Clinical development standard in Japan has changed over the last decades along with ICH E5 and Japan guidelines (JP GLs; by MHLW, PMDA) that support use of non-Japanese data as part of clinidacal data package for NDA in Japan, which is practically implemented as "bridging study" or "global study". After ICH-E51 and JP GLs for multi regional clinical trial2-3, timeline to develop drugs in Japan had also been synchronized with Western countries and we no more hear the word "drug lag" in Japan. In current Japan standard development, participation to international phase 3 clinical trials is encouraged, which avoids repeating stand-alone trials in Japanese patients that are often underpowered. In recent JP GL4 referring to phase I and multi regional clinical trial, J-Ph1 studies are stated as not necessarily required prior to Japan's participation to global studies ifforeign clinical data ensure safety in Japanese patient population. In order to optimize development scenario in Japan, not only to take advantage of recent regulation in Japan, inter-ethnicity comparison for PK and safety (and efficacy) is increasingly important both in early and late phase of clinical studies. For example, PMDA is often concerned about the consistency of outcomes in the subset of Japanese patients and the total trial population.
Body size is ruitinely considered, and in most cases account for signifincant part of PK difference between Japanes and non-Japanese patient population. However, it is not always sufficient factor to explain the inter-ethnicity difference depending on drug's characters.
We would like to present overview of body size effects based on our experiences in drug development and to discuss how pharmacometric appproach can support our development.
1. ICH E5: Ethnic factors in the acceptability of foreign clinical data 1998
2. JP GL: Basic principles on global clinical trials 2007
3. JP GL: Basic principles on global clinical trials (reference cases) 2012
4. JP GL: Basic principles for conducting phase I trials in the Japanese population prior to global clinical trials 2014