A Long-acting Naltrexone Implant (iSTEP-N) for Opioid Use Disorder: First-in-Human Phase I Trial

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Clinical Trials

Background:

• Opioid use disorder (OUD) is a significant public health crisis.
• Naltrexone is an effective opioid antagonist but adherence to daily oral formulations is challenging.
• Novel delivery systems are needed to improve long-term naltrexone adherence and treatment outcomes.

Purpose of the Study:

• To evaluate the safety and pharmacokinetics of iSTEP-N, a novel bioresorbable subcutaneous naltrexone implant.
• To assess naltrexone release profiles and plasma concentrations over 12 weeks.
• To determine the potential for iSTEP-N to provide sustained therapeutic naltrexone exposure.

Main Methods:

• A single-center, randomized, double-blind, placebo-controlled, single-ascending-dose trial was conducted.
• Sixteen healthy adults received either 4.8g naltrexone implant, 9.6g naltrexone implant, or placebo.
• Safety outcomes and plasma naltrexone concentrations were monitored for 12 weeks.

Main Results:

• The 9.6g iSTEP-N dose maintained plasma naltrexone above the 2.0 ng/mL opioid blockade threshold for 12 weeks.
• The 4.8g dose provided therapeutic levels for 6 weeks.
• Approximately 22% of implant drug content was released over 12 weeks; no serious adverse events were reported, though 50% of the 9.6g group experienced transient seroma.

Conclusions:

• The 9.6g iSTEP-N implant demonstrated sustained therapeutic naltrexone exposure for 12 weeks with a favorable safety profile.
• The implant released less than one-fourth of its drug content, suggesting potential for longer duration of action.
• Further research is warranted to assess long-term efficacy, safety, and feasibility in OUD patients.