Stroke Motor Recovery MedDRA version: 19.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Basmisanil
Product Code: Ro 518-6582/F15
Pharmaceutical Form: Granules
INN or Proposed INN: basmisanil
CAS Number: 1159600-41-5
Current Sponsor code: RO5186582
Other descriptive name: RO
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Aged 50-80 years - Radiologic assessment confirming an acute middle cerebral artery ischaemic stroke - Index stroke occurred within the past 3-4 days - Availability of brain images and interpretation, medications, blood pressure and blood glucose values from admission until screening for study file - Inpatient males and females; females must be either surgically sterile (by means of hysterectomy, and/or bilateral oophorectomy) or post-menopausal for at least one year (i.e., continuous amenorrhea) and not receiving oestrogen therapies - Severe hemiparesis or hemiplegia defined by FMMS score =65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: Neurological and Psychiatric Assessments and Conditions: - National Institute of Health Stroke Scale (NIHSS) > 20 - Severe aphasia that prevents a patient from adequately completing study assessments and following directions in rehabilitation - Significant deficit from prior strokes or pre-existing motor deficit (mRS >= 2 prior to index stroke) - Received upper and/or lower extremity botulinum toxin within 6 months - History of epilepsy, neurosurgery, severe head trauma or central nervous system infections (e.g., meningitis) 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 (e.g., requiring hospitalization, alcohol and/or substance use disorder) within 12 months prior to stroke - History of suicidal behaviour or otherwise considered a high suicidal risk by the Investigator Cardiovascular Assessments and Conditions: - Due to undergo carotid surgery within the next 4 months - Medical history of clinical symptoms of heart failure or coronary artery disease exceeding New York Heart Association Class II - Severe or treatment-refractory hypotension, hypertension or hyperglycaemia from the immediate post stroke period through screening - Repeat heart rate below 50 beats per minute (bpm) or above 100 bpm - Repeat systolic blood pressure above 180 millimetre of mercury (mmHg) or diastolic above 110 mmHg (corresponding to Grade 3 = severe hypertension) - Repeat systolic blood pressure below 80 mmHg or diastolic below 40 mmHg - Electrocardiogram (ECG) abnormalities at screening. Atrial fibrillation is allowed Investigational and Concomitant Medication: - 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) - Known hypersensitivity to the excipients of the study drug - Concomitant use of prohibited medications Other Medical Assessments and Conditions: - Clinically relevant medical conditions, e.g., immunological, pulmonary, hepatic, or renal dysfunction, that according to the judgment of the Investigator would likely interfere with the study conduct and scheduled assessments - History of malignancy if not considered cured or stabilized according to the judgment of the Investigator (i.e., unlikely to affect patient’s performance throughout the next 4 months) - Donation or loss of blood over 500 millilitre within 3 months prior to randomization - Evidence of acute infections not considered controlled by anti-infectives - Clinically significant abnormality in clinical chemistry parameters at the time of screening, including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN); total bilirubin > ULN with the exception of Gilbert syndrome; glycosylated haemoglobin A1c > 9%; serum creatinine exceeding 1.5-fold ULN - Serology positive for human immunodeficiency virus infection, Hepatitis B or Hepatitis C Magnetic resonance imaging (MRI)-related Exclusion Criteria: - Contraindication to MRI (e.g., artificial heart valves, pacemakers, ear implants, foreign metal objects in the eyes, skin or body, etc.) or conditions which render interpret
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives for this study are: • To evaluate the efficacy of 90-day compliant basmisanil treatment on motor recovery in adult patients with severe motor impairment following an ischemic stroke, as measured by change from baseline on the Fugl-Meyer Motor Scale (FMMS). • To evaluate the tolerability and safety of basmisanil in ischemic stroke patients.;Secondary Objective: The secondary objectives for this study are: •To evaluate the effect of 90-day treatment of basmisanil relative to placebo on functional improvement, as measured by modified Rankin scale (mRS) at Day 90 •To evaluate the effect of 90-day treatment of basmisanil relative to placebo on change from baseline in mRS •To evaluate the effect of 90-day treatment of basmisanil relative to placebo on change from baseline in motor and sensory function, as measured by the Fugl-Meyer Assessment (FMA) total and subscales •To evaluate the pharmacokinetics (PK) of basmisanil and its metabolite(s) •To explore the exposure-response relationships in patients using a population analysis approach;Primary end point(s): 1. Change from baseline in FMMS to Day 90 2. Incidence of adverse events 3. Incidence of vital sign, ECG, or laboratory abnormalities 4. Changes in infarct lesion volume as determined by MRI 5. Incidence of abnormal changes in electroencephalography (EEG) recordings as compared to baseline measurements 6. Changes from baseline in the NIHSS 7. Changes from baseline in the Montreal Cognitive Assessment (MoCA) 8. Columbia-Suicide Severity Rating Scale (C-SSRS);Timepoint(s) of evaluation of this end point: 1. Baseline (Day 1) to Day 90 2-3. Up to Day 118 4. Baseline, Day 3, and Day 90 5. Baseline, Day 3, Day 30, and Day 90 6. Baseline to Day 118 7. Baseline to Day 90 8. Screening (Day -3), Baseline, Day 3, Day 30, Day 60, Day 90, and Day 118 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. mRS at Day 90 2. Change from baseline in mRS to Day 90 3. Apparent clearances and volumes 4. Area under the curve (AUC) 5. Maximum plasma concentration (Cmax);Timepoint(s) of evaluation of this end point: 1. Day 90 2. Baseline to Day 90 3-5. Day 1 (post-dose); predose on Day 3, Day 10, Day 30, and Day 90 | — |
Countries
Spain
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed