A Study to Evaluate the Safety and Efficacy of Basmisanil in Adults With Severe Motor Impairment Following an Ischemic Stroke

Study Overview
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Brief Summary
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This Phase IIa, randomized, double-blind, placebo-controlled, parallel group study will evaluate the safety, efficacy and pharmacodynamics of basmisanil in adult participants with severe motor impairment following an ischemic stroke.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Safety, Efficacy and Pharmacodynamic Study of Basmisanil (RO5186582) in Adults With Severe Motor Impairment Following an Ischemic Stroke

Conditions
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Stroke

Intervention / Treatment
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* Drug: Basmisanil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiologic assessment confirming an acute middle cerebral artery ischemic stroke Index stroke occurred within the past 3-4 days Inpatient males and females Severe hemiparesis or hemiplegia defined by FMMS score less than or equal to (</=) 35 Sufficient speech, vision and hearing to participate in study evaluations Exclusion Criteria: NIHSS greater than (>) 20 Severe aphasia that prevents a participant from following directions in rehabilitation Significant deficit from prior strokes or pre-existing motor deficit History of epilepsy, neurosurgery, severe head trauma or central nervous system infections that have residual symptomatology or have required treatment in the last 12 months Known or suspected clinical seizure post-index stroke History of pre-existing dementia or use of medications for dementia History of clinically significant pre-existing psychiatric conditions within 12 months prior to stroke Due to undergo carotid surgery within the next 4 months Enrollment/participation in any interventional study (clinical trial) involving an investigational drug (unapproved) or non-drug treatment within the prior 3 months or 6 times the half-life (whichever is longer) Clinically relevant medical conditions that would likely interfere with the study conduct and scheduled assessments Contraindication to magnetic resonance imaging (MRI) or conditions which render interpretation of MRI difficult

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Basmisanil<br>Basmisanil at a dose of 240 milligrams (mg) orally twice daily for 90 days. | Drug: Basmisanil<br>* Basmisanil immediate-release granules at a dose of 240 mg will be given orally twice daily for 90 days.<br>* Other names: RO5186582;|
| Placebo Comparator: Placebo<br>Placebo matched to basmisanil orally twice daily for 90 days. | Drug: Placebo<br>* Placebo matched to basmisanil immediate-release granules will be given orally twice daily for 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FMMS Score at Day 90 |  | Baseline (Day 1), Day 90 | 
| Number of Participants with Adverse Events |  | Baseline (Day 1) up to 28 days after last dose of study drug (latest at Day 118) | 
| Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Day 30 |  | Baseline (Day 1), Day 30 | 
| Change From Baseline in MoCA Score at Day 90 |  | Baseline (Day 1), Day 90 | 
| Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score At Day 3 |  | Baseline (Day 1), Day 3 | 
| Change From Baseline in NIHSS Score At Day 10 |  | Baseline (Day 1), Day 10 | 
| Change From Baseline in NIHSS Score At Day 30 |  | Baseline (Day 1), Day 30 | 
| Change From Baseline in NIHSS Score At Day 90 |  | Baseline (Day 1), Day 90 | 
| Change From Baseline in NIHSS Score At 28 Days After Last Dose |  | Baseline (Day 1) and at 28 days after last dose of study drug (latest on Day 118) | 
| Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score At Day 3 |  | Baseline (Day 1), Day 3 | 
| Change From Baseline in C-SSRS Score At Day 30 |  | Baseline (Day 1), Day 30 | 
| Change From Baseline in C-SSRS Score At Day 60 |  | Baseline (Day 1), Day 60 | 
| Change From Baseline in C-SSRS Score At Day 90 |  | Baseline (Day 1), Day 90 | 
| Change From Baseline in C-SSRS Score At 28 Days After Last Dose |  | Baseline (Day 1), at 28 days after last dose of study drug (latest on Day 118) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified Rankin Scale (mRS) Score At Day 90 |  | Baseline (Day 1), Day 90 | 
| mRS Score At Day 90 |  | Day 90 | 
| Change From Baseline in Fugl-Meyer Assessment (FMA) Total Score at Day 90 |  | Baseline (Day 1), Day 90 | 
| Change From Baseline in FMA Subscale Score at Day 90 |  | Baseline (Day 1), Day 90 | 
| Apparent Oral Clearance (CL/F) of Basmisanil |  | Predose (Hour 0) (prior to morning dose) on Days 3, 10, 30, 90; 4 and 8 hours post-morning dose on Day 1; and 4 hours post-morning dose on Day 3 | 
| Maximum Observed Plasma Concentration (Cmax) of Basmisanil |  | Predose (Hour 0) (prior to morning dose) on Days 3, 10, 30, 90; 4 and 8 hours post-morning dose on Day 1; and 4 hours post-morning dose on Day 3 | 
| Apparent Volume of Distribution at Steady States (Vss) of Basmisanil |  | Predose (Hour 0) (prior to morning dose) on Days 3, 10, 30, 90; 4 and 8 hours post-morning dose on Day 1; and 4 hours post-morning dose on Day 3 | 
| Area Under the Curve [AUC] of Basmisanil |  | Predose (Hour 0) (prior to morning dose) on Days 3, 10, 30, 90; 4 and 8 hours post-morning dose on Day 1; and 4 hours post-morning dose on Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Motor impairment, Stroke recovery, Middle cerebral artery stroke, Fugl Meyer, Fugl-Meyer Motor Scale (FMMS)