Report: High Doses of Experimental Drug Caused Brain Damage in Botched French Trial

Some subjects received doses 10 to 40 times higher than necessary

An investigation into a clinical test in France that left one person dead and put five others in a hospital has found evidence of brain damage in people who took high doses of the experimental pain medicine, according to a report from NPR News.

The early-stage clinical study was shut down in January when the adverse effects surfaced. It was the first time the drug, BIA 10-2474, had been tested in human subjects. BIA 10‐2474 is a reversible inhibitor of fatty acid amide hydrolase (FAAH), one of the main mediators of the endocannabinoid system. It was developed by a Portuguese pharmaceutical company, Bial.

A recent report from a French scientific committee concluded that subjects who received high cumulative doses of the drug sustained damage to their brains, specifically the hippocampus and pons. Those who received lower doses showed no consistent adverse effects.

A total of 90 people took the experimental drug. The six who were hospitalized had gotten the highest dose, which was 10 to 40 times higher than that needed to completely block the FAAH enzyme. All six patients received a cumulative dose higher than 250 mg, and all six experienced “serious” central nervous system symptoms, the committee noted.

The panel has asked Bial to explain why the company conducted preliminary studies in four species of animals, as opposed to the usual two; why it decided to continue studies of the potential pain reliever when it worked in only two animal tests; and why it chose to test such high cumulative doses in people.

The FDA is also looking into the case. The agency said in late January that while BIA 10-2474 hasn’t been tested in the U.S., studies are being conducted on other drugs that work the same way.

Sources: NPR News; March 10, 2016; and TSSC Meeting Minutes; March 7, 2016.