Clinical trial disaster

A Phase 1 clinical trial has gone seriously awry, with one volunteer now dead and others with serious, possibly irreversible, neurological damage.

The clinical trial, run by French company Biotrial, was focusing on BIA 10-2474 — a pharmaceutical compound developed by Portuguese company Bial. The molecule under test is an inhibitor of fatty acid amide hydrolase (FAAH). This enzyme normally degrades and terminates the action of our naturally occurring biochemicals, including ananadamide. By prolonging the action of ananadamide, FAAH inhibitors have the potential to reduce pain and anxiety, among other neurological conditions.

The clinical trial was approved in June last year. Since July, at least 90 volunteers have completed the trial without any adverse events being recorded. The volunteers were all men aged 28 to 49. Another 38 were given a placebo, which is fairly unusual in Phase 1 trials as they essentially look at the safety, tolerance and pharmacological profile of the molecule. Dosages typically start at very low levels while safety is established. However, there are always risks inherent in first-in-human testing and, regardless of the extent of prior animal studies, not all risks can be predicted.

Even so, serious adverse events on Phase 1 trials are very rare. A meta-analysis of non-cancer Phase 1 drug trials, published in The BMJ last year, found there had been no deaths and serious adverse events in only 0.31% of participants.

In the Bial/Biotrial trial, the same dose of the drug was administered orally to a group of six men on 7 January. On 10 January, one of the participants started to show signs that something had gone wrong, and he was taken to hospital in a serious condition. The five other volunteers in the group were also taken to hospital at different stages at the beginning of the week.

The trial was halted on 11 January.

The volunteer who was first admitted to hospital, and who has subsequently died, was initially described as being ‘clinically dead’, or brain-dead, after being assessed by doctors.

Four of the others show signs of neurological trouble, with doctors saying three of them are suffering from ‘handicaps’ that are potentially irreversible.

The final patient in hospital has not shown any of the symptoms but is being monitored, given what happened to the others taking part in the trial.

All of those who took the drug will be given an MRI scan to determine whether they have suffered any adverse effects.

What went wrong will undoubtedly be investigated in depth by all of the companies involved, as well as all of the regulatory authorities, in an attempt to ensure that more healthy volunteers do not die in clinical trials.