Title : A Long-Acting Naltrexone Implant (for Opioid Use Disorder: First-in-Human Phase I Trial)
Abstract:
Background: Extended-release intramuscular naltrexone (XR-NTX; Vivitrol®) reduces relapse risk in opioid use disorder (OUD), but real-world adherence is only about 10 percent at 6 months. One reason for poor adherence is the decline in plasma NTX levels to below therapeutic levels (> 2 ng/ml) that occurs in some patients late in the dosing cycle. A longer-acting NTX formulation may improve adherence and therapeutic coverage. BIOPIN is a novel, bioabsorbable subcutaneous implant designed to achieve therapeutic plasma NTX levels for 6–12 months following a single administration.
Methods: In this randomized, double-blind, placebo-controlled Phase 1 trial, two sequential cohorts of healthy volunteers received either one BIOPIN (4.8 g naltrexone), two BIOPINs (9.6 g total), or placebo (6:2 ratio per cohort). Participants were followed for 12 weeks with serial pharmacokinetic sampling and safety assessments. Per FDA requirement, implants were explanted at Week 12.
Results: All sixteen participants (mean age 32 years; mean BMI 28 kg/m²) completed the study. The subjects in the 9.6 g dose cohort maintained mean plasma naltrexone concentrations of greater than 2.5 ng/mL at all time points. The subjects in the 4.8 g dose cohort’s mean plasma naltrexone levels declined below threshold after Week 7. At explantation, only 22% of implant drug content was released, consistent with the potential for 6–12 months of therapeutic exposure. BIOPIN was well tolerated, with no serious adverse events and only mild, transient implant-site reactions.
Conclusions: The 9.6 g BIOPIN NTX implant achieved sustained therapeutic plasma NTX exposure for 3 months with an excellent safety profile, supporting its potential as a treatment to improve adherence and reduce relapse in patients with OUD. It has been granted Fast-Track designation by the FDA. Longer-term studies are underway to confirm extended duration of action and clinical effectiveness.
