Pharmacokinetics, safety and tolerability of long‐acting parenteral intramuscular injection formulations of doravirine.

What is known and objective: Doravirine is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus (HIV)‐1 infection. This phase 1 study in healthy adults investigated the pharmacokinetics, safety and tolerability of long‐acting parenteral (LAP) microsuspension formulations of doravirine administered as an intramuscular (IM) injection. Methods: After confirmation of tolerability and safety of oral doravirine, 36 participants were randomized 1:1:1 to receive IM doravirine 200 mg as Treatment A (1 × 1 mL, 20% [200 mg/mL] suspension), B (1 × 0.66 mL, 30% [300 mg/mL] suspension) or C (2 × 0.5 mL, 20% suspension). Blood samples were taken as venous plasma, venous dried blood spots (DBS) and fingerstick DBS. Results and discussion: Plasma concentration‐time profiles following IM treatments demonstrated rapid initial doravirine release, with initial peak ~4 days post‐injection, followed by decline over the next ~6 days; a second peak was reached at ~24‐36 days, corresponding to prolonged and sustained release, with measurable concentrations up to Day 183. Treatment C was associated with highest peak concentrations and shortest time to maximum concentration. Elimination half‐lives for all IM formulations were prolonged versus oral administration (~46‐58 days vs ~11‐15 hours). Oral doravirine and IM doravirine were generally well tolerated; injection‐site pain was the most common adverse event for IM doravirine. Doravirine concentrations from DBS samples showed strong correlations to venous plasma concentrations. What is new and conclusions: Novel doravirine LAP IM injection formulations investigated in this study demonstrated sustained plasma doravirine concentrations over a course of >20 weeks. [ABSTRACT FROM AUTHOR]