not exceeding fair on a subject satisfaction with treatment scale (5-point VRS). If under regular, daily pretreatment: Participants must be taking a WHO Step I or Step II analgesic medication on a daily basis for at least 2 weeks prior to the Screening Visit. The Investigator considers dose increase of WHO Step I analgesics (as mono- or combination therapy) and/or continuation with or dose increase of WHO Step II analgesics inadequate for the individual participant, whatever applicable. Participants must have an average pain intensity score (NRS 3) greater than 5 points during the last 3 days prior to the Screening Visit. or If no regular analgesic pretreatment is reported: Participants must have an average pain intensity score (NRS-3) greater than 6 points in the last 3 days prior to the Screening Visit and related to low back pain. Exclusion Criteria: Presence of a clinically significant disease or laboratory findings that in the Investigator's opinion may affect efficacy or safety assessments. Presence of active systemic or local infection that may, in the opinion of the Investigator, affect the efficacy, quality of life/function or safety assessments. History of alcohol or drug abuse, or suspicion of in Investigator's judgement. Presence of concomitant autoimmune inflammatory conditions. Known history of or laboratory values reflecting severe renal impairment. Known history of moderately or severely impaired hepatic function. History of or active hepatitis B or C within the past 3 months or history of HIV infection History of seizure disorder or epilepsy. Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post-traumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness. Pregnant or breast-feeding. History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including: Participants with acute or severe bronchial asthma or hypercapnia. Participants who have or are suspected of having paralytic ileus. Employees of the Investigator or trial site, with direct involvement in this trial or other trials under the direction of the Investigator or trial site, as well as family members of employees of the Investigator. Participation in another trial concurrently or within 4 weeks prior to the Screening Visit. Known to or suspected of not being able to comply with the protocol and the use of the investigational medicinal product. Use of monoamine oxidase inhibitors within 14 days before the Screening Visit. Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (the doses must remain stable during the trial). Presence of conditions other than low back pain that could confound the assessment or self evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia. Any concomitant painful condition that could interfere with the subject's trial assessments or with their ability to differentiate low back pain from other painful conditions. Any painful procedures during the trial (e.g., major surgery) that may, in the opinion of the Investigator, affect the efficacy or safety assessments. Pending litigation due to chronic pain or disability. Intake of Step III analgesics within the 30 days prior to the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol<br>Tapentadol PR was given orally twice a day. A maximum of 2 oral Tapentadol immediate release (IR) tablets per day, with a minimum of a 4 hour interval between doses, were taken if there were acute pain episodes. The total daily dose of Tapentadol PR and IR were not permitted to exceed 500 mg per day. | Drug: Tapentadol PR<br>* Tapentadol Prolonged Release (PR) Titration and Optimal Dose Period: Starting at 50 mg Tapentadol PR twice daily, adjusted with 50 mg PR steps (upwards or downwards) as necessary to achieve a balance between pain relief and a satisfactory level of tolerability. Participants were not permitted to exceed a dose of 500 mg of Tapentadol per day.<br>* Other names: Nucynta®;Other: Observation period<br>* Eligibility assessment period to characterize the baseline over a one week period (week -1). Participants continued their previous treatment prior to allocation to tapentadol, if eligible.<br>Drug: Tapentadol PR<br>* Maintenance Period: In this period participants continued Tapentadol Prolonged Release (PR) on the dose established in the Titration and Optimal Dose Period. Tapentadol IR participants were not permitted to exceed a total daily tapentadol dose of 500 mg.<br>* Other names: Nucynta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Endpoint is Defined as the Change of the Average Pain Intensity Score on an 11-point NRS-3 at Week 6 From Week -1 (Baseline). | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. The value indicates the change from the baseline participant assessment on the 0 to 10 scale. A negative value indicates a reduction in pain intensity. | Baseline; End of Week 6 (6 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change at End of Titration and Optimal Dose Period | In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse. | Baseline; End of Week 6 (6 Weeks) | 
| Patient Global Impression of Change at End of the Maintenance Period | In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse. | Baseline; End of Week 12 (12 weeks) | 
| Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period | The Scores Form 36 (SF-36) includes several brief board questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline. | Baseline; End of Week 6 (6 weeks) | 
| Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period | The Scores Form 36 (SF-36) includes several brief board questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline. | Baseline; End of Week 12 (12 weeks) | 
| painDETECT Assessment at Baseline | The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being negative (no neuropathic pain component). Value between 19 and 38 as being positive (presence of neuropathic component). Values from 13 to 18 are scored as being unclear. | Baseline | 
| painDETECT Assessment for Participants at End of Titration and Optimal Dose Period | The baseline painDETECT score was reassessed at the end of Week 6. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being negative (no neuropathic pain component). Value between 19 and 38 as being positive (presence of neuropathic component). Values from 13 to 18 are scored as being unclear. | End of Week 6 | 
| painDETECT Assessment for Participants at End of the Maintenance Period | The baseline painDETECT score was reassessed at the end of Week 12. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being negative (no neuropathic pain component). Value between 19 and 38 as being positive (presence of neuropathic component). Values from 13 to 18 are scored as being unclear. | End of Week 12 | 
| Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline | Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales. | Baseline Visit | 
| Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period | Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales. | End of Week 6 | 
| Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period | Mean score NPSI (Neuropathic Pain Symptom Inventory). The participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales. | End of Week 12 | 
| Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of Titration and Optimal Dose Period | Change in mean score NPSI, questionnaire evaluates symptoms of neuropathic pain. Ten pain descriptors questions are answered on an 11-point scale 0 (no pain)-10 (most intense pain imaginable). The NPSI derives a total intensity score calculated from the subscores. A negative value indicates improvement in neuropathic symptoms. | Baseline; End of Week 6 (6 Weeks) | 
| Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of the Maintenance Period | Change in mean score NPSI, questionnaire evaluates symptoms of neuropathic pain. Ten pain descriptors questions are answered on an 11-point scale 0 (no pain)-10 (most intense pain imaginable). The NPSI derives a total intensity score calculated from the subscores. A negative value indicates improvement in neuropathic symptoms. | Baseline; End of Week 12 (12 Weeks) | 
| EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period. | The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating full health and 0 representing dead. The positive values indicate that during the study the health status improved. | Baseline; End of Week 6 (6 weeks) | 
| Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period. | EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement. | Baseline; End of Week 6 (6 weeks) | 
| EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period | The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating full health and 0 representing dead. The positive values indicate that during the study the health status improved. | Baseline; End of Week 12 (12 weeks) | 
| Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period | EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement. | Baseline; End of Week 12 (12 weeks) | 
| Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period | In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change over the treatment period. The clinician is requested to choose one of seven categories. Scores range from very much improved to very much worse. | Baseline; End of Week 6 (6 weeks) | 
| Clinical Global Impression of Change (All Participants) at End of Maintenance Period | In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change over the treatment period. The clinician is requested to choose one of seven categories. Scores range from very much improved to very much worse. | Baseline; End of Week 12 (12 weeks) | 
| Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline | Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline | 
| Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period | Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline; End of Week 6 (6 weeks) | 
| Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period | Anxiety Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline; End of Week 12 (12 Weeks) | 
| Hospital Anxiety Depression Scale: Depression Score at Baseline | Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline | 
| Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period. | Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline; End of Week 6 (6 weeks) | 
| Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period | Depression Scale - 7 items scored for each individual question from 0 = best and 3 = worst. HADS is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A negative value indicates that there has been an improvement. | Baseline; End of Week 12 (12 Weeks) | 
| Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period. | Tapentadol hydrochloride PR dose after 5 weeks of titration which was to be kept stable during the remained of the trial. | Week 6 | 
| Participant's Satisfaction With Previous Analgesic Treatment at Baseline | Participants were requested to rate their previous analgesic medication on a 5-point scale. Previous analgesic medication was rated as excellent, very good, good, fair and poor. | Baseline | 
| Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period. | Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor. | End of Week 6 | 
| Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period. | Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor. | End of Week 8 | 
| Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period. | Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor. | End of Week 12 | 
| Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | Baseline | 
| NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | End of Week 6 | 
| NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | End of Week 12 | 
| Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | Baseline | 
| NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | End of Week 6 | 
| NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period. | For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated no pain and a score of 10 indicated pain as bad as you can imagine. | End of Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low back pain, pain, assessment, tapentadol, centrally acting analgesic