Cannabidiol/Palmitoylethanolamide sublingual tablets for the treatment of Painful Diabetic Peripheral Neuropathy

大麻二酚/棕榈酰乙醇酰胺舌下片用于治疗疼痛性糖尿病周围神经病变

• 批准号: 10761403
• 负责人: Salahadin Abdi
• 金额: $ 111.87万
• 依托单位: PURE GREEN PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761403
• 关键词: Adverse effects; Adverse event; Adverse reactions; Advocate; Affect; Alternative Therapies; Amputation; Analgesics; Anti-Inflammatory Agents; Anticonvulsants; Antidepressive Agents; Antioxidants; Anxiety; Biological Availability; Bypass; California; Cannabidiol; Case Report Form; Categories; Chronic; Clinical; Clinical Data; Clinical Protocols; Clinical Research; Clinical Trials; Collaborations; Combined Modality Therapy; Complex; Control Groups; Data; Decentralization; Development; Diabetic Neuropathies; Dimensions; Dose; Double-Blind Method; Economics; Electromyography; Endocannabinoids; Enrollment; Esthesia; Feedback; Foot Ulcer; Formulation; Friends; Functional disorder; Goals; Grant; Guidelines; Healthcare Systems; Individual; Infection; Institutional Review Boards; Investigation; Investigational New Drug Application; Measurement; Measures; Mediating; Medical; Metabolism; Morbidity - disease rate; Movement; Muscle Weakness; Nerve; Neural Conduction; Opioid; Outcome; Pain; Pain in lower limb; Pathway interactions; Patients; Peripheral Nerves; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Placebo Control; Predisposition; Prevention; Process; Program Development; Publishing; Quality of life; Questionnaires; Randomized; Regimen; Reporting; Research; Safety; Scientist; Sensory; Sleep; Small Business Innovation Research Grant; Sublingual drug administration; TRPV1 gene; Tablets; Technology; Testing; Therapeutic; Therapeutic Effect; United States; United States Food and Drug Administration; Universities; Water; Work; absorption; addiction liability; anxiety reduction; beta-Cyclodextrins; clinical development; cost; diabetic; diabetic patient; disability; double-blind placebo controlled trial; efficacy evaluation; efficacy validation; experience; falls; gamma-Aminobutyric Acid; improved; improvement on sleep; innovation; liver metabolism; multimodality; novel; novel therapeutics; open label; operation; pain reduction; pain relief; pain symptom; painful neuropathy; palmidrol; patient population; patient subsets; receptor; reduce symptoms; sleep quality; standard of care; statistics; success; tablet formulation; targeted treatment; uptake; virtual

PROJECT SUMMARY/ABSTRACT Painful diabetic peripheral neuropathy (pDPN) is a severe and debilitating nerve dysfunction prevalent in over 30 million US diabetic patients. It adversely affects patients by causing sensory pain in the lower limbs, muscular weakness, predisposition to falls, decreased quality of life, and significant patient morbidity as a result of foot ulcerations, amputations, and disability. pDPN is estimated to cost $10.9 billion per year in the US alone, with most costs attributed to the treatment of foot ulcers and superimposed infections. Treatment for pDPN remains limited despite the significant economic and medical impact on patients and the U.S. healthcare system. Established guidelines advocate the use of therapies targeting the symptoms of pDPN, and may include administration of anticonvulsants, antidepressants, and opioids, as first-line therapies. Yet, these therapies only offer moderate pain relief, with adverse events outweighing pain reduction. The FDA has approved virtually no new categories of analgesics for the treatment of neuropathic pain over the last two decades, creating a gaping hole in the development of effective and safe pDPN-specific alternative therapies. This project introduces a significant innovation in the treatment of pDPN through our clinically-demonstrated novel water-solubilized Cannabidiol-Palmitoylethanolamide (CBD-PEA) technology. The formulation avoids first-pass metabolism and mediates multiple pain pathways to provide the best anti-inflammatory and antioxidant clinical outcomes. Our CBD-PEA drug may eliminate the adverse effects of current therapies, therefore allowing all or nearly all pDPN patients to experience pain relief instead of only 50% of the patients. Pure Green Pharmaceuticals (The Company) has shown preliminary success in published clinical data demonstrating that sublingual administration of low-dose, water-solubilized sublingual tablets containing CBD (60 mg/day) and PEA (300 mg/day), to patients with chronic diabetic neuropathy, significantly reduced pain, improved sleep quality, and reduced anxiety [p< 0.0001 in an open-label trial, N=31]. Similar results were seen in a confirmatory double-blind, placebo-controlled trial [p<0.0001, N=54]. No adverse events were reported. The proposed project substantially expands the Company’s capabilities demonstrated in two recently published foundational Phase 2 clinical trials that strongly suggested clinical and statistical evidence for the efficacy and safety of CBD-PEA in pDPN. This study will determine the impact and efficacy of the Company’s water-soluble 20 mg CBD and micronized 100 mg PEA sublingual tablet in patients suffering from pDPN. This Direct-to-Phase II is a milestone-driven clinical trial to validate the efficacy of PG Pharma’s unique formulation in pDPN reduction, by measuring pain reduction, patients’ anxiety and sleep quality compared to placebo control. This 12-week randomized, double-blind, placebo-controlled decentralized trial will enroll 200 patients across the United States.

项目摘要/摘要 疼痛性糖尿病周围神经病变（pDPN）是一种严重的和衰弱的神经功能障碍， 3000万美国糖尿病患者它通过引起下肢感觉疼痛对患者产生不利影响， 肌无力、易患福尔斯、生活质量下降和显著的患者发病率， 导致足部溃疡、截肢和残疾。pDPN估计每年花费109亿美元， 仅美国，大部分费用归因于足部溃疡和叠加感染的治疗。 pDPN的治疗仍然有限，尽管对患者有显著的经济和医学影响， 美国的医疗保健系统。既定的指南提倡使用针对以下症状的治疗： pDPN，并可能包括抗惊厥药、抗抑郁药和阿片类药物的给药，作为一线治疗。 然而，这些疗法仅提供中度疼痛缓解，不良事件超过疼痛减轻。FDA的 在过去的两年里，几乎没有批准任何新的镇痛药类别用于治疗神经性疼痛。 几十年来，在有效和安全的pDPN特异性替代疗法的开发中创造了一个巨大的漏洞。 该项目通过我们的临床证明，在pDPN治疗方面引入了重大创新 新的水溶性大麻二酚-棕榈酰乙醇胺（CBD-PEA）技术。该配方避免了 首过代谢并介导多个疼痛途径，以提供最佳的抗炎和 抗氧化剂临床结果。我们的CBD-PEA药物可以消除目前治疗的不良反应， 因此允许所有或几乎所有的pDPN患者而不是仅50%的患者经历疼痛缓解。 Pure绿色制药（本公司）已在已发表的临床数据中显示出初步成功 证明舌下给药低剂量的含有CBD的水溶性舌下片剂 (60 mg/天）和PEA（300 mg/天）对慢性糖尿病性神经病变患者，显著减轻疼痛， 改善睡眠质量，减少焦虑[开放标签试验中p< 0.0001，N=31]。观察到相似结果 在一项验证性双盲、安慰剂对照试验中[p<0.0001，N=54]。未报告不良事件。 拟议的项目大大扩展了公司在最近公布的两份报告中展示的能力。 基础性2期临床试验，有力地表明了疗效的临床和统计证据， CBD-PEA在pDPN中的安全性。 这项研究将确定该公司的水溶性20毫克CBD和微粉化的影响和功效 在患有pDPN的患者中使用100 mg PEA舌下片剂。此直接到阶段II是一个里程碑驱动的 通过测量疼痛来验证PG Pharma独特配方在减少pDPN方面的疗效的临床试验 与安慰剂对照组相比，患者的焦虑和睡眠质量降低。这个为期12周的随机， 一项双盲、安慰剂对照的分散试验将在美国招募200名患者。