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
Overview
- Phase
- Phase 2
- Intervention
- Basmisanil
- Conditions
- Stroke
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 5
- Locations
- 13
- Primary Endpoint
- Change From Baseline in FMMS Score at Day 90
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Basmisanil
Basmisanil at a dose of 240 milligrams (mg) orally twice daily for 90 days.
Intervention: Basmisanil
Placebo
Placebo matched to basmisanil orally twice daily for 90 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in FMMS Score at Day 90
Time Frame: Baseline (Day 1), Day 90
Number of Participants with Adverse Events
Time Frame: 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
Time Frame: Baseline (Day 1), Day 30
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score At Day 3
Time Frame: Baseline (Day 1), Day 3
Change From Baseline in NIHSS Score At Day 10
Time Frame: Baseline (Day 1), Day 10
Change From Baseline in MoCA Score at Day 90
Time Frame: Baseline (Day 1), Day 90
Change From Baseline in NIHSS Score At Day 30
Time Frame: Baseline (Day 1), Day 30
Change From Baseline in NIHSS Score At Day 90
Time Frame: Baseline (Day 1), Day 90
Change From Baseline in NIHSS Score At 28 Days After Last Dose
Time Frame: 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
Time Frame: Baseline (Day 1), Day 3
Change From Baseline in C-SSRS Score At Day 30
Time Frame: Baseline (Day 1), Day 30
Change From Baseline in C-SSRS Score At Day 60
Time Frame: Baseline (Day 1), Day 60
Change From Baseline in C-SSRS Score At Day 90
Time Frame: Baseline (Day 1), Day 90
Change From Baseline in C-SSRS Score At 28 Days After Last Dose
Time Frame: Baseline (Day 1), at 28 days after last dose of study drug (latest on Day 118)
Secondary Outcomes
- 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)