title: Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study.
abstract: Osteoporosis occurs when there is an imbalance between resorption and formation of bone, with resorption predominating. Inhibitors of cathepsin K may rebalance this condition. This is the first efficacy study of a new cathepsin K inhibitor, ONO-5334. The objective of the study was to investigate the efficacy and safety of ONO-5334 in postmenopausal osteoporosis. This was a 12-month, randomized, double-blind, placebo- and active-controlled parallel-group study conducted in 13 centers in 6 European countries. Subjects included 285 postmenopausal women aged 55 to 75 years with osteoporosis. Subjects were randomized into one of five treatment arms: placebo; 50 mg twice daily, 100 mg once daily, or 300 mg once daily of ONO-5334; or alendronate 70 mg once weekly. Lumbar spine, total hip, and femoral neck BMD values were obtained along with biochemical markers of bone turnover and standard safety assessments. All ONO-5334 doses and alendronate showed a significant increase in BMD for lumbar spine, total hip (except 100 mg once daily), and femoral neck BMD. There was little or no suppression of ONO-5334 on bone-formation markers compared with alendronate, although the suppressive effects on bone-resorption markers were similar. There were no clinically relevant safety concerns. With a significant increase in BMD, ONO-5334 also demonstrated a new mode of action as a potential agent for treating osteoporosis. Further clinical studies are warranted to investigate long-term efficacy as well as safety of ONO-5334.
authors.affiliation: University of Sheffield, Sheffield, United Kingdom. r.eastell@sheffield.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nagase
authors.forename: Michiyo
authors.initials: M
authors.lastname: Ohyama
authors.forename: Maria
authors.initials: M
authors.lastname: Small
authors.forename: James
authors.initials: J
authors.lastname: Sawyer
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Tim
authors.initials: T
authors.lastname: Spector
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kuwayama
authors.forename: Steve
authors.initials: S
authors.lastname: Deacon
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D003710:Demography; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D053778:Thiazolidines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C560865:ONO-5334; D053778:Thiazolidines; D056657:Cathepsin K