Safety, tolerability and pharmacokinetic profile of single and multiple oral doses of arterolane (RBx11160) maleate in healthy subjects

Arterolane (RBx11160, OZ277) maleate is a rapidly acting synthetic trioxolane anti‐malarial. This randomized, placebo controlled study was a phase I study to evaluate the clinical safety and tolerability as well as pharmacokinetics (PKs) of arterolane maleate including food effect. Eight single rising oral doses of arterolane (25, 50, 100, 150, 200, 300, 400, 600 mg), food effect under fed and fasting conditions at 100 mg dose and four multiple oral dose regimens (25, 50, 100, 200 mg) were administered once daily for 7 days in 64 healthy young males (Caucasian). A randomized, placebo‐controlled study was also conducted in healthy elderly males and females (Caucasian) to investigate PKs, safety and tolerability of single oral dose (100 mg) of arterolane. All doses were well tolerated after oral administration. The initial peak of arterolane was apparent at 2–3 hours post‐dose followed by a secondary peak at approximately 5 hours post‐dose. Thereafter, plasma arterolane concentration declined with a geometric mean t1/2 of approximately 2–4 hours. The PKs of arterolane appeared to be time‐invariant after repeated once‐daily dosing. The incidence of adverse events was similar for placebo and active treatments. Arterolane had similar PKs and tolerability in elderly and younger subjects and between elderly males and females.