Denosumab Fracture Intervention Randomized Placebo Controlled Trial in Japanese Patients With Osteoporosis

Summary

Evaluate the efficacy and safety of denosumab in the treatment of involutional (postmenopausal and senile) osteoporotic subjects with prevalent fragility vertebral fracture(s)

Timeline

Start

2008-05

Primary completion

2012-06

Completion

2012-07

Outcome

Met primary endpoint

registry Denosumab vs Placebo; p = 0.0001; Hazard Ratio (HR) 0.343 (95% CI 0.194 to 0.606); Log Rank NCT00680953 ↗

paper Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months PMID 24646104 ↗

Publications

• Results Nakamura T, Matsumoto T, Sugimoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Shiraki M, Fukunaga M. Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014 Jul;99(7):2599-607. doi: 10.1210/jc.2013-4175. Epub 2014 Mar 19.
• Results Sugimoto T, Matsumoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Fukunaga M, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Okubo N, Shiraki M, Nakamura T. Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT). Osteoporos Int. 2015 Feb;26(2):765-74. doi: 10.1007/s00198-014-2964-2. Epub 2014 Nov 18.
• Okubo N, Matsui S, Matsumoto T, Sugimoto T, Hosoi T, Osakabe T, Watanabe K, Takami H, Shiraki M, Nakamura T. Relationship Between Bone Mineral Density and Risk of Vertebral Fractures with Denosumab Treatment in Japanese Postmenopausal Women and Men with Osteoporosis. Calcif Tissue Int. 2020 Dec;107(6):559-566. doi: 10.1007/s00223-020-00750-y. Epub 2020 Aug 25.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Alendronic Acid	Small molecule	35 mg	Oral
Subject	Denosumab	Monoclonal antibody	60 mg	Subcutaneous

Indications