Safe Dosing for Organ Impairment

A model-enhanced view into exposure levels supported high-confidence dose selection and opened the way for study in patients with organ impairment.

A small virtual pharmaceutical company achieved clinical proof-of-concept for a new formulation of an approved drug, which it hoped would overcome a contraindication to use the drug in a key patient population.

In early-phase trials, the drug candidate showed promise to fill an unmet need by making the oral treatment safe for patients with organ impairment, a contraindication for the approved formulation. Due to its limited absorption into the bloodstream, the new drug was expected to reach therapeutic concentrations at its target in the GI tract while avoiding high systemic exposures in patients with reduced drug clearance.

In order to move ahead with large-scale trials, the drug sponsor sought a stronger understanding of the dose-exposure relationship. In particular, they needed compelling evidence that they would achieve safe exposures in patients with organ impairment to convince regulators to remove a partial clinical hold in that population.