Phase II/III, randomized, double-blind, parallel-group study of monthly delayed-release versus daily immediate-release risedronate tablets in Japanese patients with involutional osteoporosis
Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L2–L4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L2–L4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L2–L4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5–4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.
KeywordsOsteoporosis Risedronate Delayed release Immediate release Japan
This study was supported by the Joint Development Program of EA Pharma Co., Ltd., and Takeda Pharmaceutical Company Ltd. The authors thank all the patients who participated in these studies and their families, as well as the investigators and site staff who made these studies possible. Writing support was provided by Matthew Hallam and Stephen Hill of FireKite, an Ashfield company, part of UDG Healthcare plc, during the development of this manuscript, which was funded by Takeda Pharmaceutical Company Ltd., in compliance with Good Publication Practice 3 ethical guidelines (Battisti et al., Ann Intern Med 2015;163:461–4). This trial was funded by EA Pharma Co., Ltd. (Tokyo, Japan), and Takeda Pharmaceutical Company Limited (Osaka, Japan). JapicCTI-142439 (registered by EA Pharma); JapicCTI-142440 (registered by Takeda).
Compliance with ethical standards
Conflict of interest
S.S. has received grants/research support from Daiichi-Sankyo, Eisai, and Takeda; and is a member of speaker’s bureaus for Asahi Kasei, Astellas Pharma, Chugai, Daiichi-Sankyo, Eisai, Merck Sharp & Dohme, Ono, Pfizer, Takeda, and Teijin Pharma. H.K. has received consulting fees from Asahi Kasei Pharma, Daiichi-Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan. H.H. has received grants/research support or lecture fees from Asahi Kasei Pharma, Astellas Pharma, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Mitsubishi Tanabe, Merck Sharp & Dohme, Ono, Pfizer, Taisho Toyama Pharmaceutical, Takeda, and Teijin Pharma. T.So. has received research grants from Asahi Kasei Pharma, Astellas Pharma, Daiichi-Sankyo, Pfizer, Taisho Toyama Pharmaceutical, Takeda, and Teijin Pharma; and has received consulting fees from Daiichi-Sankyo and Takeda. H.O. is an employee of EA Pharma. T.F. and E.S. are employees of Takeda Pharmaceutical. S.T. has been a consultant and received honoraria from Eisai, given expert testimony for Takeda Pharmaceutical and EA Pharma, undertaken contracted research for EA Pharma, and received endowments from Takeda Pharmaceutical. T.Su. has received research grants from Astellas Pharma, Eisai, Daiichi-Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan as well as consulting and/or lecture fees from Asahi Kasei Pharma and Daiichi-Sankyo.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided written, informed consent. Trial registration: ClinicalTrials.gov number NCT02063854.
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