Clinical Trials Protocol Design Of DPP-4 Inhibitors In The Treatmentof T2DM And The Problems Analysis Of T2DM Clinical Trials

Background and Objectives:Diabetes mellitus(DM)is widespread around the world, 95% are type 2 diabetes mellitus(T2DM), and C hina is the most.In all anti- hyperglycemia drug, dipeptide peptidase 4(DPP-4) inhibitor has developed rapidly and achieved great success among all the drugs of DM, the clinical trials of DPP 4 inhibitorswill enter a stage of vigorous development.The short period, the ambiguous end point and the simplistic inclusion and exclusion criteria of subjects from past literatures and the clinical trials of T2 DM registe red in Center of Drug Evaluation(CDE), are the danger to implementation of the trial and the drug production approval. This paper aim to analysis the clinical trials design of DPP-4 inhibitors, so that provide a reference for the relevant trials’ design.The quality of drug clinical trials, is directly related to the authenticity and accuracy of sub jects’ life, health and safety.Drug c linical trial is a continuous and complicated process, sorts of inevitable problems affect the quality.This paper summarize problems during clinical trial, then analysis the major reasons and put forward the reasonable suggestions and solutions, aim to provide a reference for improving the trials’ quality. Methods:Summarizing 88 randomized controlled trials(RC T) of DPP-4 inhibitors base on frequency statistics, analysis the principle of selection of subjects and endpoint.Summarizing AE reported in the literatures, analysis of AE in the clinical trials of DPP-4 inhibitors..For five Discovery the problems existed in the monitoring reports, auditing reports, table of random QC and query according to 5clinical trials of T2 DM, analysis of the problems mayprone to happenin the clinical trials of T2 DM.Results:Subjects: Inclusion Criteria in the age of 18(20)-80 y, diagnosed with T2 DM, the range of BMIbetween 20 to 40 or less than 40 and stable body weight in three months(the range less than 10%), Hb A1c(lower limit of 6.5%- 6.5%, up to 6.5%- 12%).The non- forbidden drugs must achieved stable dose, reasonable diet and exercise.Exclus ion criteria included in the Pancreas disease(surgery), DM complications, liver and kidney disfunction, serious cardiovascular disease, other serious diseases may affect thedrug’s effectand safety evaluation, the use of forbidden drugs and weight loss must be in Exclusion Criteria. Endpoints: Hb A1 c change compared with the baseline as the primary end point, secondary endpoint :the change of body weight, fasting plasma glucose(FPG) and the proportion of Hb A1 c of 6.5% or less(and/or 7.0%)are reasonable, the safety evaluation suit for every clinical trials include DPP-4 inhibitors. AE: Headache, upper respiratory tract infection, urinary tract infections, nasopharyngitis, backache, influenza, Hypoglycaemia, hypertension and gastrointestinal related AE(incidence of 4% or higher)prone to happen in DPP-4 inhibitors clinical trials. The problemsprone to happen in the clinical trials of T2DM: random QC inspection, inspection, and system found that the most common problem base on monitoring reports, auditing reports, table of random QC is the problems in study records /C RF, the most common problem is test value lack of judgment or judgment is wrong according to query. Conclusion:Summarize the design principles of clinical trials of DPP-4 inhibitors, then write a model protocol. Excellent monitors, scientific and reasonable monitor, the clinical research coordinator, use of electronic data capture system and the central randomization system can greatly reduce the problems in clinical trials of T2 DM, then improving the quality of trials.