A Double-blind, Placebo-controlled, Randomized Dose Ranging Trial to Determine the Safety and Efficacy of Three Dose Levels of EMA401 in Reducing 24-hour Average Pain Intensity Score in Patients With Post-herpetic Neuralgia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Dose-response in Change in Weekly Mean of the 24-hour Average Pain Score, Using an 11-point Numeric Rating Scale (NRS), From Baseline to Week 12
研究概览
简要总结
This study was designed to characterize dose response, and evaluate safety and efficacy of three different doses of EMA401 compared to placebo in patients with post-herpetic neuralgia (PHN).
详细描述
This was an interventional, randomized, parallel, placebo-controlled, dose ranging, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. The study was planned in two cohorts. The initial cohort had three treatment arms i.e. Placebo b.i.d., EMA401 25 mg b.i.d., or EMA401 100 mg b.i.d. Following an unblinded safety review by an independent DMC, the second cohort was to have been initiated with an additional treatment arm i.e. EMA401 300 mg b.i.d.. Due to the premature study termination, the second cohort was not initiated. At the end of treatment period the 25mg BID and 100mg BID arms were 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
- 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
- •At the time of Screening, must have had documented diagnosis of PHN (ICD-10 code B02.29), defined as pain in the region of the rash persisting for more than 6 months after onset of herpes zoster rash.
- •Assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS ≥ 4).
- •Patients must have had documented past and/or ongoing inadequate treatment response (having insufficient pain relief with treatment or inability to tolerate) to at least 2 different prescribed therapies commonly used to treat and considered effective by the Investigator for the treatment of PHN.
- •Patient must have been willing to complete daily eDiary
排除标准
- •History or had current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study
- •Had a 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
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
- •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.
- •Patients who had a known diagnosis of diabetes and are stable on medication with a hemoglobin A1c > 8%. Those who did not have a known diagnosis of diabetes with a hemoglobin A1c > 7%.
研究组 & 干预措施
EMA401 100mg BID
Ema401 100 mg was administered orally twice a day
干预措施: EMA401 (Drug)
EMA401 25mg BID
Ema401 25 mg was administered orally twice a day
干预措施: EMA401 (Drug)
Placebo BID
Matching placebo capsules administered orally twice a day
干预措施: Placebo (Drug)
结局指标
主要结局
Dose-response in Change in Weekly Mean of the 24-hour Average Pain Score, Using an 11-point Numeric Rating Scale (NRS), From Baseline to Week 12
时间窗: Baseline up to Week 12
Since the 300 mg b.i.d. dose of EMA401 could not be initiated in the study due to premature study termination, the dose-response characterization was not performed. Specifically, only the trend test deduced from the set of candidate models was performed but the dose response estimation was not conducted.
次要结局
- 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)
- Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale(Baseline up to Week 12)
- Change in Neuropathic Pain Symptom Inventory (NPSI) 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)
- Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12(Week 8, Week 12)
- Exposure-response (Decrease in Pain Intensity) Via Evaluation of Effect of EMA401 Exposure on Efficacy Variables (e.g. Change From Baseline of Pain Score), Via Descriptive Pharmacokinetics/ Pharmacodynamics (PK/PD)(Baseline, Week 8, Week 12)
- Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) 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)
- Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale(Baseline up to Week 12)
- Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up(Approximately from 3 weeks after end of study up to 16 weeks)