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

J Bone Miner Metab. 2012 May;30(3):326-37. doi: 10.1007/s00774-011-0314-4. Epub 2011 Sep 21.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacokinetics
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use
  • Demography
  • Dose-Response Relationship, Drug
  • Female
  • Health
  • Humans
  • Japan
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / physiopathology
  • Male
  • Models, Biological
  • Osteoporosis / drug therapy
  • Osteoporosis / physiopathology
  • Postmenopause / drug effects
  • Regression Analysis
  • Teriparatide / adverse effects
  • Teriparatide / pharmacokinetics*
  • Teriparatide / pharmacology
  • Teriparatide / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • White People*

Substances

  • Bone Density Conservation Agents
  • Teriparatide