Otsuka and Lundbeck announce decision to continue phase III clinical trial evaluating brexpiprazole for treatment of agitation in patients with Alzheimer's-type dementia

Tokyo, Japan and Valby, Denmark April 13, 2021 – Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announce the decision to continue the recruitment of patients in the phase III clinical trial of brexpiprazole in the treatment of agitation in patients with dementia of the Alzheimer's type (NCT03548584). The decision to continue the trial is based on the results of an independent interim analysis, supporting to progress the trial to the planned full enrollment of 330 patients.

The continuation of the study enables us to further explore the efficacy of brexpiprazole to address the high medical need in patients suffering from agitation in Alzheimer’s-type dementia. Completion of the trial is expected in the first half of 2022.

About the study

Trial 331-14-213 (NCT03548584; Trial 213) was designed to assess the safety, tolerability and efficacy of brexpiprazole in the treatment of patients with agitation in Alzheimer’s dementia. The trial consists of a 12-week double-blind treatment period with a 30-day follow-up. The trial population is planned to include 330 male and female patients, aged 55 to 90 years (inclusive), with a diagnosis of probable Alzheimer’s disease.

The primary outcome is the change in the CMAI total score. The key secondary outcome is the change in the Clinical Global Impression – Severity of Illness (CGI-S) score, as related to symptoms of agitation. Patients participating in the trial are from countries including Bulgaria, Hungary, Serbia, Slovakia, Spain, Ukraine, and the U.S. Approximately half of the participants are living at home and the rest are institutionalized.

As agreed with the FDA, an interim analysis conducted by an independent data monitoring committee assessed the efficacy on the CMAI total score, in accordance with pre-specified criteria when 255 subjects had completed the trial.

About brexpiprazole

Brexpiprazole is approved as an adjunctive therapy for the treatment of adults with major depressive disorder and as a treatment for adults with schizophrenia in countries such as the U.S. and Canada. In Europe and Japan, the product is approved for schizophrenia. In addition, brexpiprazole has been approved in over 20 other countries and regions across the world. Brexpiprazole is distributed and marketed under the brand name Rexulti®. In Europe, brexpiprazole is distributed and marketed under the brand name Rxulti®.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action for brexpiprazole in the adjunctive treatment of major depressive disorder or schizophrenia is not fully understood. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. Brexpiprazole exhibits high affinity (sub-nanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors.

Otsuka and Lundbeck are grateful to the patients with Alzheimer´s disease, their families, and the investigators who participated in the trials and contributed greatly to this research.

Otsuka Contacts

In U.S.:

In Japan:

Robert Murphy                              

Jeffrey Gilbert

Director, External Communications

Leader, Pharmaceutical PR          



Lundbeck contacts



Palle Holm Olesen

Juliane Lenzner

Vice President, Investor Relations

Vice President, Corporate Communication

+45 30 83 24 26

+45 36 43 40 00

About Otsuka Pharmaceutical

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: “Otsuka–people creating new products for better health worldwide.” Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka Pharmaceutical is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.3 billion in 2020.

About H. Lundbeck A/S

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in brain diseases. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best.

Millions of people worldwide live with brain diseases, and far too many suffer due to inadequate treatment, discrimination, a reduced number of working days, early retirement, and other unnecessary consequences. Every day, we strive for improved treatment and a better life for people living with brain diseases – we call this Progress in Mind.

Read more at .

Our approximately 5,600 employees in more than 50 countries are engaged in the entire value chain throughout research, development, production, marketing, and sales. Our pipeline consists of several R&D projects, and our products are available in more than 100 countries. We have research facilities in Denmark and the U.S., and our production facilities are located in Denmark, France, and Italy. Lundbeck generated revenue of DKK 17.7 billion in 2020 (EUR 2.4 billion; USD 2.7 billion).

For additional information, we encourage you to visit our corporate site, and connect with us on Twitter at @Lundbeck and via LinkedIn.