Itabashi Akira, Yoh Kousei, Chines Arkadi A, Miki Takami, Takada Masahiko, Sato Hiroshi, Gorai Itsuo, Sugimoto Toshitsugu, Mizunuma Hideki, Ochi Hiroshi, Constantine Ginger D, Ohta Hiroaki
Saitama Center for Bone Research, Kubojima Clinic, 1785-2 Kubojima, Kumagaya, Saitama, 360-0831, Japan,
J Bone Miner Metab. 2015 Jan;33(1):61-72. doi: 10.1007/s00774-013-0554-6. Epub 2014 Apr 9.
This study examined whether the global clinical data for bazedoxifene could be extrapolated to a Japanese population by evaluating the results of a phase 2 study in postmenopausal Japanese women with osteoporosis as compared to those of a pivotal, phase 3 study. The efficacy of bazedoxifene 20 and 40 mg versus placebo on lumbar spine bone mineral density (BMD), bone turnover markers, lipid profile, incidence of fractures, and safety parameters was compared between the Japanese phase 2 study (N = 429) and the global phase 3 study (N = 7,492) during a 2-year period. In the primary population for assessment of bridging, differences in the mean percent change from baseline in lumbar spine BMD at 2 years relative to placebo were greater for women treated with bazedoxifene 20 and 40 mg in the phase 2 study than in the phase 3 study. BMD changes in the bazedoxifene groups were confirmed to be similar between the phase 2 study population and a subset of the phase 3 study population with similar baseline characteristics. The effects of bazedoxifene on incidence of fractures, bone turnover markers, and lipid metabolism were similar between studies. There were no major differences in safety parameters between studies. The greater improvement in lumbar spine BMD and similar results in bone turnover markers, fracture incidence, and safety profile observed with bazedoxifene in the phase 2 study compared with the phase 3 study confirmed the feasibility of extrapolating the global clinical data to a Japanese population.
本研究通过评估一项针对日本绝经后骨质疏松症女性的2期研究结果,并与一项关键的3期研究结果进行比较,来检验巴多昔芬的全球临床数据是否可外推至日本人群。在为期2年的时间里,比较了日本2期研究(N = 429)和全球3期研究(N = 7492)中,20毫克和40毫克巴多昔芬与安慰剂相比,在腰椎骨矿物质密度(BMD)、骨转换标志物、血脂谱、骨折发生率和安全性参数方面的疗效。在用于评估桥接的主要人群中,2期研究中接受20毫克和40毫克巴多昔芬治疗的女性,相对于安慰剂,2年时腰椎BMD自基线的平均变化百分比差异,比3期研究中的更大。2期研究人群与3期研究中具有相似基线特征的一个亚组之间,巴多昔芬组的BMD变化被证实是相似的。两项研究中巴多昔芬对骨折发生率、骨转换标志物和脂质代谢的影响相似。两项研究在安全性参数方面没有重大差异。与3期研究相比,2期研究中巴多昔芬在腰椎BMD方面有更大改善,在骨转换标志物、骨折发生率和安全性方面有相似结果,这证实了将全球临床数据外推至日本人群的可行性。