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.
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Authors | S 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 |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 86
Issue 2
Pg. 175-82
(Aug 2009)
ISSN: 1532-6535 [Electronic] United States |
PMID | 19421185
(Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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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
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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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