1. MIJ821 (onfasprodil) in healthy volunteers: First‐in‐human, randomized, placebo‐controlled study (single ascending dose and repeated intravenous dose)
- Author
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Baltazar Gomez‐Mancilla, Jeffrey A. Levy, Subramanian Ganesan, Thomas Faller, Gil Issachar, Ziv Peremen, Offir Laufer, Revital Shani‐Hershkovich, Kostas Biliouris, Ela Walker, Mark P. Healy, Oleksandr Sverdlov, Sachin Desai, S. Nassir Ghaemi, Jang‐Ho Cha, and Y. Gopi Shanker
- Subjects
Therapeutics. Pharmacology ,RM1-950 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract This single‐center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40‐min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUCinf values of MIJ821 increased in a dose‐proportional manner across the dose range 0.016–0.48 mg/kg and the Cmax values in a slight overproportional manner across the dose range 0.048–0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUCinf was 708 h ng/mL and the geometric mean Cmax was 462 ng/mL. Inspection of 1‐h post‐dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose‐dependent.
- Published
- 2023
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