Japan-based Otsuka Pharmaceutical and Danish firm Lundbeck have started patient enrolment in two Phase III clinical trials of brexpiprazole to treat manic episodes in patients with bipolar I disorder.
While the mechanism of action is unknown, brexpiprazole’s efficacy is thought to be mediated with partial agonist activity at serotonin 5-HT1A and dopamine D2, and antagonist activity at serotonin 5-HT2A receptors.
Additionally, brexpiprazole is said to have high affinity for noradrenaline alpha1B/2C receptors.
The multi-centre, randomised, double-blind Phase III trials will investigate the safety, efficacy and tolerability of brexpiprazole in patients having an acute manic episode, with or without mixed features, requiring hospitalisation.
The trial’s primary endpoint is mean change from baseline to day 21 in the Young-Mania Rating Scale (YMRS) total score, while the key secondary endpoint is similar change in Clinical Global Impression – Bipolar (CGI BP) severity-of-illness score in mania during the double-blind treatment period.
YMRS score is a clinician rating scale used to evaluate mania symptoms based on subjective reports and clinical observations of a patient’s condition.
Otsuka discovered the investigational candidate and is developing it in alliance with Lundbeck.
In July 2015, the US Food and Drug Administration (FDA) approved brexpiprazole for the treatment of schizophrenia and as a combination therapy to treat major depressive disorder (MDD).
Health Canada approved brexpiprazole for schizophrenia in February this year, while the Australian Department of Health granted approval for the same indication in May.
Bexpiprazole is distributed and marketed under the brand name Rexulti in the US, Canada and Australia.