Effect of the Cathepsin K Inhibitor Odanacatib on Bone Resorption Biomarkers in Healthy Postmenopausal Women: Two Double-Blind, Randomized, Placebo-Controlled Phase I Studies
| Autor: | K Van Dyck, Boyd B. Scott, M De Decker, Stefan Zajic, Maria Gutierrez, Q Liu, Keith Gottesdiener, Deborah Panebianco, Deborah L. Miller, L Liu, Julie A. Stone, Le T. Duong, Bo Jin, SA Stoch, John A. Wagner |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Cathepsin K Administration Oral Placebo Collagen Type I Drug Administration Schedule Bone resorption chemistry.chemical_compound Double-Blind Method Pharmacokinetics N-terminal telopeptide Internal medicine medicine Humans Pharmacology (medical) Bone Resorption Osteoporosis Postmenopausal Aged Pharmacology Creatinine business.industry Biphenyl Compounds Middle Aged Cathepsins Peptide Fragments Treatment Outcome Endocrinology chemistry Female Peptides business human activities Biomarkers Procollagen Odanacatib Type I collagen |
| Zdroj: | Clinical Pharmacology & Therapeutics. 86:175-182 |
| ISSN: | 1532-6535 0009-9236 |
| Popis: | 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 dosesor = 25 mg and daily dosesor = 2.5 mg. |
| Databáze: | OpenAIRE |
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