A Phase 2, Randomized, Double-dummy, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of AVP-923 (Dextromethorphan/Quinidine) for the Treatment of Symptoms of Agitation in Patients With Alzheimer's Disease.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 220
- 主要终点
- Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
研究概览
简要总结
The objectives of the study are to evaluate the safety, tolerability and efficacy of AVP-923 compared to placebo, for the treatment of symptoms of agitation in participants with Alzheimer's Disease (AD).
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, double-dummy, double-blind, placebo-controlled study, consisting of 10 weeks of treatment.
Up to 200 participants will be enrolled at approximately 30-40 centers in the US.
Study medication will be administered orally twice-daily from Day 1 through Day 70. Screening must occur within 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).
- •The participant has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.
- •Either out-patients or residents of an assisted-living facility or a skilled nursing home.
- •CGI-S score is ≥ 4 (moderately ill) at screening and baseline.
- •Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive).
- •Caregiver who is able and willing to comply with all required study procedures, ensuring that the participant attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the participant for a minimum of 4 hours on 4 separate days per week.
排除标准
- •Participant has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia).
- •Participant 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, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).
- •Participant with myasthenia gravis.
研究组 & 干预措施
Placebo then AVP-923
Participants will receive placebo in Stage 1 followed by AVP-923 in Stage 2.
干预措施: AVP-923-30 (Drug)
Placebo
Participants will receive placebo during Stage 1 and Stage 2 of the study.
干预措施: Placebo (Drug)
AVP-923
Participants will receive AVP-923-20 and AVP-923-30 in a sequential manner during Stage 1 and Stage 2 of the study.
干预措施: AVP-923-20 (Drug)
AVP-923
Participants will receive AVP-923-20 and AVP-923-30 in a sequential manner during Stage 1 and Stage 2 of the study.
干预措施: AVP-923-30 (Drug)
Placebo then AVP-923
Participants will receive placebo in Stage 1 followed by AVP-923 in Stage 2.
干预措施: AVP-923-20 (Drug)
Placebo then AVP-923
Participants will receive placebo in Stage 1 followed by AVP-923 in Stage 2.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
时间窗: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Data are reported for only those participants contributing data to the analysis.
次要结局
- Number of Participants With the Indicated Type of Adverse Event(up to Week 10)
- Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Number of Participants Using Rescue Medications(up to Week 10)
- Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57(Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57)
- Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)(Day 36 (Stage 2 Baseline); Day 70)
- Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)(Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70)
- Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)(Day 1 (Stage 1 Baseline); Day 70)
- Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use(up to Week 10)