Department of Orthopedic Surgery and Rheumatology, Kindai University Nara Hospital, 1248-1 Otodacho, Ikoma, Nara, 630-0293, Japan.
Department of Orthopedic Surgery, Nojima Hospital, Tottori, Japan.
J Bone Miner Metab. 2020 Jan;38(1):86-98. doi: 10.1007/s00774-019-01031-x. Epub 2019 Aug 16.
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 (L-L) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L-L) 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 (L-L) 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.
口服即释（IR）利塞膦酸钠片的吸收会因食物摄入而减少，因此开发了一种缓释（DR）片剂，以克服在空腹条件下服用 IR 片剂的必要性。这项随机、双盲、II/III 期研究比较了日本绝经后骨质疏松症患者每日一次口服（QD）利塞膦酸钠 IR 和每月一次（QM）DR 片剂的疗效和安全性。患者接受 2.5mg IR 在早晨觉醒时 QD，或在早餐后或早餐后 30 分钟时接受 25 或 37.5mg DR QM，持续 12 个月。主要终点是在早晨觉醒时接受利塞膦酸钠 IR 和早餐后接受 DR 的患者从基线到研究结束（第 12 个月，最后观察到的向前结转[M12，LOCF]）的平均腰椎（L-L）骨密度（BMD）平均百分比变化的非劣效性。在 M12，LOCF 时（L-L）BMD 的平均百分比变化分别为 5.07%（IR 在觉醒时，n=190）、3.36%（25mg DR 早餐后，n=194）和 4.11%（37.5mg DR 早餐后，n=181）。在早餐后接受 DR 的组中，（L-L）BMD 的平均百分比变化与各自的早晨觉醒和早餐后 30 分钟接受 DR 的组相比数值较低。各组之间治疗中出现的不良事件（TEAE）的总发生率相当。在 DR 组中，1.5-4.0%的患者报告了可能与急性期反应相关的 TEAEs，而 IR 组中为 0%。在这项研究中，对于早餐后 QM 的 37.5 或 25mg DR（p=0.1346 或 p=0.6711）与早晨觉醒时 QD 的 2.5mg IR 相比，非劣效性无法宣布。
