Objective:

To assess the safety and pharmacokinetics (PK) of single intramuscular (IM) doses of IVL3004 compared with Vivitrol® (380mg) in healthy male subjects.

Background:

Design/Methods:

This was a Phase 1, open-label, single-ascending dose study (Part A). Thirty-four healthy non-smoking males (18–55 years) were assigned to: Cohort 1 (Vivitrol®;380mg, n=10), Cohort 2 (IVL3004;300mg, n=12), and Cohort 3 (IVL3004;380mg, n=12). Plasma naltrexone concentrations were measured up to 672h post-dose using validated LC-MS/MS, and PK parameters were calculated by non-compartmental analysis.

Results:

Median Tmax was delayed with IVL3004 (336h and 240h vs 48h for the reference), accompanied by lower Cmax values (41% and 58% of the reference). Despite lower peaks, both IVL3004 doses maintained plasma concentration > 1 ng/ml at Day 28 (672h), a threshold considered clinically effective. IVL3004 380 mg achieved nearly equivalent AUC to Vivitrol®, while 300mg dose also sustained effective concentrations. Thus, IVL3004 maintained desired therapeutic exposure over 4 weeks with reduced Cmax and lower total dose, potentially improving safety profile. Adverse events (AEs) occurred in 33/34 subjects (97%), predominantly mild. Injection-site reaction frequency was similar, but mean duration was shorter with IVL3004 (3.8 and 4.9 days) versus Vivitrol® (18.2 days). No severe/serious AEs were reported, supporting favorable tolerability of IVL3004.

Conclusions:

IVL3004 demonstrated sustained-release PK with delayed Tmax and extended exposure. Even at 300mg, therapeutic plasma concentrations were maintained throughout 28 days, achieving target exposure comparable to Vivitrol®. Controlled initial release minimized early burst, reflecting advanced formulation technology. Together with shorter injection-site reaction duration versus Vivitrol®, these PK features support IVL3004 as a safer, more effective long-acting naltrexone option with potential to improve patient adherence and quality of life.