Module 5 Presentations

05/07/2024

France clinical trial - BIA 10-2474 (5)

Biotrial failed three major issues

1. The study should have been stopped when the first subject was hospitalized so the drug would not have been given to five others; 2. The incident should have been reported immediately, namely January 10, not four days later; 3. All other subjects should have been notified right away asking them if they would like to continue in the study.

The Royal Statistical Society was particularly critical, stating that it had "clear statistical reservations about the trial's study design", and that the protocol lacked features such as a risk assessment.

The Organisation for Professionals in Regulatory Affairs

BIA 10-2474

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France clinical trial - BIA 10-2474 (6)

The final report from the ANSM Committee appointed to investigate the matter concluded in April 2016 that:

• The most likely hypothesis to date is that of toxicity specific to the molecule via its binding to other brain cell structures, facilitated by its low specificity for its target enzyme;

• The use of multiple doses a lot higher than those leading (at least in humans) to complete and lasting FAAH inhibition, and; its probable gradual accumulation in the brain, undoubtedly related to the specific pharmacokinetic features of BIA 10 ‐ 2474.

The Organisation for Professionals in Regulatory Affairs

BIA 10-2474

44

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