A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan 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
- 终止
- 入组人数
- 241
- 试验地点
- 106
- 主要终点
- Change From the End of Period A (Week 1) to Week 10 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
研究概览
简要总结
This study was conducted to evaluate the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) compared to placebo for the treatment of agitation in participants with dementia of the Alzheimer's type.
详细描述
Eligible participants for this study had a diagnosis of probable Alzheimer's disease (AD) and had clinically significant, moderate/severe agitation secondary to AD.
This was multicenter, randomized, double-blind, placebo-controlled study, consisting of 12 weeks of treatment. Screening occurred within 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were randomized into the study.
241 participants were enrolled into the study.
Study medication was administered orally twice daily from Day 1 through Day 85.
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
- •Participants with a diagnosis of probable Alzheimer's disease according to the 2011 Neuropsychiatric Inventory Agitation/Aggression (NPI-AA) working groups criteria
- •Participants with clinically significant, moderate-to-severe agitation for at least 2 weeks prior to Screening that interferes with daily routine per the Investigator's judgment
- •Participants who require pharmacotherapy for the treatment of agitation per the Investigator's judgment after an evaluation of reversible factors and a course of nonpharmacological interventions
- •Diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation.
- •Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators and staff
- •Participants with a reliable caregiver who is able and willing to comply with all study procedures, including adherence to administering study drug and not administering any prohibited medications during the course of the study, and who spends a minimum of 2 hours per day for 4 days per week with the participant
排除标准
- •Participants with dementia predominantly of the non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
- •Participants with symptoms of agitation that are not secondary to Alzheimer's dementia (e.g., secondary to pain, other psychiatric disorder, or delirium)
- •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 [except skin basal-cell carcinoma], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
- •Participants with myasthenia gravis
研究组 & 干预措施
AVP-786-42.63
Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.
干预措施: AVP-786 (Drug)
Placebo
Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786 matching placebo capsules, twice a day, for 11 weeks in Period B.
干预措施: Placebo (Drug)
AVP-786-18
Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-18 (d6-DM 18 milligrams (mg)/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.
干预措施: AVP-786 (Drug)
结局指标
主要结局
Change From the End of Period A (Week 1) to Week 10 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
时间窗: Week 1 to Week 10
The CMAI is used to assess the frequency of manifestations of agitated behaviors in elderly persons. It consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. These distinct agitation syndromes include aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Each of the 29 items is rated on a 7-point scale of frequency (1 = never, 2 = less than once a week but still occurring, 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 ratings are based on the 2 weeks preceding assessment of the CMAI. Higher scores indicate higher frequency of agitated behaviours while lower scores indicate lower frequency of agitated behaviours.
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE
时间窗: From randomization (Week 2) up to 30 days after last dose of study drug (Up to Week 16)
An adverse event (AE) is any untoward medical occurrence or unintended change (eg, physical, psychological, or behavioral), including inter-current illness, that does not necessarily have a causal relationship with the study treatment. A serious adverse event (SAE) is any AE occurring at any dose that results in death, life-threatening experience, persistent or significant disability/incapacity, in-patient hospitalization or prolongation of hospitalization or congenital anomaly/birth defect. TEAEs are all AEs (including serious and non-serious) which started after start of double-blind study drug treatment; or if the event was continuous from baseline and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy.
次要结局
- Change From the End of Period A (Week 1) to Week 10 in the Clinical Global Impression of Severity of Illness (CGIS) Score, as Related to Agitation(Week 1 to Week 10)