A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The oral calcitonin in postmenopausal osteoporosis (ORACAL) trial
A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The oral calcitonin in postmenopausal osteoporosis (ORACAL) trial
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DOI：
10.1002/jbmr.1602
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发表时间：
2012-08-01
影响因子：
6.2
通讯作者：
Krause, David S.
中科院分区：
文献类型：
--
作者：
Binkley, Neil;Bolognese, Michael;Krause, David S.
口服降钙素治疗绝经后骨质疏松症（ORACAL）研究是一项随机、双盲、双模拟、活性药物和安慰剂对照、多次给药、III期研究，旨在评估口服重组降钙素治疗绝经后骨质疏松症的疗效和安全性。共有565名年龄在46至86岁（平均66.5）的女性被随机（4：3：2）接受口服重组鲑鱼降钙素（rsCT）片剂（0.2？mg/d）加安慰剂鼻喷雾剂、合成鲑鱼降钙素（ssCT）鼻喷雾剂（200 IU/d）加安慰剂片剂、或安慰剂（安慰剂片剂加安慰剂鼻喷雾剂）分别治疗48周。所有妇女接受钙（=1000？mg/d）和维生素D（800 IU/d）。随机接受口服rsCT的女性腰椎骨密度（BMD）较基线增加的平均+/- SD百分比（1.5%+/- 3.2%）大于随机接受ssCT鼻喷剂（0.78%+/- 2.9%）或安慰剂（0.5%+/- 2.9%）的女性。3.2%）。接受鼻用降钙素治疗的患者腰椎BMD变化与安慰剂组无差异。口服rsCT治疗也比ssCT鼻喷雾剂更能改善转子和股骨近端总BMD。口服rsCT的骨吸收标志物的减少大于ssCT鼻喷雾剂或安慰剂接受者中观察到的减少。每个治疗组中约80%的受试者发生了不良事件，其中大多数的严重程度为轻度或中度。在所有治疗组中，近一半的女性报告了胃肠道系统不良事件，这是提前退出的主要原因。不到10%的女性经历了严重的不良事件，没有死亡发生。总体而言，口服rsCT在增加BMD和降低骨转换方面上级鼻用ssCT和安慰剂。口服rsCT与ssCT鼻喷雾剂或安慰剂一样安全且耐受性良好。口服降钙素可能为绝经后骨质疏松症妇女提供额外的治疗选择。(C)2012年美国骨与矿物质研究学会。
The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2?mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (=1000?mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean +/- SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5%+/- 3.2%) that was greater than those randomized to ssCT nasal spray (0.78%+/- 2.9%) or placebo (0.5%?+/- 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis. (C) 2012 American Society for Bone and Mineral Research.