Phase I Clinical Trial: One Death and Five Hospitalized in France

A person has died and 5 others have been hospitalized in France, after taking part in a clinical study for a new painkiller formulated by BIAL, a Portuguese pharmaceutical company.

Image credit: Biotrial.
Image credit: Biotrial.

The men were admitted to the Rennes University Hospital in western France on 11th Feb. One man was said to be brain-dead as a consequence of the investigational drug, and on 17th of Feb, the hospital released a statement stating his passing.

The other 5 men are believed to be in a stable conditon, though French health authorities have cautioned that 3 of them may be left with permanent brain damage.

French prosecutors say they have now extended their investigations into the clinical study to include possible manslaughter charges.

The phase 1 clinical study – performed by private research organization Biotrial – started on January 7th this year, registering 90 healthy people to analyze a new molecule known as a fatty-acid amide hydrolase (FAAH) enzyme inhibitor.

FAAH is an enzyme that can crack down endogenous cannabinoids (endocannabinoids) in the brain. Investigators have earlier recommended that preventing this enzyme could be an effective approach for treating chronic pain.

Is BIA 10-2474 the culprit?

French news website have presented a document – considered to have been offered by an individual who applied to be part of the study but who was rejected – that they say shows how this recent phase 1 clinical study was being performed.

The document declares that the FAAH inhibitor being examined was BIA 10-2474. While this drug is listed as being in phase 1 testing – which analyzes a drug’s safety – on BIAL’s Pipeline list, the pharmaceutical company, and Biotrial have not confirmed this to be true.

The document also suggests that 128 healthy subjects aged 18-55 took part in the study, 90 of whom were provided BIA 10-2474 at various doses, while the remaining individuals were given a placebo.

According to BIAL, the development of the FAAH enzyme inhibitor “has been performed since the beginning in obedience with all the good international practices recommendations, with the completion of tests and pre-clinical studies, especially in the area of toxicology.”

They add that the drug had currently been administered to 108 individuals “without any moderate or serious adverse reaction.”

While it is presently unclear what triggered the adverse reactions in 6 of the clinical trial subjects, BIAL states they are “highly committed” to figuring out and are working with all the appropriate authorities to do so.

“Our thoughts go out to the volunteers and their family members. We are working together with the Health agencies to know the cause of this accident,” added Biotrial in a statement.

The clinical study was terminated once reports emerged of severe reactions to the drug, and the other 84 volunteers were approached, 10 of whom underwent a medical examination, although Rennes University Hospital says no “anomalies” among these people have been recognized. An additional five trial individuals will undergo a medical examination.

Incident may increase questions about clinical trial processes

This is not the initial time an early-stage clinical study has lead to adverse outcomes. In 2006, a phase 1 clinical study performed in London, UK – dubbed the “Elephant Man trial” – lead to six young men being treated for multiple organ failure within hours of getting a drug known as TGN1412, developed to fight autoimmune disease and leukemia.

Manufactured by pharmaceutical organization TeGenero Immuno Therapeutics, the drug lead to one man losing his fingers and toes, while all men were informed they would probably develop cancers or autoimmune diseases in the long run because of their exposure to the drug.

It should be observed, however, that such severities in early-stage drug studies are rare, though this latest event is probably to increase questions about the safety of such studies and whether there should be more stringent procedural strategies in place.