The FUTURE Initiative
During the early development phases of some drugs, there have been phase I studies in genotyped volunteers to assess the impact of the genetic polymorphism on drug disposition. However, this is relatively uncommon, and usually is limited because of the small numbers studied, focus on the most well-known polymorphisms, and lack of assessment of combinations of polymorphisms. The major problem is the lack of an easily accessible, comprehensively genotyped, volunteer panel who can take part in phase I studies
To provide cohorts of fully genotyped individuals willing to partake in Phase I clinical trials/studies.
An important aspect which contributes to variability in drug response is the pharmacokinetics of the drug. This is usually due to variability in drug metabolising enzyme function and expression (which leads to variability in drug metabolism) or in drug transporter expression and function (which leads to variability in absorption, metabolism and excretion). The net effect of inter-individual variability in drug pharmacokinetics is variability in systemic drug exposure, leading to either under-exposure (and reduced efficacy) or over-exposure (and toxicity). In short, the dose administered does not necessarily equate drug exposure either systemically or at the site of action. Currently for most drugs, we ignore such pharmacokinetic variability, and in effect operate on the paradigm that “one dose fits all”.
The first panel will consist of healthy volunteers from a range of ethnicities, including at least 1000 individuals of Chinese origin.
The second panel will consist of patients with different degrees of hepatic and/or renal impairment. This cohort will be continually updated to ensure the panel is of adequate size to fulfil the needs of PK studies.
How it will work
All volunteers will be comprehensively genotyped for the full breadth of drug metabolising and transporter genes.
A “community” using a social media platform will be created to maintain a long-term relationship with the cohort so that they can be approached for recruitment to future studies irrespective of their geographical location.
Businesses and researchers will be able to submit proposals to identify relevant individuals in the cohorts that can be approached for involvement in Phase I trials/studies.