A Phase 2a Combined Open-Label and Double-Blind, Placebo-Controlled Crossover Study Assessing the Effectiveness, Safety, and Tolerability of Oral Fasudil in Subjects With Dementia and Wandering Behaviors of Elopement and/or Getting Lost
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 11
- 主要终点
- Change in Global Impression of Wandering (GIW) after oral Fasudil vs placebo in the Double-Blind Phase
研究概览
简要总结
Fasudil, a Rho kinase inhibitor, is believed to reduce wandering behaviors of elopement and getting lost by improving spatial memory and navigation through improvements in hippocampal blood flow. Fasudil is non-sedating.
The aim of the study is to assess the effectiveness of oral fasudil in reducing wandering behaviors of elopement and/or getting lost in subjects with dementia. In addition, effects on wandering behaviors of excess movement and pacing, cognition, memory, neuropsychiatric symptomatology, caregiver/nursing staff burden, and the safety and tolerability of fasudil treatment will be assessed.
详细描述
The study population will consist of subjects with dementia and wandering behaviors of elopement and/or getting lost. While it is anticipated that most participants will be residing at home (with caregiver support), subjects may live in another setting such as a group home, an assisted living unit, or in a long-term care facility, provided that a caregiver, formal or informal, has sufficient contact with the subject to permit accurate completion of the necessary assessments.
Enrolled subjects will enter the Open-Label Phase and receive treatment with fasudil 90 mg/day (30 mg three times daily [tid]) for 6 weeks in Open-Label Period 1. Responders (i.e., subjects who improve 2 points or more on the GIW) will proceed to the Double-Blind Phase. Subjects in whom fasudil is well-tolerated (i.e. subjects with ≤ 2 drug-related AEs of mild intensity, no drug-related AEs of greater than mild intensity, and creatinine level of < 1.5 mg/dL at all times during the period) and who do not respond will enter Open-Label Period 2, and be dosed with fasudil 180 mg/day (60 mg tid) for 6 weeks. Responders will proceed to the Double-Blind Phase and non-responders will move to the final post-treatment visit. In the Double-Blind Phase, subjects will receive treatment with either placebo or the dose they responded to in the Open-Label Phase (90 mg/day or 180 mg/day) for 6 weeks (Double-Blind Period 1), following which treatment assignment will be crossed over for 6 weeks (Double-Blind Period 2). A final post-treatment visit will occur 14 days after the last dose of study drug. Visits may be performed by qualified healthcare professionals at home or other care setting, or at a doctor's office/clinic. Interviews may be performed by telephone and/or telemedicine as appropriate.
Study Endpoints:
Primary:
• The Global Impression of Wandering (GIW)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Periods 1 and 2 of the open-label phase will be unblinded.
Periods 3 and 4 are double-blind crossover phases.
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
- •50 to 90 years of age (inclusive).
- •Diagnosis of dementia of any etiology.
- •MMSE 9-24 (inclusive).
- •Presence of one or both of the following wandering behaviors that in the opinion of the investigator, in consultation with caregiver, is at least of moderate severity (defined as clearly a wanderer, and this causes some distress or difficulty for both the subject and caregiver):
- •Elopes or attempts to elope AND/OR
- •Gets lost or is unable to locate a specific place.
- •Independently ambulatory with or without assistive devices (such as canes or walkers). Subjects must not require assistance to transfer out of bed or a chair.
- •Subject has a caregiver who has more than 10 hours/week of contact with the subject, is fluent and literate in English and is willing to accept responsibility for supervising the treatment (e.g., administering study drug) and assessing the condition of the subject throughout the study in accordance with all protocol requirements.
- •Consent obtained from the participant/legally authorized representative (LAR) in accordance with local regulations.
排除标准
- •Expected change in medication that could interfere with the study or free movement of the subject.
- •Serum creatinine ≥ 1.5 mg/dL.
- •ALT and/or alkaline aminotransferase (AST) ≥ 2 X and/or alkaline phosphatase (ALP) ≥ 1.5 upper limit of normal.
- •Blood pressure < 90/
- •On more than one of the following drug classes: long-acting nitrates, beta-blockers, or calcium channel blockers.
- •Any severe comorbidity that in the opinion of the Investigator would disallow safe participation in the trial.
- •Women of child-bearing potential; females must be postmenopausal or surgically sterilized.
- •Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data.
- •Planned change in the current living setting during the study.
- •History within the last year of either two or more falls leading to clinically significant injuries or one or more fall leading to hospitalization, and/or evidence of orthostatic hypotension.
- •Participation in another investigational drug study within 30 days before start of Open-Label period.
- •Subjects who, in the opinion of the investigator, are not suitable for the study.
研究组 & 干预措施
Oral Fasudil 90 mg/day
Subjects will receive a daily dose of 90 mg Fasudil for 42 days (open-label period 1). After Period 1 is complete, if the subject is a responder to Fasudil 90 mg/day, they will be randomized to either Fasudil 90 mg/day or a placebo for 6 weeks (double-blind period 1), then crossover to the other arm for 6 weeks (double-blind period 2).
干预措施: Oral Fasudil 90 mg/day (Drug)
Oral Fasudil 90 mg/day
Subjects will receive a daily dose of 90 mg Fasudil for 42 days (open-label period 1). After Period 1 is complete, if the subject is a responder to Fasudil 90 mg/day, they will be randomized to either Fasudil 90 mg/day or a placebo for 6 weeks (double-blind period 1), then crossover to the other arm for 6 weeks (double-blind period 2).
干预措施: Oral Placebo (Drug)
Oral Fasudil 180 mg/day
If the subject is a not a responder in the open-label period 1 but tolerated Fasudil 90 mg/day, they will be escalated to Fasudil 180 mg/day (open-label period 2) for 42 days. If the subject is a responder to Fasudil 180 mg/day, they are randomized to either Fasudil 180 mg/day for 42 days or a placebo (double-blind period 1), then crossover to the other arm for 6 weeks (double-blind period 2).
干预措施: Oral Fasudil 180 mg/day (Drug)
Oral Fasudil 180 mg/day
If the subject is a not a responder in the open-label period 1 but tolerated Fasudil 90 mg/day, they will be escalated to Fasudil 180 mg/day (open-label period 2) for 42 days. If the subject is a responder to Fasudil 180 mg/day, they are randomized to either Fasudil 180 mg/day for 42 days or a placebo (double-blind period 1), then crossover to the other arm for 6 weeks (double-blind period 2).
干预措施: Oral Placebo (Drug)
Oral Placebo
Placebo comparator arm to investigational drug (Fasudil 90 mg/day or 180 mg/day).
干预措施: Oral Fasudil 90 mg/day (Drug)
Oral Placebo
Placebo comparator arm to investigational drug (Fasudil 90 mg/day or 180 mg/day).
干预措施: Oral Fasudil 180 mg/day (Drug)
Oral Placebo
Placebo comparator arm to investigational drug (Fasudil 90 mg/day or 180 mg/day).
干预措施: Oral Placebo (Drug)
结局指标
主要结局
Change in Global Impression of Wandering (GIW) after oral Fasudil vs placebo in the Double-Blind Phase
时间窗: Week 6 and Week 12 of the Double-Blind period
The GIW is a variant of the 7-point Clinical Global Impression-Severity (CGI-S) scale and is used in FOUND specifically to obtain the investigator's overall assessment of severity of the subject's wandering behavior.
次要结局
- Change in blood pressure(Through study completion, up to 26 weeks)
- Change in body weight(Through study completion, up to 26 weeks)
- Change in body temperature(Through study completion, up to 26 weeks)
- Serious Adverse Events (SAEs)(Through study completion, up to 26 weeks)
- Change in heart rhythm(Through study completion, up to 26 weeks)
- Change in blood chemistry(Through study completion, up to 26 weeks)
- Change in liver function(Through study completion, up to 26 weeks)
- Adverse Events (AEs)(Through study completion, up to 26 weeks)
- Change in the Revised Algase Wandering Scale - Community Version (RAWS-CV)(Week 6 and Week 12 of the Double-Blind period)
- Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C)(Week 6 and Week 12 of the Double-Blind period)
- Center for Neurological Study-Lability Scale (CNS-LS)(Week 6 and Week 12 of the Double-Blind period)
- Zarit Burden Interview (ZBI)(Week 6 and Week 12 of the Double-Blind period)
- Change in Weekly Wandering Report - Community Version (WWR-C)(Weekly during the 12 weeks of the Double-Blind period)
- Change in Mini Mental State Examination (MMSE)(Week 6 and Week 12 of the Double-Blind period)
- Change in Neuropsychiatric Inventory-Questionnaire (NPI-Q)(Week 6 and Week 12 of the Double-Blind period)
- Change in blood parameters(Through study completion, up to 26 weeks)
- Change in urine contents(Through study completion, up to 26 weeks)
- Change in respiratory rate(Through study completion, up to 26 weeks)
- Columbia Suicide Severity Rating Scale (C-SSRS)(Through study completion, up to 26 weeks)