H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced positive results of the phase III clinical trial of brexpiprazole in the treatment of agitation in patients with Alzheimer's dementia (NCT03548584). The analysis concluded that there is a statistically significant difference (p=0.0026) in the mean change from baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) total score between brexpiprazole and placebo. Full study results are not yet available.
Further prespecified and exploratory analyses of the data set will be conducted to determine the full potential of brexpiprazole in the treatment of agitation in patients with Alzheimer's dementia. Based on this outcome Lundbeck and Otsuka are planning a regulatory filing to the FDA later in 2022. The Supplemental New Drug Application will be comprised of this study as well as two earlier trials.
In February 2016, the FDA granted fast track designation for brexpiprazole for treatment of agitation in patients with Alzheimer's dementia. Lundbeck and Otsuka are incredibly grateful to all the patients with Alzheimer´s dementia, their families, caregivers, and the investigators who participated in the trials and contributed greatly to this research. The trial results are planned to be submitted for scientific publication at a later date.
Trial 331-14-213 (NCT03548584; Trial 213) was designed to assess the safety, tolerability and efficacy of two fixed doses of brexpiprazole (2 mg/day and 3 mg/day) in the treatment of patients with agitation in Alzheimer's dementia. The trial consisted of a continuous 12-week double-blind treatment period with a 30-day follow-up. The randomized trial population included 345 male and female patients, aged 55-90 years (inclusive), with a diagnosis of probable Alzheimer's disease, and meeting criteria of agitation as defined by the International Psychogeriatric Association (IPA).
The primary outcome was the change in the CMAI total score at week 12 for all patients treated with brexpiprazole versus those treated with placebo. The key secondary outcome was the change in the Clinical Global Impression - Severity of Illness (CGI-S) score, as related to symptoms of agitation. Participating countries include Bulgaria, Hungary, Serbia, Slovakia, Spain, Ukraine, and USA.
The study included both patients who were living at home and those living in institutionalized settings. In the study, the improvements from baseline on the primary endpoint of CMAI for patients receiving brexpiprazole or 2 mg/day or 3 mg/day were statistically greater than for those receiving placebo (p=0.0026). This result was supported by a statistically superior improvement on the key secondary endpoint of CGI-S, as related to agitation (p=0.0055).
Brexpiprazole was generally well tolerated, and no new safety signals were observed. The only Treatment Emergent Adverse Event (TEAE) with more than 5% incidence in patients treated with brexpiprazole was headache (6.6% vs. 6.9% for placebo).
The following TEAEs occurred at an incidence of at least 2% in brexpiprazole treatment group and greater than that of placebo: somnolence, nasopharyngitis, dizziness, diarrhea, urinary tract infection, and asthenia. There was one death observed in the 3 mg/day treatment group, assessed as not related to treatment by the investigator.