A Framework Proposal to Follow‐Up on Preclinical Convulsive Signals of a New Molecular Entity in First‐in‐Human Studies Using Electroencephalographic Monitoring

Traditionally, in dose‐escalating first‐in‐human (FiH) studies, a dose cap with a 10‐fold safety margin to the no observed effect level in animals is implemented if convulsive events are observed in animals. However, the convulsive risk seen in animals does not generally translate to humans. Several lines of evidence are summarized indicating that in a dose‐escalating setting, electroencephalographic epileptiform abnormalities occur at lower...