Semi-mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine Bone Mineral Density in Two Phase II Studies of Postmenopausal Women

Authors: Stone J, Jaworowicz DJ, Zajic S, Leung A, Duong LT, Passarell JA, Fiedler-Kelly J, Cohn D, Verbruggen N, Stoch A
Conference: International Symposium on Measurement and Kinetics of in vivo Drug Effects
Keywords: 1-compartment, biomarker, BSAP, dose-ranging, dose-response, exposure, geriatrics, Hill function, indirect response, Japanese, linear, LS-BMD, MK-0822, orthopedics, osteoclast, osteoporosis, resorption, saturable, turnover, uNTx, visual predictive check
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

Odanacatib (MK-0822), a potent, orally-active inhibitor of cathepsin K, is under clinical development for treatment of postmenopausal osteoporosis. This poster describes base model development of a semi-mechanistic model of bone turnover to describe creatinine adjusted urinary aminoterminal crosslinked telopeptides of Type I collagen (uNTx), a bone resorption biomarker, and lumbar spine bone mineral density (LS-BMD) data from two Phase II dose-ranging studies during and after treatment with odanacatib.

International Symposium on Measurement and Kinetics of In Vivo Drug Effects, Noordwijkerhout, The Netherlands, April 2010

By Julie A. Stone, David Jaworowicz, Stefan Zajic, Albert Leung, Le Thi Duong, Julie Passarell, Jill Fiedler-Kelly, Dosinda Cohn, Nadia Verbruggen, and Aubrey Stoch