Microdosing results prove to be CREAM of the crop
The long-awaited results from the Consortium for Resourcing and Evaluating AMS Microdosing (CREAM) trial have been released.
The long-awaited results from the Consortium for Resourcing and Evaluating AMS Microdosing (CREAM) trial have been released.
The trial was designed to determine if human pharmacokinetic data, obtained after a sub-pharmacological microdose of drug, allows acceptable prediction of pharmacokinetics at pharmacological dose levels, with the aim of facilitating drug candidate selection for subsequent human development.
Having reviewed the trial data, the CREAM sponsors said: 'Microdosing is a valuable tool in drug development, with three of the five selected drugs resulting in predictive human pharmacokinetic data, which will allow the right decision to be made for further drug development. Two of the drugs deviated from linear pharmacokinetic behaviour, but nevertheless the microdose results gave useful insights into the properties of the drugs. Given the fact that the compounds were selected because of their difficult pharmacokinetic properties, we consider the outcome of the trial to be a success.'
The trial was instigated by the UK-based specialist CRO and accelerator mass spectrometer experts Xceleron and Dutch Phase I/IIa clinical CRO Pharma BioResearch, alongside four international industry sponsors (F Hoffmann-La Roche - Switzerland; Eli Lilly and Company - US; Servier Laboratories - France, and Schering - Germany), in response to an EMEA position paper that, frowning upon the paucity of data to support the concept, encouraged the pharmaceutical industry to adopt microdosing.
The trial - set up to be a rigorous test using compounds that were expected to strongly challenge the microdosing concept - entailed the selection of five drug compounds with known and different pharmacokinetic characteristics, considered representative of the types of issues that arise in preclinical development that may make prediction of human pharmacokinetics problematic. Each of the compounds was administered at a microdose level and at a therapeutic dose level to subjects in an appropriate crossover design.