873140 is a novel CCR5 antagonist with potent in vitro anti-human immunodeficiency virus (HIV) activity. This study was a double-blind, randomized, placebo-controlled, single- and repeat-dose escalation investigation of the safety, pharmacokinetics, and food effect of 873140 in 70 adult subjects. During single-dose escalation, three cohorts (each composed of 10 subjects, with 8 subjects receiving the active drug and 2 subjects receiving the placebo [8 active and 2 placebo]) received doses of 50, 200, 400, 800, and 1,200 mg after an overnight fast, or 400 mg plus a standard high-fat breakfast in an alternating panel design. During repeat-dose escalation, four cohorts (each with 8 active and 2 placebo) received doses of 200, 400, 600, or 800 mg every 12 h (BID) for 8 days. Laboratory safety tests, vital signs, and electrocardiograms (ECGs) were performed at regular intervals, and blood samples were obtained for pharmacokinetics. Single and repeat doses of 50 mg to 800 mg were well tolerated, with no serious adverse events and no grade 3 or 4 adverse events. The mild-to-moderate side effects were primarily gastrointestinal and included abdominal cramping, nausea, and diarrhea. No specific trends in laboratory parameters or clinically significant ECG changes were noted. Plasma 873140 concentrations increased rapidly; the median time to maximum concentration of drug in serum was 1.75 to 5 h. The median area under the plasma concentration-time profile (AUC) and the maximum concentration of drug in serum (C(max)) ranged from 127 ng.h/ml and 24 ng/ml at 200 mg BID to 329 ng.h/ml and 100 ng/ml at 800 mg BID, respectively. Food consumption increased the AUC and C(max) by a mean of 1.7- and 2.2-fold, respectively. The pharmacokinetic and safety profile supports the continued investigation of 873140 with HIV-infected subjects.