Fasudil fOr redUcing elopemeNt and Spatial Disorientation (FOUND)

Woolsey Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Dementia

Treatments: Drug: Oral Fasudil 90 mg/day; Drug: Oral Fasudil 180 mg/day; Drug: Oral Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04793659

WP-0512-001

Details and patient eligibility

About

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.

Full 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

Enrollment: 24 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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24 participants in 3 patient groups, including a placebo group

Oral Fasudil 90 mg/day

Experimental group

Description:

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).

Treatment:

Drug: Oral Placebo

Drug: Oral Fasudil 90 mg/day

Oral Fasudil 180 mg/day

Experimental group

Description:

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).

Treatment:

Drug: Oral Placebo

Drug: Oral Fasudil 180 mg/day

Oral Placebo

Placebo Comparator group

Description:

Placebo comparator arm to investigational drug (Fasudil 90 mg/day or 180 mg/day).

Treatment:

Drug: Oral Placebo

Drug: Oral Fasudil 90 mg/day

Drug: Oral Fasudil 180 mg/day