Gertsch Group

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland

Clinical Study Protocol N° BIA-102474-101

Clinical Study Protocol N° BIA-102474-101
Jurg Gertsch - Mon Jan 25, 2016 @ 04:18PM
Comments: 2

For the sake of transparency in the ongoing discussion about why it was possible that BIA-10-2474 (the in the protocol mentioned substance 3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide) went into phase O/1 clinical trials one needs to critically study and understand the study protocol approved by the ANSM, French Ministry of Health. Interestingly and worryingly, there is no mention of "covalent" or "mechanism-based" inhibition, despite of the fact that the compound does exactly that. The study protocols even mentions the term "reversible FAAH" inhibitor, which is rather misleading without the biochemical context of the measurements that led to this conclusion. There are of course covalent reversible inhibitors, but reversibility in the physiological context may be different from in vitro assays. Moreover, how was specificity assessed and how was the mecahnism based action discussed in the context of safety?

The study protocol raises many questions: The study conduct enables high flexibility for the trial (decision making committee). maybe at the expense of safety for the people involved in the trial. In the introduction there is no mention about mechanism of action, potential for side effects on about 200 protein targets with an idential enzyme mechanism as FAAH. Also, it is somewhat unclear how fast dosing could be escalated. The stopping rule for escalation to next level “drug related severe AEs of the same character in 4 or more subjects” was rather undefined and apparently there was no stopping rule for serious adverse events. 

I upload the study protocol that used to be confidential prior to the accident, but now in the public domain as it has been affecting people, researchers, drug developing companies and authorities. 

CLICK HERE TO DOWNLOAD STUDY PROTOCOL

Comments: 2

Comments

1. Phil Sanders   |   Wed Jan 27, 2016 @ 12:58AM

Thanks for communicating the protocol on your website

2. Xu Xing   |   Mon Feb 15, 2016 @ 07:07PM

No stopping rules for serious adverse events is a very unusual study protocol - Laboratoire Biotrial in Rennes will have to openly discuss their errors.

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