Lessons from the fatal French study BIA-10-2474

In January the phase I study of the drug BIA-10-2474 conducted in Rennes, France, left one initially healthy volunteer dead and three with serious neurological damage, some of which may be permanent.1 2

This was a not unusual phase 1 study of a new wannabe drug and included four substudies: single ascending doses, multiple ascending doses, a food interaction study, and some pharmacodynamic testing looking for potential indications. Dose escalation was based on pharmacokinetic data from animal studies and from the previous series in this phase I study.

The study of single ascending doses took place uneventfully up to the maximum dose of 100 mg. The first four series of multiple ascending doses had no problem up to 20 mg for 10 days. Suddenly, on the fifth day of the fifth series (50 mg daily) one participant developed neurological problems and was admitted to hospital. The next day the other participants received their treatment. Three of the four remaining participants had neurological symptoms …