A Phase 3, 12-Week, Multicenter, Randomized, Double-blind, Placebo-controlled, 2-Arm, Fixed-dose Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 345
- 试验地点
- 1
- 主要终点
- Change From Baseline to Week 12 in the CMAI Total Score
研究概览
简要总结
This study compares the efficacy of 2 doses of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type.
详细描述
This is a phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose trial designed to assess the efficacy, safety, and tolerability of brexpiprazole compared with placebo. The trial consists of a 12-week double-blind treatment period with a 30 day follow-up. The trial population will include male and female participants between 55 and 90 years of age (inclusive) with a diagnosis of probable Alzheimer's disease, who are residing either in an institutionalized setting or in a non-institutionalized setting where the participant is not living alone. This trial will analyze data gathered from approximately 330 participants at multiple countries. Participants may also be eligible to enter an active treatment extension trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a diagnosis of probable Alzheimer's disease.
- •Participants with a diagnosis of agitation
- •Participants with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.
- •Participants with a previous MRI or CT scan of the brain, that was performed after the onset of symptoms of dementia, with findings consistent with a diagnosis of Alzheimer's disease.
- •Participants who are residing at their current location for at least 28 days before screening and are expected to remain at the same location for the duration of the trial.
- •Institutionalized participants with an identified caregiver who has sufficient contact (minimum of 2 hours per day for 4 days per week) to describe the participant's symptoms and has direct observation of the participant's behavior. Non-institutionalized participants may not be living alone and must have an identified caregiver who has sufficient contact (minimum of 2 hours per day for 4 days per week) to describe the participant's symptoms and has direct observation of the participant's behavior.
- •Participants with onset of symptoms of agitation at least 2 weeks prior to screening visit.
- •Participants will and able to discontinue all prohibited concomitant medications to meet protocol required washouts prior to and during the trial period.
排除标准
- •Participants with dementia or other memory impairment not due to Alzheimer's disease.
- •Participants with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
- •Participants who had an insufficient response, based on the investigator's judgment, to 2 or more previous antipsychotic medications.
- •Participants who have been diagnosed with an Axis I disorder.
- •Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
- •Participants with uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension.
- •Participants with diabetes mellitus (insulin-dependent and non-insulin-dependent) may be eligible for the trial if their condition is stable and well-controlled.
研究组 & 干预措施
Placebo
Participants received matching placebo, once daily for 12 weeks.
干预措施: Placebo (Other)
Brexpiprazole 2 mg
Participants followed a titration schedule, to gradually increase their dose from 0.5 milligrams per day (mg/day) in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 milligrams (mg), once daily until Week 12.
干预措施: Brexpiprazole (Drug)
Brexpiprazole 3 mg
Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 3 mg/day from Day 29. Participants continued to receive brexpiprazole 3 mg, once daily until Week 12.
干预措施: Brexpiprazole (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in the CMAI Total Score
时间窗: Baseline and Week 12
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. Mixed model repeated measures (MMRM) was used for the analysis. As prespecified in the statistical analysis plan (SAP), data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
次要结局
- Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation(Baseline and Week 12)
- Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period(Baseline, Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period(Baseline, Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period(Baseline, Weeks 2, 4, 6, 8, 10, and 12)
- CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period(Baseline, Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline to Week 12 in CMAI Subscale Scores(Baseline and Week 12)
- CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period(Weeks 2, 4, 6, 8, 10, and 12)
- CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period(Baseline, Weeks 2, 4, 6, 8, 10, and 12)