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

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.