New Phase 3 Study Planned for Possible Treatment of Agitation Linked to Alzheimer’s

Otsuka Pharmaceutical announced that it and Lundbeck will launch a third Phase 3 clinical trial of brexpiprazole to possibly treat agitation in patients with dementia linked to probable Alzheimer’s disease.

Brexpiprazole, under the brand name Rexulti, was approved in the United States to treat people with schizophrenia and as an adjunct treatment for patients with major depressive disorder (MDD) in July 2015. It was approved in Canada and Australia to treat schizophrenia in 2017 and is marketed there under the same brand name.

The decision to initiate a third clinical trial follows conversations with the U.S. Food and Drug Administration (FDA) regarding two prior Phase 3 studies (NCT01862640 and NCT01922258) for agitation in people with a diagnosis of probable Alzheimer’s, the company said in a press release.  Both were completed this year.

The first study evaluated the efficacy, safety and tolerability of two fixed and daily doses of brexpiprazole, 1 or 2 mg, or placebo, and the second evaluated the efficacy, safety and tolerability of 0.5 mg, 1 mg or 2 mg of brexpiprazole or placebo each day.

Both trials were randomized and double-blind, and enrolled a total of nearly 700 people between ages 51 and 90 with a diagnosis of probable Alzheimer’s disease (AD) and symptoms of agitation.

Top-line results were reported by Lundbeck in May. In both studies, treated patients showed improvements in symptoms of agitation, compared to placebo, as measured by changes from baseline, or study start, in the Cohen-Mansfield Agitation Inventory (CMAI) total score, a 29-item scale to assess agitation. But improvements documented were less robust in the second clinical trial than in the first.

Regarding safety and tolerability, both studies confirmed the profile of brexpiprazole as observed in earlier clinical studies in people with schizophrenia and MDD.

The newest Phase 3 study is expected to begin by summer 2018.

Agitation is one of the most frequent symptoms of Alzheimer’s-related dementia, as is wandering, restlessness, aggressive behaviors, and irritability, according to a study published in 2012. Agitation places a considerable burden on caregivers. The symptom is often pointed as a determining factor in the decision to place patients in high-level residential care facilities.

Brexpiprazole was discovered by Otsuka, and is being co-developed by Otsuka and Lundbeck. Its mechanism of action is not fully understood.