Stroke
Conditions
Keywords
Stroke, Motor impairment, Stroke recovery, Middle cerebral artery stroke, Fugl Meyer, Fugl-Meyer Motor Scale (FMMS)
Brief summary
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.
Interventions
DRUGBasmisanil
Basmisanil immediate-release granules at a dose of 240 mg will be given orally twice daily for 90 days.
DRUGPlacebo
Placebo matched to basmisanil immediate-release granules will be given orally twice daily for 90 days.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
| 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 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change From Baseline in Modified Rankin Scale (mRS) Score At Day 90 | Baseline (Day 1), Day 90 |
Countries
France, Spain
Outcome results
None listed