hero image

This past January, a seemingly routine phase I clinical trial in France has turned into a nightmare.
At issue is a new drug, a fatty acid amide hydrolase (FAAH) inhibitor, BA-10-2474, from Portuguese company Bial. There are other FAAH inhibitors under study by other companies in the US and abroad but the issue here relates to the Bial drug.
A clinical research organization (CRO) Biotrials in Rennes, France began a phase I study in January. The protocol, in English, was published by the French newspaper Le Figaro. See also a summary as of 5-February.

This study involved 128 healthy volunteers studying the safety and PK/PD of the drug. There were 8 separate groups with each group comprising 6 volunteers to receive the drug and 2 placebo controls. Each received a single oral dose. Group one received 0.25 mg, with increases in each group to 1.25, 2.5, 5.0, 10, 20, 40 and 100 mg. Escalation was based on the safety in the previous group.

Based on various published reports in the press and on-line, there were no safety issues in the groups until the 40 mg group, Cohort 4, (some press reports say this was a 50 mg group though the protocol says 40 mg) was dosed. That is, there were no issues reported at each dose escalation until the 40/50 mg group was reached.

The 40/50 mg group (cohort 5) was dosed on January 5, nineteen days after the 20 mg group was dosed. On January 10, five days later, one volunteer was hospitalized with severe neurologic problems. On January 11, seven others also received the 40/50 mg dose. The hospitalized patient became comatose on January 11. Five of the newly dosed subjects were hospitalized between January 13 and 15. The French Health Agency was notified on January 14 of these serious adverse events. The first patient hospitalized died.  The other five are reported to be improving. The trial was stopped.

Several investigations were launched and the French Minister of Health commented at a Press Conference that the trial should have been stopped after the first person was hospitalized. She also noted that the lab should have warned the French Health Agency more quickly, though apparently they did not break any laws or regulations by notifying the agency 4 or 5 days after the events occurred. She also said the other participants in the trial should have been asked whether they wanted to continue.  The results of the French Ministry’s investigation were released (in French).

Others commented also:

All sorts of questions and issues are now being brought up and various investigations are still underway regarding this trial specifically and similar phase I trials in general. Such questions include:


Doubtless more details, charges, accusations, etc. will come over the next several weeks to months. Nonetheless, there are several things that can be learned even at this early stage of the situation in regard to both phase I studies, other studies and post-marketing safety.

Phase I Studies – Particularly in Volunteers

When trouble comes it will often come rapidly with no warning and with a need for immediate action – particularly if the subjects are normal volunteers.

So one act as though every SAE is possibly related and, if severe medically (and serious) it should be evaluated immediately and a decision made on whether to stop the study or make other changes.

Other Clinical Trials and Studies

Similar issues as seen in phase I but with some marked differences:

The Post-Marketing Situation

Terrible safety issues can occur at any time during the marketing of a drug. Sometimes the issues are related to the drug itself but there may be other issues not due to the drug or active moiety such as counterfeiting, tampering, medical errors etc.

What Should Sponsors, IND/NDA/MA Holders Do?

There should be no surprises here:


Related Articles