The possibility of performing complete simulations of clinical trials, based on pharmacological action models, has been considered since the advent of the computer era, as a tool to optimise their practical realisation. Thanks to the advances in computation technology and in discrete event simulation tools, today it is possible to perform realistic, large-scale clinical trial simulations in a regular basis using suitable simulation tools. OBJECTIVES: We illustrate the process of use the realistic simulator LeanSim, previously for the concrete case of pilot clinical trials devoted to testing efficacy of the antiretroviral didanosine in a group of 50 patients with virologic failure presenting different mutations in the gen of HIV reverse transcriptase. It can origin resistance to transcriptase inhibitors and it can affects the efficacy of treatment designed to reduce the viral load in AIDS patients. METHODS: LeamSim is basically a discrete simulation tool developed in C/C++ that can be applied in any ambit, but accepts personalised elements construction, in order to adapt the simulation model to the reality that want to be simulated (this is the lean simulation metaphor). Other important LeanSim aspect is the way in with the model is constructed, this is, via the process definition, which is closer to the clinical trials experiment definition. RESULTS: LeanSim allow the population variability simulation (inter/intra patients) and its low cost let general use extend during optimisation previously the clinical trial starts. CONCLUSIONS: A simulation model based in Linear Mixed Models was estimated and during the simulation various scenarios were simulated to optimise sample size, effect of missing values, number of centres recruiting patients and the variability inter/intra patients and the previous results indicate the advantages of use this new tool.