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Clinical Trial
. 2026 Feb 4;70(2):e0126125.
doi: 10.1128/aac.01261-25. Epub 2026 Jan 14.

First-in-human safety and pharmacokinetics of MK-7602, the antimalarial inhibitor of plasmepsins IX/X, in single- and multiple-ascending-dose studies

Susan E Stanley  1 , Russ P Carstens  1 , Maria V Liberti  1 , Ward Eertmans  2 , Myrthel Vranckx  2 , Diane Longo  1 , Nairita Ghosal  1 , Marissa Vavrek  1 , David B Olsen  1 , Alan F Cowman  3 , Tom Reynders  2 , Caroline Cilissen  2 , Tine Laethem  2 , Sylvie Rottey  4 , Jonathan A Robbins  1 , S Aubrey Stoch  1 , Jesse Nussbaum  1
Affiliations
Clinical Trial

First-in-human safety and pharmacokinetics of MK-7602, the antimalarial inhibitor of plasmepsins IX/X, in single- and multiple-ascending-dose studies

Susan E Stanley et al. Antimicrob Agents Chemother. .

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 (Tmax) was 1.5-3.0 h, with dose-proportional increases in maximum concentration (Cmax) and the area under the curve over the dosing interval (AUC0-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 Cmax 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.

Keywords: MK-7602; antimalarial drug; malaria; plasmepsin IX; plasmepsin X.

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Conflict of interest statement

S.E.S., R.P.C., D.B.O., C.C., D.L., J.N., M.V.L., N.G., T.L., T.R., and W.E. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A.F.C. is the lead investigator of the WEHI team that discovered and developed MK-7602 in collaboration with Merck & Co., Inc., Rahway, NJ, USA, and has received grants from the Wellcome Trust for studies on MK-7602, and for attending meetings and giving invited seminars. S.R. has received consulting fees and support for attending meetings and/or travel from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J.A.R. and S.A.S. were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA during clinical conduct, receiving salary and holding equity at that time. The other authors did not report any conflict of interest.

Figures

Fig 1
Fig 1
An overview of the malaria parasite life cycle demonstrating the three-stage inhibition potential of MK-7602. The biochemical targets for MK-7602, plasmepsin IX (PMIX), and plasmepsin X (PMX) are expressed in the liver, blood, and sexual (transmission or mosquito) stages of the replication cycle.
Fig 2
Fig 2
Study design of 7602-001. (A) Part 1 and (B) part 2. All doses of MK-7602 were administered as single doses, except for in panel B, period 4. Study 7602-001 part 1 included three panels—A, B, and D—in all of which participants were randomized (6:2) to receive MK-7602 (n = 6) or placebo (n = 2). Study 7602-001 part 2 was conducted with panel C as an open-label panel (n = 12). aMK-7602 400 mg was administered as a split dose of two doses of 200 mg Q12H. PK, pharmacokinetics; Q12H, every 12 h; Q24H, every 24 h.
Fig 3
Fig 3
Study design of 7602-002. Each panel had eight participants randomized (3:1) to receive MK-7602 (n = 6) or placebo (n = 2). aIntensive PK sampling occurred on day 1, day 3 (panel A only), and day 7. bDay 7 intervention was administered in the morning. cIntensive PK sampling occurred on day 1, day 3, and day 7 for panel D. PK, pharmacokinetics; Q12H, every 12 h; Q24H, every 24 h.
Fig 4
Fig 4
Arithmetic mean (± SD) concentration–time profiles of MK-7602 following administration of a single oral dose of MK-7602 to healthy adult male participants under fasted and fed states in panel A, linear scale. Insert: semi-log scale. SD, standard deviation.
Fig 5
Fig 5
(A) Arithmetic mean (± SD) plasma concentration–time profiles of MK-7602 following administration of oral single-ascending doses of MK-7602 to healthy men in panel A, panel B, and panel D of study 7602-001, part 1, linear scale. Insert: semi-log scale. (B) Arithmetic mean (± SD) plasma concentration–time profiles of MK-7602 after split oral doses of MK-7602 400 mg (200 mg Q12H) to healthy men in panel B of study 7602-001, part 1, linear scale. Insert: semi-log scale. Q12H, every 12 h; SD, standard deviation.
Fig 6
Fig 6
Arithmetic mean (± SD) plasma concentration–time profiles of MK-7602 following administration of multiple oral doses of MK-7602 to healthy participants in panels A, B, C, D, and E in study 7602-002. (A) Linear scale, (B) semi-log scale. aDay 7 concentration data were not available for one participant in panel E. Q12H, every 12 h; Q24H, every 24 h; SD, standard deviation.
Fig 7
Fig 7
Arithmetic mean (± SD) concentration–time profiles of MK-7602 following administration of a single oral dose of MK-7602 alone and coadministered with itraconazole to healthy adult male participants in panel C, linear scale. Insert: semi-log scale. SD, standard deviation.
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