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

## TL;DR

This study shows that MK-7602, a new malaria drug, is safe and has predictable drug levels in the body after single and multiple doses.

## Contribution

The study provides first-in-human evidence of MK-7602's safety and pharmacokinetics, supporting its further development for malaria treatment.

## Key findings

- MK-7602 was generally well tolerated with headaches as the most common adverse event.
- Drug levels increased proportionally with dose and reached steady-state concentrations by day 3.
- Coadministration with itraconazole significantly increased MK-7602's concentration in the blood.

## 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.