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

项目摘要/摘要 痛性糖尿病周围神经病变(PDPN)是一种严重的、使人衰弱的神经功能障碍，在 3000万美国糖尿病患者。它会对患者产生不利影响，因为它会导致下肢的感觉性疼痛， 肌肉无力，易摔倒，生活质量下降，以及显著的患者发病率 足部溃疡、截肢和残疾的结果。PDPN估计每年花费109亿美元在 仅在美国，大部分费用被归因于足部溃疡和重叠感染的治疗。 PDPN的治疗仍然有限，尽管对患者和 美国的医疗体系。既定的指南主张使用针对以下症状的治疗方法 PDPN，并可能包括作为一线治疗的抗惊厥药、抗抑郁药和阿片类药物的管理。 然而，这些疗法只能提供适度的疼痛缓解，不良反应超过了疼痛减轻。美国食品和药物管理局 在过去的两年里，几乎没有批准任何新的类别的止痛药来治疗神经性疼痛 几十年，在开发有效和安全的pDPN特定替代疗法方面造成了一个巨大的漏洞。 这个项目通过我们的临床演示介绍了pDPN治疗方面的重大创新。 新型水溶性大麻二醇棕榈酰乙醇胺(CBD-PEA)技术。该提法避免了 首次通过新陈代谢和调节多条疼痛通路，提供最佳的抗炎和 抗氧化剂的临床结果。我们的CBD-PEA药物可能会消除现有疗法的不良反应， 因此，允许所有或几乎所有pDPN患者体验疼痛缓解，而不是只有50%的患者。 Pure Green PharmPharmticals(本公司)已在已公布的临床数据中取得初步成功 低剂量含CBD水溶舌下含片的舌下给药 (60毫克/天)和PEA(300毫克/天)，对慢性糖尿病神经病变患者，显著减轻疼痛， 改善睡眠质量，减少焦虑[P&lt；0.0001在开放标签试验中，N=31]。类似的结果也出现了 在一项验证性双盲、安慰剂对照试验中[p&lt；0.0001，N=54]。没有不良反应的报道。 拟议的项目极大地扩展了公司在最近公布的两个项目中展示的能力 基础的第二阶段临床试验，强烈建议临床和统计证据的有效性和 PDPN中CBD-PEA的安全性。 这项研究将确定该公司的水溶性20 mg CBD和微粉化的影响和疗效 100 mg PEA舌下含片治疗pDPN这一直接到第二阶段是一个里程碑驱动的 通过测量疼痛来验证PG Pharma的独特配方在减少pDPN方面的疗效的临床试验 与安慰剂对照组相比，减少了患者的焦虑和睡眠质量。这项为期12周的随机试验， 双盲、安慰剂对照的分散试验将在全美招募200名患者。

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.