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: Richard Eastell, Shinichi Nagase, Michiyo Ohyama, Maria Small, James Sawyer, Steven Boonen, Tim Spector, Tomohiro Kuwayama, Steve Deacon
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 26 Issue 6 Pg. 1303-12 (Jun 2011) ISSN: 1523-4681 [Electronic] United States
• PMID: 21312264 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Bone and Mineral Research.

Chemical References

• Biomarkers
• Enzyme Inhibitors
• ONO-5334
• Thiazolidines
• Cathepsin K

Topics

• Biomarkers (blood, urine)
• Bone Density (drug effects)
• Bone Remodeling (drug effects)
• Cathepsin K (antagonists & inhibitors)
• Demography
• Enzyme Inhibitors (adverse effects, pharmacology, therapeutic use)
• Female
• Humans
• Osteoporosis, Postmenopausal (blood, drug therapy, physiopathology, urine)
• Thiazolidines (adverse effects, pharmacology, therapeutic use)
• Treatment Outcome