Evaluation of the Effectiveness, Safety, and Tolerability of Tapentadol PR Versus Oxycodone/Naloxone PR in Non-opioid Pre-treated Subjects With Uncontrolled Severe Chronic Low Back Pain With a Neuropathic Pain Component.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 367
- 试验地点
- 50
- 主要终点
- Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Tapentadol Prolonged Release (PR)
干预措施: Tapentadol Prolonged Release (Drug)
Oxycodone/Naloxone Prolonged Release
干预措施: Oxycodone/Naloxone Prolonged Release (Drug)
结局指标
主要结局
Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3)
时间窗: 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
时间窗: 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).
次要结局
- Recalled Average Pain Intensity(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in Recalled Average Pain Intensity at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- 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))
- Worst Pain Intensity Over the Past 24 Hours(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- painDETECT Final Assessment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in painDETECT Final Assessment at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Hospital Anxiety and Depression Scale: Anxiety(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- 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))
- Short Form Health Survey (SF-12)(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Changes in the Short Form Health Survey (SF-12) at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- EuroQol-5 (EQ-5D) Health Status Index Outcome(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Hospital Anxiety and Depression Scale: Depression(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Patient Global Impression of Change at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Clinician Global Impression of Change at the End of Treatment(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation: Number of Awakenings(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation: Number of Hours Slept(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- Sleep Evaluation: Latency (Time Taken to Fall Asleep)(Baseline (Randomization Visit); End of Continuation Period (Week 12))
- 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))
- 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))
- 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))