Background

Brexpiprazole is an orally available dopamine receptor D2 partial agonist. This quinolinone derivative is a successor to aripiprazole (Abilify, Aripiprex), an approved, widely used drug that is also a dopamine D2 receptor partial agonist. Brexpiprazole is being developed worldwide as an add-on therapy primarily for the treatment of depression and schizophrenia, but also for agitation and other behavioral symptoms in patients with Alzheimer's disease. In addition, it is being tested in people with attention deficit hyperactivity disorder.

Findings

In July 2013, Otsuka and Lundbeck started a Phase 3 study to evaluate brexpiprazole for the treatment of agitation in 560 patients with moderate to severe Alzheimer's dementia living in a nursing home, dementia unit, assisted living facility, or other residential care facility in the United States. The trial will compare the safety, efficacy, and tolerability of three months of treatment with 0.5, 1 and 2mg of brexpiprazole or placebo given as a fixed dose once daily. The primary endpoint is change from baseline in the Cohen-Mansfield Agitation Inventory, but the trial will also measure changes in aggression, global clinical status, and quality of life. In April 2015, this trial dropped the 0.5 mg dose and is continuing with a targeted enrollment of 420 patients. The trial offers a two-month safety follow-up study. 

In September 2013, a second Phase 3 trial started enrolling an anticipated 230 patients. This trial explores brexpiprazole using a flexible dose titrated between 0.5 to 2 mg/day depending on efficacy and tolerability in a given patient, but is otherwise identical. In June 2014, Otsuka added a 2-month followup study for participants in either of these two trials.

For all trials of brexpiprazole, see clinicaltrials.gov.

Clinical Trial Timeline