food effect

Testing the bioavailability of drugs in fed & fasted states

First-in-human trials of oral IMP are usually done with subjects in the fasted state. That’s partly because it’s safer to take medicines on an empty stomach, but it’s also because prior feeding may have profound effects – sometimes reducing bioavailability, and sometimes increasing it.

It’s simple and convenient for subjects to fast in single-dose trials, but things get more complicated in repeated-dose trials: it’s burdensome for subjects to fast before every morning dose.  What’s more, it’s sometimes essential to dose subjects more than once daily, yet it’s impossible to achieve a true fasting state every day before the evening doses.

For all those reasons, we try to incorporate in our FIH trials an assessment of the effect of prior feeding on the pharmacokinetics of the IMP. We scrupulously follow the FDA guideline on the size and constituents of a standard, high-fat breakfast. Our on-site kitchens have long experience of preparing accurately calibrated meals, and our Ward teams have unequalled experience of obtaining top-quality pharmacokinetic data. As soon as we know the effect of prior feeding on the bioavailability of the IMP, we can design an appropriate protocol for the repeat-dose trial.

At any stage in the development of an IMP, the sponsor may develop a new formulation with the aim of improving its pharmacokinetic properties. Each new formulation requires a bioavailability trial that includes an assessment of the effect of prior feeding. We’re happy to advise on the design of such studies, or to execute a trial to the sponsor’s specification.