The recent editorial concerning the disastrous Bial trial highlighted the design flaw of simultaneous (as opposed to sequential) dosing of a new cohort, but it did not address other critical issues important for a phase I trial 1.
To date, the only Bial regulatory document that has been released is the clinical protocol and that protocol is astoundingly bereft of basic information needed for the investigators and study staff to assess safety in a first in human trial. For example, there is no information on the anticipated half‐life of elimination in humans, nor is there any basic information concerning pharmacodynamic effects such as off‐rate, accumulation with repeated dosing and off‐target effects. Bial provides only summaries of AUC data, instead of C max and t 1/2. Their toxicology studies note that no toxicity was demonstrated, making them failed studies. What toxicity was observed? When did it occur? Was it life‐threatening or irreversible? If it occurs in humans, how should it be treated? And by the way, weren't there deaths in some of the toxicology studies? Weren't those considered adverse effects?
The longer Bial delays in releasing the treasure trove of toxicology reports (a total of nine Good Laboratory Practice (GLP) repeat dose studies), as well as their investigator's brochure and template informed consent, the worse their legal and financial liability will become.
Competing Interests
There are no competing interests to declare.
Nolop, K. (2016) Bial trial disaster. Br J Clin Pharmacol, 82: 561. doi: 10.1111/bcp.12956.
Reference
- 1. Eddleston M, Cohen AF, Webb DJ. Implications of the BIA‐102474‐101 study for review of first‐into‐human clinical trials. Br J Clin Pharmacol 2016; 81: 582–6. doi:10.1111/bcp.12920. [DOI] [PMC free article] [PubMed] [Google Scholar]