Serum and urine bone resorption markers and pharmacokinetics of the cathepsin K inhibitor ONO-5334 after ascending single doses in post menopausal women

British Journal of Clinical Pharmacology

Volumn 74, Issue 6, 2012, Pages 959-970

  Nagase, Shinichi ^a   Hashimoto, Yoshitaka ^b   Small, Maria ^a   Ohyama, Michiyo ^a   Kuwayama, Tomohiro ^a   Deacon, Steve ^a  

^a ONO PHARMACEUTICAL CO   (Japan)

^b Pharmacokinetic Research Group   (Japan)

Author keywords

Bone resorption; Cathepsin K inhibitor; ONO 5334; Osteoporosis; Pharmacodynamics; Pharmacokinetics

Indexed keywords

AMINO TERMINAL TELOPEPTIDE; CARBOXY TERMINAL TELOPEPTIDE; CATHEPSIN K INHIBITOR; N [3 [2 (3,4 DIMETHYL 1,3 THIAZOLIDIN 2 YLIDENE)HYDRAZINO] 2,3 DIOXO 1 (TETRAHYDRO 2H PYRAN 4 YL)PROPYL]CYCLOHEPTANECARBOXAMIDE; ONO 5334; PHARMACOLOGICAL BIOMARKER; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BONE ATROPHY; BONE TURNOVER; COHORT ANALYSIS; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAM; FEMALE; FLATULENCE; FOOD; FOOD DRUG INTERACTION; HARD FECES; HEADACHE; HUMAN; LABORATORY TEST; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PHYSICAL EXAMINATION; POSTMENOPAUSE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN URINE LEVEL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SOMNOLENCE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN; VOMITING;

ADMINISTRATION, ORAL; AGED; AREA UNDER CURVE; BIOLOGICAL MARKERS; BONE RESORPTION; CATHEPSIN K; COLLAGEN TYPE I; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MIDDLE AGED; OSTEOPOROSIS, POSTMENOPAUSAL; PEPTIDES; POSTMENOPAUSE; THIAZOLIDINES;

EID: 84869011778     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2012.04307.x     Document Type: Article

References (19)

1. Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 2010; 95: 1555-65.
2. Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res 2007; 22: 487-94.
3. Berti PJ, Storer AC. Alignment/phylogeny of the papain superfamily of cysteine proteases. J Mol Biol 1995; 246: 273-83.
4. Nishi Y, Atley L, Eyre DE, Edelson JG, Superti-Furga A, Yasuda T, Desnick RJ, Gelb BD. Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res 1999; 14: 1902-8.
5. Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science 1996; 273: 1236-8.
6. Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, Moritz JD, Schu P, von Figura K. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A 1998; 95: 13453-8.
7. Gowen M, Lazner F, Dodds R, Kapadia R, Feild J, Tavaria M, Bertoncello I, Drake F, Zavarselk S, Tellis I, Hertzog P, Debouck C, Kola I. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 1999; 14: 1654-63.
8. Adami S, Supronik J, Hala T, Brown J, Garnero P, Haemmerle S, Ortmann CE, Bouisset F, Trechsel U. Effect of one year treatment with the cathepsin-K inhibitor, balicatib, on bone mineral density (BMD) in postmenopausal women with osteopenia/osteoporosis. ASBMR 2006, abstract 1085.
9. Stoch SA, Zajic S, Stone J, Miller DL, Van Dyck K, Gutierrez MJ, De Decker M, Liu L, Liu Q, Scott BB, Panebianco D, Jin B, Duong LT, Gottesdiener K, Wagner JA. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther 2009; 86: 175-82.
10. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, Dasilva C, Santora AC, Ince BA. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 2010; 25: 937-47.
11. Podgorski I. Future of anticathepsin K drugs: dual therapy for skeletal disease and atherosclerosis. Future Med Chem 2009; 1: 21-34.
12. Data on File. Inhibitory effect of ONO-5334 on human recombinant cathepsin K (E05QA012). Osaka: Ono Pharmaceutical Co., Ltd, 2005.
13. Data on File. Inhibitory effect of ONO-5334 on 6 cysteine proteases (E05QA025). Osaka: Ono Pharmaceutical Co., Ltd, 2005.
14. Data on File. An investigation of Ono's compound (ONO-5334) on 9 enzyme and 3 receptor binding assays (1056356). Osaka: Ono Pharmaceutical Co., Ltd, 2005.
15. Yamada H, Mori H, Nakanishi Y, Kunishige A, Nishikawa S, Tanaka M, Shiroya T. Orally active cathepsin K inhibitor, ONO-5334, potently improved bone mineral density not only in trabecular bone but also in cortical bone in ovariectomized Cynomolgus monkeys. A09002146, ASBMR 2009.
16. Data on File. Inhibitory effect of ONO-5334 on bone resorption after single administration in normal rats (E05QA022). Osaka: Ono Pharmaceutical Co., Ltd, 2005.
17. Cloos PAC, Fledelius C, Christgau S, Christiansen C, Engsig M, Delmas P, Body J-J, Garnero P. Investigation of bone disease using isomerized and racemized fragments of type I collagen. Calcif Tissue Int 2003; 72: 8-17.
18. Hoshino H, Takahashi M, Kushida K, Ohishi T, Inoue T. The relationship between the degree of β-isomerisation of type I collagen degradation products in the urine and ageing, menopause and osteoporosis with fractures. Osteoporos Int 1999; 9: 405-9.
19. Reginster JY, Henrotin Y, Christainsen C, Gamwell-Henriksen E, Bruyere O, Collette J, Christgau S. Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type 1. Calcif Tissue Int 2001; 69: 130-7.