Fasudil fOr redUcing elopemeNt and Spatial Disorientation

Dementia Clinical Trial

— FOUND  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04793659
• Other study ID #: WP-0512-001
• Status: Completed
• Phase: Phase 2
• Start date: December 15, 2020
• Est. completion date: February 11, 2022

Study information

• Verified date: July 2022
• Source: Woolsey Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 11, 2022
• Est. primary completion date: December 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dementia

Intervention

Drug:
• Oral Fasudil 90 mg/day
Oral tablet
• Oral Fasudil 180 mg/day
Oral tablet
• Oral Placebo
Oral tablet

Locations

Country	Name	City	State
Australia	Barwon Geriatrics	Geelong	Victoria
Australia	Modbury Hospital	Modbury	South Australia
Australia	GV Health	Shepparton	Victoria
Australia	Northeast Health Wangaratta	Wangaratta	Victoria
Australia	Neurodegenerative Disorders Research	West Perth	Western Australia
United States	Albuquerque Neuroscience Inc.	Albuquerque	New Mexico
United States	Re:Cognition Health	Fairfax	Virginia
United States	Accel Research Sites	Lakeland	Florida
United States	Lakes Research, LLC.	Miami Lakes	Florida
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Bio Behavioral Health	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Woolsey Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Global Impression of Wandering (GIW) after oral Fasudil vs placebo in the Double-Blind Phase	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.	Week 6 and Week 12 of the Double-Blind period
Secondary	Change in Weekly Wandering Report - Community Version (WWR-C)	The WWR-C is composed of targeted questions related to excess walking, spontaneous pacing, elopement, and wayfinding; it is designed to be assessed on a weekly basis by caregivers about subjects for whom they care. The WWR-C asks the caregiver to rate the subject's behavior for the previous week.	Weekly during the 12 weeks of the Double-Blind period
Secondary	Change in the Revised Algase Wandering Scale - Community Version (RAWS-CV)	The RAWS-CV is a 40-item tool with 6 subscales to assess wandering behaviors (eloping behaviors, negative outcomes, mealtime impulsivity, persistent walking, repetitive walking, and spatial disorientation), and a total score scale.	Week 6 and Week 12 of the Double-Blind period
Secondary	Change in Mini Mental State Examination (MMSE)	The MMSE is a 30-point questionnaire that is used to measure cognitive impairment.	Week 6 and Week 12 of the Double-Blind period
Secondary	Change in Neuropsychiatric Inventory-Questionnaire (NPI-Q)	The NPI-Q provides an assessment of dementia-related emotional behavioral symptomatology in routine clinical practice settings. Caregiver distress is also assessed.; The NPI-Q asks the assessor to rate the previous 30 days. At the Final Visit, the assessor will rate the NPI-Q for the 2-week period following the final dose. The scale is completed by the caregiver without input from the subject. All reasonable efforts should be made to ensure each NPI-Q for an individual subject is completed by the same caregiver to minimize inter-rater variability.	Week 6 and Week 12 of the Double-Blind period
Secondary	Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C)	The CMAI-C is a 37-item scale to systematically assess agitation.	Week 6 and Week 12 of the Double-Blind period
Secondary	Center for Neurological Study-Lability Scale (CNS-LS)	The CNS-LS is a 7-item questionnaire to assess perceived frequency of pseudobulbar affect episodes.	Week 6 and Week 12 of the Double-Blind period
Secondary	Zarit Burden Interview (ZBI)	The ZBI is a 22-item scale to assess caregiver burden.	Week 6 and Week 12 of the Double-Blind period
Secondary	Adverse Events (AEs)		Through study completion, up to 26 weeks
Secondary	Serious Adverse Events (SAEs)		Through study completion, up to 26 weeks
Secondary	Change in blood pressure		Through study completion, up to 26 weeks
Secondary	Change in blood parameters	Hematology: white blood cell count, hemoglobin, hematocrit, platelet count	Through study completion, up to 26 weeks
Secondary	Change in blood chemistry	Blood chemistry: glucose, sodium, potassium, bicarbonate, blood urea nitrogen, creatinine, cystatin c	Through study completion, up to 26 weeks
Secondary	Change in liver function	Liver function tests: albumin, total bilirubin, direct bilirubin, ALP, AST, ALT, gamma glutamyl transferase, lactate dehydrogenase	Through study completion, up to 26 weeks
Secondary	Change in urine contents	Urinalysis (occult blood, protein)	Through study completion, up to 26 weeks
Secondary	Change in heart rhythm	12-lead Electrocardiogram (ECG) will be used to obtain a record of cardiac activity	Through study completion, up to 26 weeks
Secondary	Change in body weight		Through study completion, up to 26 weeks
Secondary	Change in body temperature		Through study completion, up to 26 weeks
Secondary	Change in respiratory rate		Through study completion, up to 26 weeks
Secondary	Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is an assessment used to identify immediate risk of suicide, and is completed following the patient interview, review of medical record(s) and/or consultation with family members and/or other professionals. While the C-SSRS is a detailed interview, the full interview is needed only if the initial screening questions about suicidal ideation and behavior are positive.; In subjects with severe cognitive impairment, i.e., so substantial as to interfere with an understanding of the concept of suicide, the C-SSRS may be omitted.	Through study completion, up to 26 weeks