Current Status of Global Clinical Trials and Studies on Population Differences within East Asians for Promotion of East-Asian Clinical Trials

Abstract

Primary strategy for conducting clinical trials in Japan has been shifting from domestic trials to bridging, and then global clinical trials. While several domestic guidelines have been released in recent years to assist in initiating global clinical trials, this issue was adopted as an ICH topic (E17) in 2014, and a draft of guideline was released to the public in 2016 for public consultation. Although multi-regional clinical trials including Japan, EU and US are common, East-Asian clinical trials have been also performed since East-Asian populations are assumed to have very similar genetic and cultural backgrounds. However, possibility is not excluded that population differences in pharmacokinetics and drug responsiveness may exist even among East-Asians. As a part of agenda for Japan-Korea-China Director-General Meeting on Pharmaceutical Affairs, Japan has been heading studies on differences in pharmacokinetic and drug responsiveness among East-Asian populations. Pharmacokinetic studies of three drugs on Japanese, Korean, Han Chinese, and Caucasian populations revealed no differences when the subjects in each population were stratified by genetic polymorphisms and extrinsic factors such as food and drinking water were normalized. These results suggest the importance of genetic polymorphisms and extrinsic factors in planning pharmacokinetic studies. Besides, we compared allele frequencies of more than 50 functional genetic polymorphisms in East-Asian populations, and found that generally, large differences were not observed in drug metabolizing enzymes and transporters; however, frequency differences were seen in HLA alleles associated with severe adverse drug reactions. We hope that our post and future results will promote East-Asian clinical trials, which will accelerate the availability of new drugs in these populations.