CTRI/2021/08/035410招募中2 期
A Phase 2b, randomized, double-blind, placebo controlled dose-finding study to evaluate efficacy, safety and tolerability of GRC 17536 in patients with painful diabetic peripheral neuropathy.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 472
- 试验地点
- 30
- 主要终点
- Change from baseline in mean 24-hour API score as measured by 11-point NRS
研究概览
简要总结
Diabetic peripheral neuropathy (DPN) represents a diffuse symmetric and length-dependent injury to peripheral nerves that has major implications on quality of life (QOL), morbidity, and costs from a public health perspective. Diabetic peripheral neuropathy (DPN) is a common complication of both Type 1 and 2 diabetes mellitus, which affects 30% to 90% of the diabetic patients. Pharmacological agents used in the management of painful DPN mainly include tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, opioid, and anti-epileptic drugs. In general, the available treatment options do not provide total relief, are not effective in all patients, and only about one-third of patients may achieve more than 50% pain relief. Hence newer therapies are required for the treatment of painful DPN. GRC 17536 is a novel small molecule targeting TRPA1 as an antagonist and is undergoing clinical development for treatment of painful DPN.
The proposed Phase 2b trial will assess dose-range effect of GRC 17536 for treatment of painful DPN and the study will be conducted across multiple centres in India.
The primary outcome measures will be the change from baseline to end of treatment in the mean 24-hour average pain intensity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Each subject must meet all of the following criteria to be randomized in the study:
- •Subject voluntary willing to provide written informed consent; and willing to comply with all aspects of the protocol.
- •Type 1 or Type 2 diabetes mellitus male and female (post-menopausal/surgically sterile females only) subjects with age between 18 and 75 years (inclusive of both) at the time of informed consent.
- •A history of pain for at least 6 months and no greater than 5 years attributed to DPN.
- •Subjects with cold detection and warm detection present.
- •Douleur Neuropathique en 4 questions (DN4) score ≥
- •Moderate to severe pain due to DPN.
- •Treatment naïve subjects or subjects on treatment with DPN pain medication with pain not adequately controlled with the medication.
- •HbA1c (glycosylated hemoglobin) level ≤8%.
- •Must be willing to use appropriate contraceptive precautions as defined in the study protocol.
排除标准
- •A subject who meets any of the following criteria must not be entered into the run-in phase/randomized in the study:
- •Other chronic pain conditions not associated with DPN that may confound the assessment of pain in DPN.
- •Use of a capsaicin patch within 6 months prior to Screening.
- •Subjects who are currently taking opioids for their painful DPN.
- •Recent hospitalization due to hypo or hyperglycemia within the last 3 months prior to the Screening Visit.
- •Complex regional pain syndrome or trigeminal neuralgia.
- •Active diabetic foot ulcer.
- •Subject has any of the following laboratory abnormalities, medical conditions, or disorders: a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥1.5x upper limit of normal (ULN) or total bilirubin ≥1.2x ULN.
- •b) Folate or Vitamin B12 levels < lower limit of normal (LLN).
- •c) Chronic hepatitis B or C with a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Core Antigen Antibody (Hep C antibody).
- •d) Blood urea nitrogen ≥1.5x the ULN.
- •e) Creatinine clearance (CrCL) ≤60 mL/min as determined by the central laboratory using the modified Cockcroft-Gault equation.
- •j) SARS-CoV2 infection within 4 weeks before Screening and any persisting post-infection symptoms at the time of Screening.
- •Current diagnosis of major depression or taking medications for it.
- •Subjects who have undergone gastrointestinal surgery that could affect the absorption of investigational product (e.g., bariatric surgery).
- •Subjects with a history of human immunodeficiency virus (HIV) infection.
- •Subject is positive for urine opioid/cannabinoid tests.
- •Participants answering "Yes" to any of the questions about active suicidal ideation/intent/behaviors occurred within the past month.
结局指标
主要结局
Change from baseline in mean 24-hour API score as measured by 11-point NRS
时间窗: Week 12
次要结局
- Change from baseline in mean 24-hour API score(Week 3, 6, 9, and 16)
- Proportion of subjects achieving 30% reduction in the mean 24-hour API score(Week 3, 6, 9, 12, and 16)
- Proportion of subjects achieving 50% reduction in the mean 24-hour API score(Week 3, 6, 9, 12, and 16)
- Time to onset of sustained improvement in the 24-hour API score(Day of onset of sustained improvement)
- Change in mean worst pain intensity (WPI) in last 24 hours [Time points(Week 3, 6, 9, 12, and 16)
- Change in mean night-time API score(Week 3, 6, 9, 12, and 16)
- Change in mean night-time WPI score(Week 3, 6, 9, 12, and 16)
- Change in mean sleep interference score(Week 3, 6, 9, 12, and 16)
- Proportion of subjects who are responders on the Patient Global Impression of Change questionnaire(Week 6, 12, and 16)
- Change in Neuropathic Pain Symptom Inventory (NPSI) score(Week 6 and 12)
- Change in quality of life parameters as per SF-12 score(Week 6 and 12)
- Cmax, Tmax, AUC, AUC0-tau, and AUC0-24 for GRC 17536.(PK sampling time points: Day 3, 4, 7, 9, 15, 18, 25 and Day 29)
- Adverse events by type, severity, causality and seriousness(From Study initiation to end of study)
- Columbia-Suicide Severity Rating Scale (C-SSRS)(From baseline to Week 12)
研究者
研究点 (30)
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