Clinical trial NCT04793659: Fasudil fOr redUcing elopemeNt and Spatial Disorientation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dementia
Keywords: Wandering Behavior
Dementia
Fasudil
Lead sponsor: Woolsey Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-03-11
Enrollment: 24
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Combined Open-Label and Double-Blind, Placebo-Controlled Crossover
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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)

Secondary:

* Weekly Wandering Report - Community Version (WWR-C)
* The Revised Algase Wandering Scale - Community Version (RAWS-CV)
* The Mini Mental State Examination (MMSE)
* The Neuropsychiatric Inventory-Questionnaire (NPI-Q)
* The Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C)
* The Center for Neurological Study-Lability Scale (CNS-LS)
* The Zarit Burden Interview (ZBI)
* Safety
* Tolerability

Eligibility criteria: Inclusion Criteria:

1. 50 to 90 years of age (inclusive).
2. Diagnosis of dementia of any etiology.
3. MMSE 9-24 (inclusive).
4. 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):

   1. Elopes or attempts to elope AND/OR
   2. Gets lost or is unable to locate a specific place.
5. 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.
6. 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.
7. Consent obtained from the participant/legally authorized representative (LAR) in accordance with local regulations.

Exclusion Criteria:

1. Expected change in medication that could interfere with the study or free movement of the subject.
2. Serum creatinine ≥ 1.5 mg/dL.
3. ALT and/or alkaline aminotransferase (AST) ≥ 2 X and/or alkaline phosphatase (ALP) ≥ 1.5 upper limit of normal.
4. Blood pressure \< 90/60.
5. On more than one of the following drug classes: long-acting nitrates, beta-blockers, or calcium channel blockers.
6. Any severe comorbidity that in the opinion of the Investigator would disallow safe participation in the trial.
7. Women of child-bearing potential; females must be postmenopausal or surgically sterilized.
8. 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.
9. Planned change in the current living setting during the study.
10. 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.
11. Participation in another investigational drug study within 30 days before start of Open-Label period.
12. Subjects who, in the opinion of the investigator, are not suitable for the study.

Primary outcomes:
measure: Change in Global Impression of Wandering (GIW) after oral Fasudil vs placebo in the Double-Blind Phase
timeFrame: Week 6 and Week 12 of the Double-Blind period
Secondary outcomes:
measure: Change in Weekly Wandering Report - Community Version (WWR-C)
timeFrame: Weekly during the 12 weeks of the Double-Blind period
measure: Change in the Revised Algase Wandering Scale - Community Version (RAWS-CV)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Change in Mini Mental State Examination (MMSE)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Change in Neuropsychiatric Inventory-Questionnaire (NPI-Q)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Center for Neurological Study-Lability Scale (CNS-LS)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Zarit Burden Interview (ZBI)
timeFrame: Week 6 and Week 12 of the Double-Blind period
measure: Adverse Events (AEs)
timeFrame: Through study completion, up to 26 weeks
measure: Serious Adverse Events (SAEs)
timeFrame: Through study completion, up to 26 weeks
measure: Change in blood pressure
timeFrame: Through study completion, up to 26 weeks
measure: Change in blood parameters
timeFrame: Through study completion, up to 26 weeks
measure: Change in blood chemistry
timeFrame: Through study completion, up to 26 weeks
measure: Change in liver function
timeFrame: Through study completion, up to 26 weeks
measure: Change in urine contents
timeFrame: Through study completion, up to 26 weeks
measure: Change in heart rhythm
timeFrame: Through study completion, up to 26 weeks
measure: Change in body weight
timeFrame: Through study completion, up to 26 weeks
measure: Change in body temperature
timeFrame: Through study completion, up to 26 weeks
measure: Change in respiratory rate
timeFrame: Through study completion, up to 26 weeks
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Through study completion, up to 26 weeks
Other outcomes:
Locations:
city: Stamford
country: United States
facility: New England Institute for Clinical Research
state: Connecticut
city: Lakeland
country: United States
facility: Accel Research Sites
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research, LLC.
state: Florida
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience Inc.
state: New Mexico
city: Fairfax
country: United States
facility: Re:Cognition Health
state: Virginia
city: Modbury
country: Australia
facility: Modbury Hospital
state: South Australia
city: Geelong
country: Australia
facility: Barwon Geriatrics
state: Victoria
city: Shepparton
country: Australia
facility: GV Health
state: Victoria
city: Wangaratta
country: Australia
facility: Northeast Health Wangaratta
state: Victoria
city: West Perth
country: Australia
facility: Neurodegenerative Disorders Research
state: Western Australia
Study officials:
References: