title: Effects of teriparatide in Japanese and non-Japanese populations: bridging findings on pharmacokinetics and efficacy.
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.
authors.affiliation: 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. Tsujimoto_mika@lilly.com
authors.forename: Mika
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uenaka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Iwata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Higashiuchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
mesh_terms: D000368:Aged; D044466:Asian People; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006262:Health; D006801:Humans; D007564:Japan; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D017698:Postmenopause / Q000187:drug effects; D012044:Regression Analysis; D019379:Teriparatide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide