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Effects of teriparatide in Japanese and non-Japanese populations: bridging findings on pharmacokinetics and efficacy

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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.

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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.

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Authors and Affiliations

  1. Lilly Research Laboratories-Development Center of Excellence-Asia Pacific, Eli Lilly Japan K.K., Sannomiya Plaza Bldg., 7-1-5 Isogamidori, Chuo-ku, Kobe, 651-0086, Japan

    Mika Tsujimoto & Atsuko Iwata

  2. Lilly Research Laboratories-Development Center of Excellence-Japan, Eli Lilly Japan K.K., Kobe, Japan

    Kazunori Uenaka, Yoshihiro Higashiuchi & Hideaki Sowa

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  1. Mika Tsujimoto
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  2. Kazunori Uenaka
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  3. Atsuko Iwata
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  4. Yoshihiro Higashiuchi
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  5. Hideaki Sowa
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Correspondence to Mika Tsujimoto.

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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

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  • DOI: https://doi.org/10.1007/s00774-011-0314-4

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