Bridging analysis of the efficacy and safety of bazedoxifene in Japanese and global populations of postmenopausal women with osteoporosis.
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.
Saitama Center for Bone Research, Kubojima Clinic, 1785-2 Kubojima, Kumagaya, Saitama, 360-0831, Japan, itabashi@amail.plala.or.jp.
Akira
A
Itabashi
Kousei
K
Yoh
Arkadi A
AA
Chines
Takami
T
Miki
Masahiko
M
Takada
Hiroshi
H
Sato
Itsuo
I
Gorai
Toshitsugu
T
Sugimoto
Hideki
H
Mizunuma
Hiroshi
H
Ochi
Ginger D
GD
Constantine
Hiroaki
H
Ohta
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000737:chemistry; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D017102:Fracture Healing; D050723:Fractures, Bone / Q000209:etiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007564:Japan; D008055:Lipids / Q000737:chemistry; D008159:Lumbar Vertebrae / Q000187:drug effects*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D061214:Patient Safety; D017698:Postmenopause
D050071:Bone Density Conservation Agents; D007211:Indoles; D008055:Lipids; C447119:bazedoxifene