Evaluation of the Efficacy, Tolerability, and Safety of 7 Days of Treatment With GRT6010 or Pregabalin in Comparison to Placebo in Subjects With Peripheral Neuropathic Pain.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 114
- 试验地点
- 12
- 主要终点
- Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores
研究概览
简要总结
The purpose of this trial is to determine whether a novel analgesic is effective in treating of neuropathic pain caused by herpetic infection, surgery, or trauma.
详细描述
This trial evaluates the effectiveness of a novel analgesic in peripheral neuropathic pain in a mixed patient population. Participants were treated for one week and randomly assigned to the novel analgesic, pregabalin, or placebo. Pain will be characterized before and at the end of this period. This trial required the participants to stay at the investigational site for 14 consecutive days.
The enrollment visit took place Day -28 to Day -16. Participants tapered down their existing medication from Visit 2 (Day -17 to Day -5) to Visit 3 and were given rescue medication (paracetamol/acetaminophen). At Visit 3 participants were hospitalized (Day -4). The baseline evaluation period took place from Day -3 to Day -1. Randomization to one of the three treatment arms was possible after the last assessment on Day - 1 alternatively randomization took place on Day 1. This was followed by the double-blind treatment period (Day 1 to Day 7). The participants were follow-up thereafter up to day 36 (Day 34 to 38). Participants were permitted to resume their previous medication.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years to 75 years
- •Presence of persistent neuropathic pain for at least 6 months at the time of the Enrollment Visit. Allowed reasons for neuropathic pain are: modified radical mastectomy, breast conserving surgery, or cosmetic breast surgery. [Germany: subjects after cosmetic breast surgery may not be enrolled.]
- •Presence of "probable" or "definite" neuropathic pain.
- •Presence of dynamic mechanical allodynia on the affected side, or alternatively, the mechanical pain sensitivity for any of the pinprick stimuli is higher on the affected compared to the contralateral side.
- •At either Visit 5 or Visit 6: Presence of an average evoked pain intensity score of >20 on the 0 100 point numeric rating scale (NRS) for at least 1 of the 3 clinical sub-tests for dynamic mechanical allodynia (i.e., standardized brush, cotton wool tip or cotton wisp). The average will be calculated as the arithmetic mean of all measurements per sub test. Alternatively, the arithmetic mean of the 5 test replicates for any of the pinprick stimuli for mechanical pain sensitivity is at least 3 times higher for the affected side compared to the contralateral side.
- •Presence of an average ongoing pain intensity score of >4 to <9 on the 0-10 point numerical rating scale (NRS) without the use of rescue medication within the 3 day Baseline pain intensity evaluation Period with at least 7 of 9 assessments being present.
- •Dissatisfaction with the current treatment (i.e., lack of efficacy or intolerable side effects) if taking an opioid or non opioid analgesic medication for the painful neuropathy before enrollment.
排除标准
- •Any kind of hepatic impairment at Visit 1 or at Visit
- •Either active hepatitis within the past 3 months or presence of chronic hepatitis irrespective of its activity status.
- •Estimated creatinine clearance of less than 60 mL/minute x 1.73 m2 at either Visit 1 or at Visit
- •Clinically relevant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society [CCS] Grade III to IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association [NYHA] Class III to IV).
- •Electrocardiogram (ECG) with clinically relevant findings at either Visit 1 or at Visit 3, including but not limited to repeated prolongation of QTc > 450 ms (Fridericia correction), or a history of additional risk factors for torsade de pointes (e.g., family history of Long QT Syndrome).
- •Clinically relevant pulmonary disease (e.g., Medical Research Council breathlessness scale of 2 or above).
- •Specific antitumor therapy within the last 6 months, e.g., adjuvant radiotherapy or chemotherapy, biologics, or angiogenesis inhibitors.
- •CYP2D6 poor metabolizer phenotype as predicted by CYP2D6 genotyping.
- •Presence of confounding pain conditions (e.g., ulnar nerve entrapment, radial nerve injury associated with major soft-tissue or bone damage, cervico-thoracic radiculopathy, carpal tunnel syndrome, chemotherapy-induced peripheral neuropathy, or complex regional pain syndrome type I or type II).
- •Phantom breast or phantom limb pain.
- •Presence of exclusively negative symptoms of neuropathic pain (e.g., hypoesthesia or total anesthesia) in the affected area.
研究组 & 干预措施
GRT6010
Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
干预措施: GRT6010 (Drug)
Matching placebo
Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
干预措施: Matching Placebo (Drug)
Pregabalin
Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
干预措施: Pregabalin (Drug)
结局指标
主要结局
Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores
时间窗: Baseline; Day 7 (end of double blind treatment)
The baseline pain intensity score was calculated as a mean of pain intensity scores during the Baseline Period (from Day -3 to Day -1). The ongoing pain intensity data from Day-3 to Day 7 was used. For the analysis, only pain scores on days where participants received study drug were considered. The primary efficacy analysis of the ongoing pain intensity score were analyzed in a Bayesian framework, via a mono exponential decay model, with the baseline Numeric Rating Score (NRS) as intercept. Considering the inclusion criteria of baseline pain intensity being in the range from 4 to 9, the range in ongoing pain intensity difference between baseline and end-of-double-blind treatment can be from 6 (worst possible value) to -9 (best possible value). A negative value indicates improvement whilst on the treatment.
The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores
时间窗: Baseline and day 7 (end of double blind treatment)
The difference between baseline and end-of-double-blind treatment brush-evoked pain intensity scores compared to placebo on a 0-100 point NRS (measured as part of the dynamic mechanical allodynia assessments). Each participant rated each brush-evoked pain intensity on a 0 to 100 point Numerical Pain Rating Scale, with 0 indicating 'No Pain' and 100 indicating 'most intense pain imaginable'. Lower values compared to an individual subject's baseline are an improvement in symptoms. The baseline brush-evoked pain intensity score was defined as the average of the geometric mean of all of the values obtained on Day -2 and Day -1, and compared with the scores obtained on day 6 and 7. For the analysis, only pain scores on days where participants received study drug were considered. A negative change indicates a decrease in brush-evoked pain intensity from baseline.
次要结局
- Change in Area of Static Allodynia and Dynamic Allodynia From Baseline(Baseline; Day 7 (end of double blind treatment))
- Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7)(Day 7 (end of double blind treatment))
- Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1)(Day -1; Day 7 (end of double blind treatment))
- Onset of Current Pain Relief(Day 1 to Day 7 (end of double blind treatment))
- Onset of Ongoing Pain Relief(Day 1 to Day 7 (end of double blind treatment))
- Difference in Patient's Global Impression of Change(Day 7 (end of double blind treatment))
- The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo(Day 7 (end of double blind treatment))
- Assessment of Responder Rates(Day 7 (end of double blind treatment))
- Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment(Day 7)
- Daily Current Pain Intensity(Baseline; Day 10)