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

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

A Randomized, Double-Blind, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of Denosumab in Japanese Osteoporotic Subjects With Prevalent Fragility Vertebral Fracture(s)

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

Denosumab (subcutaneously - every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months).

Placebo (subcutaneously every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months).

Alendronate sodium hydrate oral tablets weekly + daily calcium and vitamin D supplements for 24 months (open label reference arm).

Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).

Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).

Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo

The results are expressed as percentage by Kaplan-Meier estimate the percentage of participants with non-vertebral fractures

Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo.

Inclusion Criteria: Involutional (postmenopausal and senile) osteoporosis with prevalent fragility vertebral fractures Exclusion Criteria: Any underlying condition,(other than BMD) that might have resulted in abnormal bone metabolism

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.

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.