Methadone Dosing System (MDS) - One of the biggest obstacles for patients seeking to break an opioid addiction is overcoming their physical dependence on the drug, which can cause extreme withdrawal symptoms, including nausea, diarrhea, bone and muscle pain, tachycardia, hypertension, fever, and chills. Relief from withdrawal symptoms is a common cause for patient relapse, and the fear of a negative withdrawal experience is a major barrier to voluntary discontinuation of opioid use (Pergolizzi 2020). Methadone is a commonly prescribed medication for opioid use disorders (OUDs) that has been shown to decrease mortality and improve OUD treatment retention (Suen 2022, Santos 2021), but anywhere from 30% to 80% of patients receiving methadone maintenance treatment (MMT) respond poorly to treatment (Fonseca et al., 2011). A major reason for this wide range of response is the genetic variability of metabolism. Slow metabolism can lead to drug accumulation and negative side effects, while high metabolism can rapidly deplete therapeutic concentrations of methadone and lead to withdrawal and/or additional drug use (Kharasch, 2017). Individual metabolic differences can result in a 17-fold variation in methadone serum levels for a given dose (Eap et al., 2002), yet current practice is to follow a general algorithm for methadone dose adjustments that restricts dose increases to 5 to 10 mg without regard for metabolism. This proposed FastTrack project aims to develop and commercialize a new science-based approach for methadone dosing adjustments that uses novel, non-invasive point-of-care technology to evaluate small blood samples taken from patients using the well-established finger prick method and quickly evaluate the methadone rate of metabolism via a proprietary sensor to enable better, individualized methadone dosing decisions. In Phase I of the project, we will demonstrate the technical feasibility to accurately detect and measure methadone levels in a small validation study with screen printed electrode-based sensors. In Phase II of the project, we will confirm those results by developing a proof- of-concept device to conduct a small-scale feasibility study that will inform the design of the commercial version. A pre-pivotal clinical study with the commercial-grade device will then be conducted to evaluate device performance. This will be followed by a clinical trial pivotal study to correlate the commercial-grade device’s methadone metabolism measurements with the current gold standard, the cumbersome and untimely trough and peak analysis. Additional activities will take place to prepare the CARI system for regulatory clearance. If successful, the CARI solution has the potential to dramatically improve the benefit-risk profile of MMT treatment by providing methadone dosing guidance that is much faster, less onerous, and more widely adopted than currently used methods. With more accurate metabolism-informed methadone dosing for OUD treatment, it is expected that patients will experience fewer withdrawal systems, improving their perception of care and patient retention rates, thereby reducing the rates of relapse and overdose.
