Developing a Novel Mixed Opioid Agonist for the Treatment of OUD

开发用于治疗 OUD 的新型混合阿片受体激动剂

• 批准号: 10338895
• 负责人: Ebrahim Versi
• 金额: $ 5.5万
• 依托单位: DMK PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-24 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10338895
• 关键词: Abstinence; Adherence; Agonist; American; Animal Experiments; Buprenorphine; Cessation of life; Clinical; Dose; Endorphins; Face; Health Professional; Individual; Intention; Life; Mediation; Medical Staff; Methadone; Morphine; Morphine Dependence; Opioid; Opioid agonist; Pain; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Physiological; Relapse; Rodent Model; Safety; Shame; Stress; System; Treatment Protocols; Ventilatory Depression; Withdrawal; Withdrawal Symptom; Work; active comparator; clinical development; craving; effective therapy; experience; improved; kappa opioid receptors; medication-assisted treatment; novel; opioid abuse; opioid agonist therapy; opioid use disorder; opioid withdrawal; small molecule; social stigma; standard of care

Project Summary Over 2.1 million Americans suffer from opioid use disorder (OUD) resulting in 47,000 deaths annually. Individuals seeking treatment must deal with stigma, limited access to qualified healthcare professionals and bureaucratic barriers to getting medication assisted treatment (MAT) and in addition often need to experience withdrawal symptoms prior to MAT which all add up to an ineffective system of access. Even on treatment, patients face several obstacles such as pain, craving, stress, shame, treatment inconsistency and relapse to be remain on an effective treatment regimen. This is just one of many steps needed towards long term abstinence and a more stable life. The path is harrowing, and there is a paucity of options available for these individuals and the medical staff who treat them. DMK proposes to expand MAT capabilities for OUD with DPI-125, with a small molecule, triple (mu, delta and kappa) opioid receptor agonist. Experimental, clinical and theoretical evidence suggests that DPI-125 has additional safety and efficacy advantages in terms of reduced respiratory depression (delta agonism) and reduced likability (kappa agonism) over currently available agonist and antagonist treatments. In this project, our objective is to demonstrate the feasibility of DPI-125 as a MAT agent. We intend to do this by identifying the lowest dose at which DPI-125 mitigates somatic signs of opioid withdrawal in a validated rodent model of morphine dependence. Current standard of care medications will be used as active comparators. It is anticipated that DPI-125 will be able to alleviate physiological symptoms of withdrawal, at potentially very low doses and with a rapid onset. This combined with its superior safety profile (reduced respiratory depression and abuse potential) would make it a highly valuable addition to the OUD armamentarium. Should efficacy of DPI-125 be equal or superior to that of methadone or buprenorphine, DMK Pharma will advance the clinical development of DPI-125 as a MAT for OUD with an intention to improve patient access, adherence, tolerance and treatment progress. Given that DPI-125 is a clinical stage asset, the potential of adding it to the MAT armamentarium for OUD could happen within just a few years of clinical development.

项目摘要 超过210万美国人患有阿片类药物使用障碍（OUD），每年导致47，000人死亡。 寻求治疗的个人必须处理耻辱，获得合格医疗保健专业人员的机会有限， 获得药物辅助治疗（MAT）的官僚主义障碍，此外还需要经历 MAT之前的戒断症状，所有这些加起来都是无效的访问系统。即使在治疗中， 患者面临着几个障碍，如疼痛，渴望，压力，羞耻，治疗不一致和复发， 保持有效的治疗方案。这只是实现长期目标所需的许多步骤之一。 禁欲和更稳定的生活。这条道路是痛苦的，而且这些选择很少 个人和治疗他们的医务人员。 DMK建议使用DPI-125扩展OUD的MAT能力，其中小分子，三重（μ，δ和 κ）阿片受体激动剂。实验、临床和理论证据表明DPI-125具有 在减少呼吸抑制（δ激动）方面的额外安全性和有效性优势， 与目前可用的激动剂和拮抗剂治疗相比，降低的亲和力（κ激动作用）。 在这个项目中，我们的目标是证明DPI-125作为MAT剂的可行性。我们打算这样做 通过确定DPI-125减轻阿片类药物戒断的躯体体征的最低剂量， 吗啡依赖的啮齿动物模型。当前标准治疗药物将用作活性药物 比较仪.预计DPI-125将能够减轻戒断的生理症状， 可能是很低的剂量并且发病迅速。这与其上级的安全性相结合（减少 呼吸抑制和滥用潜力）将使其成为OUD的一个非常有价值的补充 医疗设备DPI-125的疗效是否等于或上级于美沙酮或丁丙诺啡，DMK 制药公司将推进DPI-125作为OUD MAT的临床开发，旨在改善患者 可及性、依从性、耐受性和治疗进展。 鉴于DPI-125是一种临床阶段资产，将其添加到OUD的MAT医疗设备中的可能性可能 发生在临床发展的几年内。