A once-weekly oral methadone for maintenance therapy for opioid use disorder

每周一次口服美沙酮用于阿片类药物使用障碍的维持治疗

基本信息

批准号：
10455129
负责人：
Patrick Boen
金额：
$ 1169.98万
依托单位：
LYNDRA THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455129
关键词：
Address Alcohols Alzheimer&apos s Disease Amendment Animal Model Animals Biological Availability Cardiotoxicity Cessation of life Clinical Clinical Data Clinical Research Clinical Trials Cyclic GMP Data Development Directly Observed Therapy Dosage Forms Dose Drug Delivery Systems Drug Screening Ensure Evaluation FDA approved Fasting Formulation Future Goals Government HIV Health Services Accessibility Human Individual Injectable Inpatients Kinetics LYN gene Lead Life Lower Gastrointestinal Tract Malaria Methadone Naltrexone National Institute of Drug Abuse Opioid replacement therapy Oral Outcome Measure Outpatients Overdose Participant Patient-Focused Outcomes Patients Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Phase Process Production Provider Recovery Regimen Risk Safety Stomach Technology Therapeutic Therapeutic Agents Therapeutic Effect Toxic effect Treatment outcome Urine Visit Work barrier to care base clinical candidate clinical development clinical material compliance behavior drug release kinetics effectiveness evaluation efficacy study enantiomer first-in-human gastric retention healthy volunteer human study improved improved outcome innovation meetings methadone clinic/center methadone treatment novel opioid epidemic opioid therapy opioid use disorder patient safety preclinical development preclinical safety preclinical study prevent programs residence scale up social stigma socioeconomics treatment center treatment site treatment strategy

项目摘要

Methadone is an FDA-approved medication-assisted therapy (MAT) for opioid use disorder (OUD). Methadone maintenance therapy has been shown to facilitate recovery and prevent deaths. In the US methadone maintenance therapy currently involves once-daily drug administration at specially designated treatment sites (“methadone clinics”) under direct observation. Once-daily directly observed therapy presents difficulties for many patients and providers and contributes to the current treatment gap wherein only approximately 20% of patients with OUD are receiving MATs. Recent innovations in drug delivery technology, such as long-acting injectables, have not been applied to methadone delivery and methadone drug products are essentially identical to the immediate release products introduced several decades ago. NIDA has expressed a need for new treatment strategies for OUD to help address the current opioid crisis, including new formulations of existing medications such as methadone to improve treatment access and compliance and reduce diversion. This proposal is for development of a once-weekly oral methadone for maintenance therapy for OUD. Lyndra has developed an oral gastric residence dosage form that has been demonstrated to provide at least seven days of continuous delivery of many different therapeutic agents, including drugs for treatment of Alzheimer’s disease, HIV and malaria. Lyndra’s technology has been validated in multiple large animal models and is currently in clinical trials. A once-weekly oral methadone product could (1) lower a major barrier to treatment for many patients, (2) reduce the stigma and socioeconomic impact of MMT, and (3) increase the capacity of methadone treatment centers by reducing the number of patient visits. The UG3 phase of this proposal is for two years of pharmaceutical development and pharmacological characterization of a once-weekly oral methadone dosage form, leading to the selection of a clinical candidate for a first-in-human trial and submission of an IND. In Aim 1, dosage form development and optimization will be pursued to achieve target values for drug load, release kinetics and PK profile. Aim 2 will focus on IND- enabling activities leading to submission of an IND for a first-in-human clinical trial. Once-weekly methadone dosage form process development and scale-up, shelf life studies, clinical manufacturing and GLP toxicity studies will be performed. The UH3 phase of the proposal includes clinical trials to evaluate the safety and PK of the once-weekly oral methadone dosage form in subjects with OUD who are currently maintained on once- daily methadone. The gating milestone for transition to the UH3 phase is acceptance of the IND by the FDA. Lyndra Inc Confidential Page 1

美沙酮是由FDA批准的阿片类药物使用障碍（OUD）的药物辅助治疗（MAT）。美沙酮维持治疗已被证明可以促进康复和预防死亡。在美国的Metagadone 维护治疗目前涉及在专门指定的治疗部位每天一次的药物管理（“美沙酮诊所”）在直接观察下。每天一次直接观察到的治疗给人带来困难许多患者和提供者为当前的治疗差距做出了贡献，其中约有20％ OUD患者正在接受垫子。药物输送技术的最新创新，例如长效注射剂，尚未应用于Metagadone递送，而Metagadone药物本质上是与几十年前推出的直接发行产品相同。 NIDA表示需要 OUD的新治疗策略，以帮助解决当前的阿片类药物危机，包括现有的药物，例如改善治疗访问和依从性并减少转移的药物。该建议是为了开发一次每周一次的口服方法辅导酮，用于OUD维护治疗。 Lyndra 已经开发了一种口服胃居住剂量，已证明至少提供七个连续交付许多不同治疗剂的天数，包括治疗阿尔茨海默氏症的药物疾病，艾滋病毒和疟疾。 Lyndra的技术已在多个大型动物模型中得到了验证，并且目前正在临床试验中。每周一次的口服方法可以（1）降低治疗的主要障碍对于许多患者，（2）减少了MMT的污名和社会经济影响，（3）增加了能力 Metagadone治疗中心通过减少患者就诊次数。该提案的UG3阶段是为期两年的药物开发和药理学一个每周一次的口服Methetadone剂型的表征，导致选择临床候选者进行首次人类试验和提交IND的提交。在AIM 1中，剂型的开发和优化将是追求以实现药物负荷，释放动力学和PK概况的目标值。 AIM 2将重点放在启用活动，导致提交IND进行首次人类临床试验。每周一次的方法adone 剂型形式的过程开发和扩大规模，保质期研究，临床制造和GLP毒性将进行研究。该提案的UH3阶段包括评估安全性和PK的临床试验在与OUD的受试者中曾经每周一次的口服Methetadone剂型中，他们目前维持一次每日方法adone。过渡到UH3阶段的门控里程碑是FDA对IND的接受。 Lyndra Inc机密第1页