Combination Therapeutic for Chronic Opioid Use Disorder Relapse

慢性阿片类药物使用障碍复发的联合治疗

基本信息

批准号：
10706844
负责人：
TREVOR P. CASTOR
金额：
$ 33.57万
依托单位：
APHIOS CORPORATION
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：
2023-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10706844
关键词：
Acids Address Adherence Adult Adverse effects Aftercare Alcohol consumption Alcohol dependence Alcohols Animal Model Animals Arousal Behavior Binding Biological Availability Buprenorphine Cannabidiol Cannabinoids Cannabis sativa plant Chronic Clinical Clinical Trials Conduct Clinical Trials Cue-induced relapse Cues Cyclic GMP Dependence Development Dose Drug Combinations Economic Burden Economics Encapsulated Epidemic FDA approved Female Formulation Frequencies Friends Funding Future Health Care Costs Hemp Heroin Human Hydrophobicity In Vitro Individual Industry Insulin Intramuscular Legal patent Licensing Marijuana Medical Methadone Morphine Motivation Mus Naltrexone Nanosphere Narcotics Opiate Addiction Opioid Opioid Antagonist Opioid abuser Opioid agonist Patients Personal Satisfaction Persons Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Phase Polymers Prevention Proteins Public Health Regulatory Pathway Relapse Reporting Research Risk Safety Sister Stomach Stress Technology Therapeutic Treatment Efficacy United States Wistar Rats Withdrawal Withdrawal Symptom addiction age group biodegradable polymer bryostatin clinical development craving delta opioid receptor experience improved in vivo in vivo evaluation lofexidine male manufacture manufacturing scale-up mu opioid receptors nano nanoencapsulated nanoformulation nanoparticle nanopolymer non-compliance non-opioid analgesic novel opioid epidemic opioid overdose opioid use opioid use disorder opioid withdrawal pain symptom pandemic disease programs relapse prevention research and development response scale up side effect social success treatment adherence treatment duration uptake

项目摘要

PROJECT SUMMARY Few therapeutics are available for individuals trying to recover from opioid use disorder. Buprenorphine and methadone, opioid receptor agonists, are approved by the FDA to treat Opioid Use Disorder (OUD) but long- term efficacy and treatment adherence are sub-optimal. Extended-release naltrexone (Vivitrol®, Alkermes), a full µ-opioid receptor antagonist, was approved by the FDA in 2010 for the prevention of relapse to opioid dependence but initiation and adherence to treatment are low. There is an urgent need for improved treatments for chronic relapsing opioid use disorder that has serious public health consequences. For the treatment of chronic relapsing OUD, we propose to develop an extended-release combination of low- dose naltrexone and cannabidiol (CBD) by nanoencapsulating them in biodegradable polymer nanospheres using an environmental-friendly proprietary SuperFluids™ technology. CBD has been shown to inhibit cue- induced heroin seeking in animals, and subsequent human clinical trial studies have revealed its potential utility and safety. Animal studies have shown that low-dose naltrexone, when combined with CBD, is better than either of the two in isolation to improve motivation and alcohol consumption in mice. This combination is promising, considering that naltrexone primarily targets the μ opioid receptor, and CBD binds the μ and δ opioid receptors. Lowering the dose of naltrexone will be impactful since it will reduce the side effects of Vivitrol®, and improve safety and compliance. This novel formulation will significantly enhance the bioavailability and pharmacodynamics of the two therapeutics, reduce dose frequency, and improve addiction treatment adherence. In Phase I, we will develop nanoformulations of CBD and low-dose naltrexone/CBD in biodegradable polymer nanospheres, and assess the intramuscular administration of the nanoparticles to reduce OUD relapse compared to Vivitrol® in an animal model of OUD relapse. In Phase II, we will conduct a more extensive R&D program that includes scale-up of cGMP manufacturing, GLP in vitro and in vivo product characterization, and establish the regulatory pathway for clinical development. In Phase III, with strategic corporate partners and/or investors, we will conduct clinical trials of CBD/naltrexone PLGA nanoparticles in patients suffering from chronic relapsing opioid use disorder.

项目概要对于试图从丁丙诺啡和丁丙诺啡使用障碍中恢复的个体来说，可用的治疗方法很少。美沙酮是阿片受体激动剂，经 FDA 批准用于治疗阿片类药物使用障碍 (OUD)，但长期缓释纳曲酮（Vivitrol®，Alkermes）的长期疗效和治疗依从性不佳。完全μ阿片受体拮抗剂，于2010年被FDA批准用于预防阿片类药物复发依赖性，但治疗的起始和依从性较低迫切需要改进的治疗方法。用于治疗具有严重公共卫生后果的慢性复发性阿片类药物使用障碍。为了治疗慢性复发性 OUD，我们建议开发一种低浓度的缓释组合。通过将纳曲酮和大麻二酚（CBD）纳米封装在可生物降解的聚合物纳米球中来剂量使用环保的专有 SuperFluids™ 技术已被证明可以抑制提示。诱导动物寻找海洛因，随后的人体临床试验研究揭示了其潜在用途动物研究表明，低剂量纳曲酮与 CBD 结合使用比任何一种都更好。单独使用这两种方法来提高小鼠的动力和饮酒量，这种组合是有前途的，考虑到纳曲酮主要针对μ阿片受体，而CBD结合μ和δ阿片受体。降低纳曲酮的剂量将会产生影响，因为它会减少 Vivitrol® 的副作用，并改善这种新颖的配方将显着提高生物利用度和依从性。两种疗法的药效学，减少剂量频率，并提高成瘾治疗的依从性。在第一阶段，我们将开发可生物降解聚合物中的 CBD 和低剂量纳曲酮/CBD 纳米制剂纳米球，并评估纳米颗粒的肌肉注射以减少 OUD 复发与 OUD 复发动物模型中的 Vivitrol® 相比，我们将进行更广泛的研发。计划，包括 cGMP 生产规模扩大、GLP 体外和体内产品表征，以及与战略企业合作伙伴和/或建立第三阶段临床开发的监管途径。投资者，我们将在慢性病患者中进行 CBD/纳曲酮 PLGA 纳米颗粒的临床试验复发性阿片类药物使用障碍。