Semi-mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine and Distal Forearm Bone Mineral Density in a Phase IIb Study of Postmenopausal Women

Authors: Zajic S, Stone J, Jaworowicz DJ, Leung A, Duong LT, Passarell JA, Fiedler-Kelly J, Cohn D, Verbruggen N, Stoch A
Conference: PAGE
Keywords: 1-compartment, biomarker, BMD, bone mineral density, BSAP, dose-response, empirical, functional forms, indirect response model, inhibitory sigmoid Emax function, linear elimination, lumbar spine, MK-0822, ODN, orthopedics, osteoclast, osteoporosis, P1NP, Phase 2, placebo, rate limiting, resorption, resorptive, saturable bioavailability with dose, turnover, uNTx
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 and distal forearm bone mineral density (LS- and DF-BMD) data from a Phase IIb dose-ranging study during and after treatment with odanacatib.

Population Approach Group in Europe (PAGE), Athens, Greece, June 2011

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