A Randomized-Withdrawal, Placebo-Controlled, Study Evaluating the Efficacy, Safety, and Tolerability of Tapentadol Extended-Release (ER) in Subjects With Chronic, Painful Diabetic Peripheral Neuropathy (DPN)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 460
- 主要终点
- Change From Double-Blind Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and tolerability of orally administered tapentadol extended release (ER) at dosages of 100 to 250 mg twice daily compared with placebo in patients with moderate to severe pain due to chronic, painful diabetic peripheral neuropathy (DPN) who tolerated tapentadol (ER) and have an initial treatment effect (pain improvement) after a 3-week, open-label titration period.
详细描述
This is a randomized-withdrawal (only patients that have an initial response to tapentadol are assigned to either tapentadol or placebo), placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of orally administered tapentadol, using the extended release tamper-resistant formulation (TRF), at dosages of 100 to 250 mg twice daily in patients with moderate to severe pain due to chronic, painful DPN. The study consists of 1) an open-label (all people involved know the identity of the intervention) phase, including a 13-day screening period, a 5-day washout period (where patients are to stop taking their pain medication), a 3-day pre-titration pain-intensity evaluation period (where patients will record their pain intensity twice daily in the morning and evening), and a 3-week, open-label titration period (all patients receive tapentadol study drug), 2) a 12-week, double-blind (neither physician nor patient knows the name of the assigned drug) maintenance phase, and 3) a posttreatment phase of approximately 10 to 14 days. The study will evaluate the effectiveness of orally administered tapentadol ER versus placebo in reducing patients' pain intensity. The pain intensity will be assessed by comparing the baseline pain level to the level at week 12 of the maintenance phase. The total duration of study drug treatment for each patient will be approximately 15 weeks. Safety and tolerability will be evaluated by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms (ECGs), standardized neurologic examinations, and monitoring of adverse events. Patients will be titrated on tapentadol ER from a starting dose of 50 mg twice daily to the patient's optimal dose ranging between 100 mg and 250 mg twice a day, or placebo. All doses of study medication will be taken orally with approximately 120 ml of water with or without food for a maximum timeframe of 15 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients with Type 1 or 2 diabetes mellitus must have a documented clinical diagnosis of painful diabetic peripheral neuropathy with symptoms and signs for at least 6 months, and pain present at the time of screening
- •Diagnosis must include pain plus reduction or absence of pin sensibility and/or vibration sensibility on Total Neuropathy Score - Nurse (TNSn) examination in lower and/or upper extremities at screening
- •The investigator considers the patient's blood glucose to be controlled by diet, or hypoglycemics, or insulin for at least 3 months prior to enrolling in the study
- •Patients have been taking analgesic medications for the condition for at least 3 months prior to screening (patients taking opioid analgesics must be dissatisfied with current treatment, and patients taking non-opioid analgesics must be dissatisfied with current analgesia)
- •Patients currently requiring opioid treatment must be taking daily doses of an opioid-based analgesic equivalent to <=160mg of oral morphine
排除标准
- •Significant history of pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately as in schizophrenia)
- •History of moderate to severe hepatic impairment
- •Severely impaired renal function
- •Clinically significant laboratory abnormalities
- •Clinically significant cardiac disease
- •History of seizure disorder or epilepsy
- •History of any other clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise patient safety during study participation
研究组 & 干预措施
Tapentadol Extended Release (ER)
干预措施: Tapentadol extended release (ER) (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Double-Blind Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12
时间窗: Double-Blind Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period)
For this twice daily pain assessment, the patients were to indicate the level of pain experienced over the previous 12 hours 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".
次要结局
- Responder Analysis: Proportion of Patients With At Least 50% Improvement From Baseline of Open-Label on the Numerical Rating Scale (NRS) at the Week 12 Endpoint(Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind))
- Distribution of Patient Global Impression of Change at Week 12 Endpoint(End of Double-Blind Treatment at 12 Weeks)
- Change From Baseline of Open-Label in the Pain Intensity Subscale of the Brief Pain Inventory (BPI) at the Week 12 Double-Blind Endpoint(Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind))
- Change From Baseline in the EuroQoL-5 Dimension (EQ-5D) Health Status Index at the Week 12 Endpoint(Double-blind Baseline and End of Double-Blind Treatment at 12 Weeks)