Phase I trial links fatty acid amide hydrolase inhibitor to severe neurologic disorder
medwireNews: Researchers warn of neurologic adverse effects with BIA 10-2474, a reversible fatty acid amide hydrolase inhibitor with analgesic and anti-inflammatory potential.
When given to healthy volunteers in single doses of 0.25 to 100 mg and repeated oral doses of 2.5 to 20 mg for 10 days as part of a phase I safety study there were no serious adverse events, but among six individuals given 50 mg/day, adverse neurologic effects developed in five.
The details for four of these patients, reported in The New England Journal of Medicine, describe an acute and rapidly progressive neurologic syndrome in three of the patients that developed after 5 days of treatment.
The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging (MRI) showed bilateral and symmetric cerebral lesions involving predominantly the pons and hippocampi.
Partial reversal of the syndrome was achieved in two of these individuals, although one had residual memory impairment and one had residual cerebellar syndrome. The remaining patient became brain dead.
The fourth study participant developed an asymptomatic cavernous malformation in the brain stem, but had normal MRI scans and remained asymptomatic.
Gilles Edan (Rennes University Hospital, France) and co-researchers say their findings suggest “direct toxicity of BIA 10-2474,” but add that “the precise mechanism of this toxic cerebral syndrome is unknown.”
By Lucy Piper
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016