A man has died in France after participating in a clinical trial for a new painkiller developed by Portuguese pharmaceutical company BIAL. Following his admission to the Rennes University Hospital in Western France last week, a statement was released announcing his death on January 17th. A further five participants have been hospitalised, and despite being in a stable condition, French health authorities have warned that three of them may be affected by permanent brain damage.
The affected participants, all men aged 28 to 49, were taking part in a clinical trial conducted by private research company Biotrial on behalf of a separate company, BIAL. Each volunteer was paid €1900 (£1500) each in order to participate in the trial, which began on January 7th this year. Ninety of the 128 volunteers tested molecule that inhibits fatty acid enzymes, while the remaining participants received a placebo in place of the actual drug. Though neither the French authorities nor Biotrial has disclosed the identity of the molecule administered in the trials, it is believed to be a molecule referred to by the codename of BIA 10-2474.
The trial was the first to test the molecule on humans, measuring the effects of healthy people receiving the drug, which was aimed towards treating anxiety and motor disorders associated with Parkinson’s disease, and chronic pain in people with cancer, amongst various other conditions. Out of the 90 volunteers who received the actual drug, six were seriously or fatally affected, and the trial was immediately terminated as soon as severe reactions to the drug were reported. The remaining 84 volunteers have received no anomalies as a result of the trial, according to the Rennes University Hospital.
Though the incidents were publically acknowledged on January 15th, no official information has since been released, including the actual name and structure of the molecule used in the clinical trial. This has left both experts and the public in the dark as to the reason behind the failure of the trial, though BIAL claims they are “strongly committed” to discovering what went wrong.
Catherine Hill, a specialist in clinical-trial design and a former member of the scientific advisory board of France’s National Agency for Medicines and Health Products Safety (ANSM), believes that one possible reason behind this incident is the manner in which the trial was conducted. It is apparent that all six of the affected participants were given their doses on a simultaneous basis as opposed to sequential administration, which is the common practice of one participant receiving a test dose and being checked for serious effects before allowing the drug to be administered to others. According to Nature, simultaneous rather than sequential administration was identified as highly problematic following a tragic UK clinical trial in 2006 which saw multiple organ failure in six young men prior to their deaths. “Treating several individuals on the same day in a phase I trial was a big mistake,” says Hill.
Though the 2006 disaster in London has since changed the ways in which UK clinical trials operate, a French law was passed in 2012 intended to streamline the tight restrictions regarding research involving humans and to make France seem a more attractive place for companies such as BIAL to enact clinical trials. Sequential administration is known to be more efficient in terms of both costs and time, and many experts believe that the administration of high dosages of BIA 10-2474 in several patients may be the reason behind the death of a volunteer.
Bial spokeswoman Susana Vasconcelos says that the trial had been conducted “in accordance with all the good international practices guidelines, with the completion of tests and preclinical trials” and that the company “is committed to determine thoroughly and exhaustively the causes which are at the origin of this situation”. When asked to respond the media queries, the president and chief executive of Biotrial, Jean-Marc Gandon, stated that he cannot immediately answer because he is focused on trying to save the patients, and that his company will respond later.
Whatever the reason may be behind this disastrous trial, it is hoped that the death of a volunteer will lead to tighter laws regarding human experiments, and that a similar situation may be avoided in the future.