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
Improved pharmacologic options for medication-assisted therapy (MAT) of opioid use disorder (OUD) are needed. The goal of the proposed program is the preclinical development and clinical proof of concept of an oral once-weekly therapy for OUD incorporating methadone into a Lyndra dosage form. Successful completion of this project will yield clinical data demonstrating a novel MAT that may overcome barriers to treatment and improve outcomes for patients with OUD.
