First-in-human safety and pharmacokinetics of MK-7602, the antimalarial inhibitor of plasmepsins IX/X, in single- and multiple-ascending-dose studies
- Author(s)
- Stanley, SE; Carstens, RP; Liberti, MV; Eertmans, W; Vranckx, M; Longo, D; Ghosal, N; Vavrek, M; Olsen, DB; Cowman, AF; Reynders, T; Cilissen, C; Laethem, T; Rottey, S; Robbins, JA; Stoch, SA; Nussbaum, J;
- Journal Title
- Antimicrobial Agents and Chemotherapy
- Publication Type
- Jan 14
- Abstract
- MK-7602 is a first-in-class dual-plasmepsin inhibitor being developed to treat malaria. Safety, tolerability, and pharmacokinetics (PK) of MK-7602 following single and multiple doses were evaluated in two phase 1 studies (7602-001; 7602-002). Study 7602-001 included two parts: part 1, a randomized, single-ascending-dose (10-400 mg), placebo-controlled, double-blind study (n = 24); and part 2, a non-randomized, fixed-sequence, open-label study (n = 12) to assess the effect of itraconazole (200 mg), a cytochrome P450 3A and P-glycoprotein inhibitor, on the PK of MK-7602 (25 mg). Study 7602-002 was a randomized, placebo-controlled, multiple-ascending-dose study (n = 40); participants received MK-7602 (50-300 mg) or placebo for 7 days. Single and multiple doses of MK-7602 were generally well tolerated. Headaches were the most common adverse event (7602-001 part 1: 54.5%; 7602-002: 36.7%). MK-7602 median time to maximal concentration (T(max)) was 1.5-3.0 h, with dose-proportional increases in maximum concentration (C(max)) and the area under the curve over the dosing interval (AUC(0-tau)) at single and multiple doses of ≥50 mg. Terminal half-life was 31.3-41.4 h following multiple dosing, the accumulation ratio for daily dosing was 1.03-2.20, and steady-state concentrations were reached by day 3. Coadministration with itraconazole resulted in a 6- and 12-fold increase in C(max) and area under the concentration-time curve to infinity, respectively. The primary hypothesis that a well-tolerated dose of MK-7602 would achieve a trough concentration of ≥0.017 μM was met in both studies. Safety and PK characteristics support continued development of MK-7602.
- Publisher
- ASM
- Keywords
- Mk-7602; antimalarial drug; malaria; plasmepsin IX; plasmepsin X
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 41532789
- Publisher's Version
- https://doi.org/10.1128/aac.01261-25
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-29 02:00:46
Last Modified: 2026-01-29 02:01:03