FDA Investigates Clinical Trial After Drug Leaves 1 Dead, 4 Seriously Injured

Fatalities in phase 1 trials conducted in the U.S. are extremely rare.
Fatalities in phase 1 trials conducted in the U.S. are extremely rare.

A European phase 1 clinical study of a fatty acid amide hydrolase (FAAH) inhibitor has resulted in the death of one enrolled participant and neurological injury for four others. The trial, which was conducted by the French research organization, Biotrial, concentrated on BIA 10-2474; an investigational new drug (IND) manufactured by Portuguese company Bial.

One hundred and twenty-eight healthy subjects were recruited for the trial with 90 people receiving different doses of the drug. No serious adverse effects were seen when subjects were given escalating single doses, however the subjects who became ill were those first to receive the multiple-dose regimen over the course of several days. The simultaneous administration of high doses to several subjects, rather than sequential administration (one subject receiving the dose and being observed before others receive it) is one possible safety issue to note. In 2006, multiple patients in a clinical trial in London suffered organ failure due to simultaneous drug administration of a monoclonal antibody being developed for leukemia and rheumatoid arthritis.

In response to the fatal outcome of the trial, the US Food and Drug Administration (FDA) has begun a review of the safety information for FAAH inhibitors currently under investigation in the U.S. FDA officials are working with European regulators to learn as much as possible about the recent tragic trial, including the European Medicines Agency (EMA) and the French national medicines agency (ASNM).

BIA 10-2474 is reported to be an inhibitor of FAAH, an enzyme involved in cell function in the nervous system. Previous studies centering on FAAH inhibitors have investigated their potential therapeutic use in a number of neurological disorders. The recent study in France is the first human fatality following exposure to an FAAH inhibitor. 

Fatalities in phase 1 trials conducted in the U.S. are extremely rare. Before any human volunteers can be enrolled in a phase 1 study in the U.S., sponsors must submit rigorous laboratory and animal data to the FDA in an IND application. A 30-day waiting period after IND submission allows the FDA to review safety data and determine if the it is reasonably safe to proceed testing in human volunteers.

For more information visit FDA.gov