Abstract
Teriparatide is an anabolic therapy for osteoporosis approved in the United States since 2002 and European Union since 2003; however, approval in Japan lagged significantly. This report describes analyses based on International Conference on Harmonisation (ICH) E-5 guidelines that support bridging between Japanese studies and the large Fracture Prevention Trial (FPT). We analyzed data from single teriparatide doses in healthy Japanese and Caucasian postmenopausal women (J-PK) and from studies of 6 months [Phase 2, dose ranging (J-Ph2)] and 12 months [Phase 3, efficacy and safety (J-Ph3)] of randomized, placebo-controlled, once-daily treatment in Japanese subjects with osteoporosis. In J-PK, apparent teriparatide area-under-the-curve (AUC) and peak concentration (C max) were up to 40% higher in Japanese versus Caucasian women; however, body weight-adjusted values were comparable between populations; these findings were supported by population pharmacokinetic analyses. Between the FPT and Japanese studies, baseline demographic characteristics were similar but bone mineral density (BMD) at lumbar spine (L1–L4) and body weight were lower for Japanese subjects. With teriparatide 20 μg/day, significant increases in BMD were observed compared to placebo at 12 months in both the FPT and J-Ph3 study, and percent change and actual change in BMD were comparable between studies. Dose response at 6 months was also comparable across populations. No novel safety signals were identified in Japanese subjects. These analyses show that teriparatide clinical data met ICH E-5 criteria for bridging. Findings from foreign trials such as the FPT can thus be extrapolated to Japanese subjects treated with teriparatide 20 μg/day.
Similar content being viewed by others
References
Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM et al (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970
Chen P, Miller PD, Recker R, Resch H, Rana A, Pavo I et al (2007) Increases in BMD correlate with improvements in bone microarchitecture with teriparatide treatment in postmenopausal women with osteoporosis. J Bone Miner Res 22:1173–1180
Dobnig H, Sipos A, Jiang Y, Fahrleitner-Pammer A, Ste-Marie LG, Gallagher JC et al (2005) Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab 90:3970–3977
Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA (2007) Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis. J Bone Miner Res 22:149–157
Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB (2007) Effects of a one-month treatment with PTH(1–34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res 22:495–502
McClung MR, San MJ, Miller PD, Civitelli R, Bandeira F, Omizo M et al (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441
Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S et al (2008) Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 23:1591–1600
Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A et al (2003) The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18:9–17
Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA et al (2007) Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis. N Engl J Med 357:2028–2039
Hirai Y, Kinoshita H, Kusama M, Yasuda K, Sugiyama Y, Ono S (2010) Delays in new drug applications in Japan and industrial R&D strategies. Clin Pharmacol Ther 87:212–218
(1998) Ethnic factors in the acceptability of foreign clinical data E5 (R1). International Conference on Harmonisation website. Accessed 23 June 2010 (updated)
Uyama Y, Shibata T, Nagai N, Hanaoka H, Toyoshima S, Mori K (2005) Successful bridging strategy based on ICH E5 guideline for drugs approved in Japan. Clin Pharmacol Ther 78:102–113
Delmas PD, Calvo G, Boers M, Abadie E, Avouac B, Kahan A et al (2002) The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis. Osteoporos Int 13:1–5
Reginster JY, Abadie E, Delmas P, Rizzoli R, Dere W, der AP et al (2006) Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men. Osteoporos Int 17:1–7
Boonen S, Marin F, Mellstrom D, Xie L, Desaiah D, Krege JH et al (2006) Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective. J Am Geriatr Soc 54:782–789
Miyauchi A, Matsumoto T, Shigeta H, Tsujimoto M, Thiebaud D, Nakamura T (2008) Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study. J Bone Miner Metab 26:624–634
Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502
Orimo H, Sugioka Y, Fukunaga M, Muto Y, Hotokebuchi T, Gorai I et al (1998) Diagnostic criteria of primary osteoporosis. J Bone Miner Metab 16:139–150
Chen P, Miller PD, Delmas PD, Misurski DA, Krege JH (2006) Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21:1785–1790
Uusi-Rasi K, Semanick LM, Zanchetta JR, Bogado CE, Eriksen EF, Sato M et al (2005) Effects of teriparatide [rhPTH (1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36:948–958
Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF (2003) Recombinant human parathyroid hormone (1–34) (teriparatide) improves both cortical and cancellous bone structure. J Bone Miner Res 18:1932–1941
Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K et al (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355
Iki M, Kagamimori S, Kagawa Y, Matsuzaki T, Yoneshima H, Marumo F (2001) Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study. Osteoporos Int 12:529–537
Recker RR, Marin F, Ish-Shalom S, Moricke R, Hawkins F, Kapetanos G et al (2009) Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 24:1358–1368
Acknowledgments
The studies described in this work were funded by Eli Lilly and Company. The authors would like to thank Thomas Melby of i3 Statprobe and Miho Hatano of Eli Lilly Japan K. K. for assistance in the preparation of the manuscript.
Conflict of interest
All authors are employees of Eli Lilly Japan, K.K.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Tsujimoto, M., Uenaka, K., Iwata, A. et al. Effects of teriparatide in Japanese and non-Japanese populations: bridging findings on pharmacokinetics and efficacy. J Bone Miner Metab 30, 326–337 (2012). https://doi.org/10.1007/s00774-011-0314-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00774-011-0314-4