A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterated [d6]-Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 522
- 试验地点
- 81
- 主要终点
- Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
研究概览
简要总结
Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) will be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.
详细描述
Eligible participants for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD.
This is a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.
Approximately 470 participants will be enrolled at approximately 75 centers in North America.
Study medication will be administered orally twice-daily from Day 1 through Week 12 (Day 85). Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.
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
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria
- •The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization
- •The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
- •Either out participants or residents of an assisted-living facility or a skilled nursing home
- •Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is >=4 (moderately ill) at screening and baseline
- •Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline
- •Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant.
排除标准
- •Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
- •Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
- •Participant with myasthenia gravis
研究组 & 干预措施
Placebo
Participants were administered AVP-786 matching placebo capsules, orally, twice daily (BID) for up to 12 weeks.
干预措施: Placebo (Drug)
AVP-786-28
Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.
干预措施: AVP-786-18 (Drug)
AVP-786-28
Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.
干预措施: AVP-786-28 (Drug)
AVP-786-42.63
Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.
干预措施: AVP-786-28 (Drug)
AVP-786-42.63
Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.
干预措施: AVP-786-42.63 (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
时间窗: Baseline, Week 12
The CMAI was used to assess the frequency of manifestations of agitated behaviors in elderly participants. It consists of 29 agitated items rated on a 7-point scale of frequency: 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. Negative change from baseline indicates improvement. Mixed Model Repeated Measures (MMRM) was used for the analysis.
次要结局
- Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score(Baseline, Week 12)
- Number of Participants With the Change From Baseline in the General Medical Health Rating (GMHR) Score at Week 12(Week 12)
- Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the NPI Irritability/Lability Domain Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Overall Rating(Baseline, Week 12)
- Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score(Baseline, Week 12)
- Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score(Baseline, Week 12)
- Relative Change From Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score(Baseline, Week 12)
- Change From Baseline to Week 12 in the NPI Total Score(Baseline, Week 12)
- Resource Utilization in Dementia (RUD) Score: Number of Hours Per Day the Caregiver Spent Assisting the Participant(Week 12)
- Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant(Week 12)
- Resource Utilization in Dementia (RUD) Score: Number of Visits to Hospital, Emergency, and Healthcare Professional(Week 12)