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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要疼痛性糖尿病周围神经病变 (pDPN) 是一种严重且使人衰弱的神经功能障碍，常见于糖尿病患者。它导致下肢感觉疼痛，对 3000 万美国糖尿病患者产生不利影响，肌肉无力、容易跌倒、生活质量下降以及患者的显着发病率据估计，足部溃疡、截肢和残疾每年造成 109 亿美元的损失。仅在美国，大部分费用归因于足部溃疡和叠加感染的治疗。尽管 pDPN 对患者和患者产生了重大的经济和医疗影响，但治疗仍然有限。美国医疗保健系统提倡使用针对症状的治疗指南。 pDPN，可能包括使用抗惊厥药、抗抑郁药和阿片类药物作为一线治疗。然而，这些疗法只能提供适度的疼痛缓解，其不良事件超过了 FDA 的疼痛减轻。过去两年几乎没有批准任何新类别的镇痛药用于治疗神经性疼痛几十年来，在开发有效且安全的 pDPN 特异性替代疗法方面造成了巨大的漏洞。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型水溶性大麻二酚-棕榈酰乙醇酰胺 (CBD-PEA) 技术避免了这种情况。首过代谢并介导多种疼痛途径，提供最佳的抗炎和缓解作用我们的 CBD-PEA 药物可以消除当前疗法的副作用，因此，允许所有或几乎所有 pDPN 患者而不是仅 50% 的患者感受到疼痛缓解。 Pure Green Pharmaceuticals（公司）在已发表的临床数据中显示出初步成功证明含 CBD 的低剂量水溶性舌下片剂的舌下给药（60 毫克/天）和 PEA（300 毫克/天），对于慢性糖尿病神经病变患者，显着减轻疼痛，改善睡眠质量，减少焦虑 [开放标签试验中 p< 0.0001，N=31]。在一项验证性双盲、安慰剂对照试验中 [p<0.0001，N=54] 没有报告不良事件。拟议的项目大大扩展了公司最近发布的两份报告中所展示的能力基础性 2 期临床试验，有力地证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水溶性 20 毫克 CBD 和微粉化药物的影响和功效 100 毫克 PEA 舌下含片用于患有 pDPN 的患者这种直接进入 II 期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 方面的功效的临床试验与安慰剂对照相比，患者的焦虑和睡眠质量有所降低，这项为期 12 周的随机试验，双盲、安慰剂对照分散试验将在美国招募 200 名患者。