A Double-blind, Placebo-controlled, Randomized Trial to Determine the Safety and Efficacy of EMA401 in Reducing 24-hour Average Pain Intensity Score in Patients With Painful Diabetic Neuropathy (EMPADINE)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
研究概览
简要总结
The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in patients with painful diabetic neuropathy (PDN).
详细描述
This was an interventional, randomized, parallel, placebo-controlled, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. Patients were planned to be randomized in a 1:1 ratio to Placebo b.i.d. or EMA401 100 mg b.i.d.. Concomitant use of pregabalin or duloxetine at stable doses was allowed. Based on historical data, it was planned that the study would enroll approximately 50% of patients who were on stable doses of concomitant pregabalin or duloxetine in the study. At the end of treatment period the 100mg b.i.d. arm was re-randomized (1:1) to the same treatment or placebo. Placebo arm stayed on placebo. The planned duration of treatment period was 12 weeks and 1 week of treatment withdrawal at the end of treatment period.
The study was terminated early due to pre-clinical toxicity data that became available after start of trial. Novartis implemented a Urgent Safety Measure (USM) which instructed sites to discontinue study treatment immediately and to have all patients return for additional laboratory assessments (full hematology including coagulation and clinical chemistry panel). Safety data from the USM was presented as a separate outcome measure table and not included in the Adverse Event section
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
- Triple (Participant, Care Provider, Investigator)
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
- •At the time of Screening, must have had documented diagnosis of Type I OR Type II diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy (ICD-10 code G63.2) of more than 6 months duration with any one or more of the following:
- •Neuropathic symptoms (e.g. numbness, non-painful paresthesias or tingling, non-painful sensory distortions or misinterpretations, etc.)
- •Decreased distal sensation (e.g. decreased vibration, pinprick sensation, light touch, etc.)
- •Been assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS ≥ 4).
- •A score of ≥4 on the Douleur Neuropathique en 4 Questions (DN4) questionnaire at Screening.
排除标准
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 3 days after stopping of study medication. Highly effective contraception methods included:
- •Total abstinence (when this was is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception.
- •Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment.
- •Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should have been the sole partner for that subject.
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- •History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study.
- •Major depressive episode within 6 months prior to Screening and/or a history of diagnosed recurrent major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria.
- •Had evidence of significant renal insufficiency or pre-existing liver condition.
- •Had platelets ≤ 100 x 10^9/L, or neutrophil count < 1.2 x 10^9/L (or equivalent), hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men.
- •Participants whose glycemic control had been unstable within 3 months immediately prior to screening (e.g., ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention, uncontrolled hyperglycemia)
- •Patients who had any differential diagnosis of PDN including but not limited to other neuropathies (e.g. Vitamin B12 deficiency, Chronic Inflammatory Demyelinating Polyneuropathy), polyradiculopathies, central disorders (e.g. demyelinating disease), or rheumatological disease (e.g., foot arthritis, plantar fasciitis).
- •Patient was unwilling or unable to complete daily eDiary.
研究组 & 干预措施
EMA401
During the treatment epoch, patients will receive EMA401 for 12 weeks. During the treatment withdrawal epoch, patients will receive EMA401 or matching placebo for 1 week.
干预措施: EMA401 (Drug)
EMA401
During the treatment epoch, patients will receive EMA401 for 12 weeks. During the treatment withdrawal epoch, patients will receive EMA401 or matching placebo for 1 week.
干预措施: Placebo (Drug)
Placebo
Participants will receive matching placebo to EMA401 during both the treatment and treatment withdrawal epochs for a total of 13 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
时间窗: Baseline up to Week 12
The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.
次要结局
- Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12(Baseline up to Week 12)
- Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12(Baseline up to Week 12)
- Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12(Baseline up to Week 12)
- Number of Participants Per Patient Global Impression of Change Category at Week 12(Baseline up to Week 12)
- Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12(Baseline up to Week 12)
- Time to First Rescue Medication Intake(Baseline up to day 92)
- Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up(Approximately from 3 weeks after end of study up to 16 weeks)
- Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale(Baseline up to Week 12)
- Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale(Baseline up to Week 12)
- Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12(Week 8 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours))
- Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period(Baseline and weekly up to 12 weeks, once during double-blind period)
- Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period(Week 12 to Week 13 (planned duration subject to varibility in visit scheduling))