Phase 3 Results Show Reduced Agitation in Alzheimer Patients

A phase 3 study of an investigational drug, AVP-786, found that the treatment performed well compared to placebo in treating moderate-to-severe agitation in patients with Alzheimer-related dementia. The study results showed a significant improvement on the study’s primary endpoint on the Cohen-Mansfield Agitation Inventory for one of the doses tested. The other dose produced numerical, but not statistically significant improvement.

The agitation many patients with Alzheimer disease experience includes excessive motor activity, verbal aggression, and physical aggression, which impact the patient as well as caregivers.

"These initial data from the first phase 3 study are encouraging and we look forward to continuing to evaluate AVP-786 for the treatment of moderate-to-severe agitation in patients with Alzheimer's dementia as the clinical program progresses," said Sanjay Dubé, MD, Vice President, Research & Development, Head of Clinical Development & Scientific Strategy, Avanir Pharmaceuticals, Inc, in a statement.

Dubé noted that there is currently no treatment for agitation in patients with Alzheimer disease dementia that is approved by the US Food and Drug Administration (FDA).

"Any advancement in the treatment and management of agitation in patients with Alzheimer's dementia would help to bridge the treatment gap in these patients,” added Dubé.

The 12-week, double-blind, placebo-controlled study included 410 patients with moderate-to-severe agitation and probably Alzheimer disease dementia who were living in the community or in institutional care settings. Participants, aged 50 to 90 years, were randomized to either of 2 doses of AVP-786 or placebo for stage 1, a period of 6 weeks. For the 6 weeks of stage 2, participants receiving active treatment continued to receive the same dose of AVP-786. Patients receiving placebo in stage 1 were randomized (1:1:1) to either dose of AVP-786 or placebo for stage 2.

The company stated that only placebo-non-responders were used in the analysis, in an effort to reduce the influence of a placebo effect.

The safety data showed that the most common adverse events occurring in >5% incidence in either of the 2 doses of AVP-786 were falls, urinary tract infection, headache and diarrhea. There was low overall mortality during the study and no deaths were determined to be related to the treatment.

“It is important to note, that there are 2 additional phase 3 studies ongoing in the clinical development program, which use a conventional parallel-arm design, as opposed to the Sequential Parallel Comparison Design used in this first study. We will continue to analyze the full set of data from this first study and plan to communicate more about the results at the time of publication in a peer-reviewed journal," said Dubé.

Other phase 3 studies of AVP-786 for agitation in patients with Alzheimer disease dementia are currently recruiting participants, and the company is planning a long-term extension study that will extend approximately 56 weeks.