Abstract: This single‐center, double‐blind, placebo‐controlled, sequential‐group phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of mavatrep (JNJ‐39439335), a transient receptor potential vanilloid 1 antagonist, in healthy Japanese and caucasian subjects. In part 1, a single‐ascending‐dose study, 50 subjects (25 each healthy Japanese and caucasians) were enrolled and received a single oral dose of 10, 25, or 50 mg mavatrep. Caucasian subjects were matched to Japanese subjects with respect to age (±5 years) and body mass index (±5 kg/m2). In part 2, a multiple‐ascending‐dose study, 36 Japanese subjects were enrolled and received once‐daily oral doses of 10, 25, or 50 mg of mavatrep for 21 days. The single‐dose PK of mavatrep and its metabolites was similar in the Japanese and caucasian subjects after adjustment of body weight. Following multiple dosing in Japanese subjects, a steady‐state condition was reached in approximately 14 days. M2 and M3 are major circulating metabolites with mean exposure > 10% of mavatrep. Nonrenal clearance was the major route of elimination for mavatrep, M2, and M3. Mavatrep exhibited a long half‐life, ranging from 68 to 101 and 82–130 hours for Japanese and caucasian subjects, respectively. After single and multiple dosing, mavatrep was well tolerated. The most common adverse events observed were thermohypoesthesia, feeling cold, chills, and feeling hot. Mavatrep and its metabolites exhibited similar PK profiles after single ascending doses in healthy Japanese and caucasian men. [ABSTRACT FROM AUTHOR]