Objectives: iSTEP-N is a novel, bioresorbable, subcutaneous implant designed to release naltrexone for 6–12 months after a single procedure and improve adherence. This first-in-human study evaluated the safety and pharmacokinetics of iSTEP-N. Methods: This was a single-center, randomized, double-blind, placebo-controlled, single-ascending-dose trial. Sixteen healthy adults (6 females and 10 males) were assigned to receive either 1 implant (4.8 g naltrexone), 2 implants (9.6 g naltrexone), or placebo implants. Participants were followed for 12 weeks, after which implants were removed per regulatory requirement. Plasma naltrexone concentrations and safety outcomes were assessed throughout. Results: All participants completed the study. The 9.6 g cohort maintained mean plasma naltrexone concentrations above the 2.0 ng/mL opioid blockade threshold from Tmax at 10 hours through the end of the study at 12 weeks; no mean value fell below 2.8 ng/mL during this time. The 4.8 g cohort maintained therapeutic levels of naltrexone through week 6 but dropped below threshold thereafter. In both cohorts, ∼22% of implant drug content was released over 12 weeks, based on plasma exposure and estimated clearance, indicating potential for extended coverage. In the 9.6 g group, seroma formation was observed in 3 of 6 participants (50%) and resolved without intervention. No serious adverse events occurred. Conclusions: At the 9.6 g dose, iSTEP-N provided sustained therapeutic naltrexone exposure for 12 weeks with a favorable safety profile, while releasing less than one-fourth of its drug content. Further studies will evaluate longer-term exposure, safety, and clinical feasibility in individuals with opioid use disorder.
Cohen et al. (Mon,) studied this question.