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Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies.

Abstract
Inhibition of cathepsin K (CatK) is a potential new treatment for osteoporosis. In two double-blind, randomized, placebo-controlled phase I studies, postmenopausal female subjects received odanacatib (ODN), an orally active, potent, and selective CatK inhibitor, once weekly for 3 weeks or once daily for 21 days. Bone turnover biomarkers, safety monitoring, and plasma ODN concentrations were assessed. These studies showed ODN to be well tolerated. Pharmacokinetic (PK) analysis revealed a long half-life (t(1/2); 66-93 h) consistent with once-weekly dosing. Pronounced reductions in C-terminal telopeptide of type I collagen (approximately 62%) and N-terminal telopeptide of type I collagen normalized to creatinine (NTx/Cr) (approximately 62%) at trough (C(168 h)) were seen following weekly administration. Robust reductions in CTx (up to 81%) and NTx/Cr (up to 81%) were seen following daily administration. ODN exhibits robust and sustained suppression of bone resorption biomarkers (CTx and NTx/Cr) at weekly doses > or = 25 mg and daily doses > or = 2.5 mg.
AuthorsS A Stoch, S Zajic, J Stone, D L Miller, K Van Dyck, M J Gutierrez, M De Decker, L Liu, Q Liu, B B Scott, D Panebianco, B Jin, L T Duong, K Gottesdiener, J A Wagner
JournalClinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 86 Issue 2 Pg. 175-82 (Aug 2009) ISSN: 1532-6535 [Electronic] United States
PMID19421185 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Biphenyl Compounds
  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K
  • odanacatib
Topics
  • Administration, Oral
  • Aged
  • Biomarkers (blood)
  • Biphenyl Compounds (administration & dosage, adverse effects, pharmacokinetics, pharmacology, therapeutic use)
  • Bone Resorption (blood, drug therapy)
  • Cathepsin K
  • Cathepsins (antagonists & inhibitors)
  • Collagen Type I
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal (drug therapy)
  • Peptide Fragments (blood)
  • Peptides
  • Procollagen (blood)
  • Treatment Outcome

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