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.

Abstract

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 2.5mg IR on awakening QD, or 25 or 37.5mg DR on awakening, following breakfast, or 30min after breakfast, QM for 12months. 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% (25mg DR following breakfast, n = 194), and 4.11% (37.5mg 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 30min 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 25mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5mg IR on awakening QD.