Odanacatib Pharmacokinetics Comparison Between Chinese and Non-Chinese Postmenopausal Women.

ABSTRACT

Odanacatib (ODN), an oral selective inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this phase 1 open-label study, 12 healthy Chinese postmenopausal women received single-dose ODN 50 mg on day 1 and multiple-dose ODN 50 mg once weekly on days 15, 22, 29, and 36 under fasted conditions. Pharmacokinetic (PK) parameters were evaluated on days 1 and 36. Multiple-dose area under the concentration-time profile (AUC0-168h ) and maximum plasma concentration (Cmax ) were compared with historical data from 9 non-Chinese postmenopausal women who also received ODN 50 mg once weekly for 4 weeks. Median time to Cmax (tmax ) was 3 and 4 hours following single- and multiple-dose administration, respectively. The arithmetic mean ± SD terminal half-life was 81.0 ± 14.0 and 106.7 ± 14.4 hours following single- and multiple-dose administration, respectively. Comparison of multiple-dose PK parameters showed that the geometric mean ratios (Chinese/non-Chinese) and 95%CIs for AUC0-168h and Cmax were 0.81 (0.55-1.19) and 0.87 (0.69-1.11), respectively. All adverse events were mild, none were serious, and none led to discontinuation. Single- and multiple-dose PKs of ODN 50 mg in Chinese postmenopausal women were generally similar to those previously reported in non-Chinese postmenopausal women.