Otsuka Pharmaceutical Co., Ltd. (Otsuka) and its U.S. subsidiaries, Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) announce topline results of the phase 3 clinical trial of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer's disease (Trial 17-AVP-786-305; NCT03393520). A statistically significant difference was not achieved on the primary efficacy endpoint, mean change from baseline to week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) total score between AVP-786 and placebo.

There was one treatment-emergent adverse event (TEAE) with an incidence rate of more than 5% in patients treated with AVP-786 and greater than placebo which was Fall; 16 (8.6%) in AVP-786 high dose, 18 (9.1%) in AVP-786 low dose and 6 (2.8%) placebo. There were 4 deaths reported in the trial; 1 (0.5%) in the AVP-786 low dose group and 3 (1.4%) in the placebo group.

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 AVP-786 in the treatment of agitation associated with dementia due to Alzheimer's disease. Otsuka intends to submit the trial results for scientific publication at a later date.

"While the result of this trial is disappointing, we plan to analyze the full data set to determine the future potential of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer's disease. In 2023, Otsuka became the first company to get a drug approved for this patient population and we are committed to expanding and innovating in this area," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. "We are deeply grateful to all of the study participants, their caregivers, and the investigators who took part in this trial and contributed to this research."

About agitation associated with dementia due to Alzheimer's disease
Agitation associated with dementia due to Alzheimer's disease is a common neuropsychiatric symptom that is reported in approximately half of all patients with Alzheimer's dementia. The condition has a large impact on the quality of life for the patients, family members, and caregivers.^1,2 Agitation associated with dementia due to Alzheimer's disease covers a large group of behaviors such as pacing, gesturing, profanity, shouting, shoving, and hitting.³ Symptoms of this condition are also a consistent predictor of nursing home admission. ^4,5,6

REFERENCES

1. *1Halpern R et al. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry 2019; 34: 420-431
2. *2Fillit H et al. Impact of agitation in long-term care residents with dementia in the United States. Int J Geriatr Psychiatry 2021; 36: 1959-1969
3. *3Cummings J et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr 2015; 27: 7-17
4. *4Gaugler JE et al. Predictors of nursing home admission for persons with dementia. Med Care 2009; 47: 191-198
5. *5Kales HC et al. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005;13:441-449
6. *6Yaffe K et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002;287:2090 -2097