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

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

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.

Study Overview

• Status: Terminated
• Conditions: Stroke
• Intervention / Treatment: Drug: Basmisanil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
  • Bordeaux, France, 33076
    • Hopital Pellegrin Tripode - CHU de Bordeaux
  • Clermont-Ferrand, France, 63003
    • Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
  • Dijon Cedex, France, 21079
    • Hôpital General - Service de neurologie; Service de neurologie
  • Toulouse Cedex 9, France, 31059
    • Hopital Purpan
  • brest Cedex 2, France, 29609
    • Hopital La Cavale Blanche
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Madrid, Spain
    • La Paz University Hospital
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Zaragoza, Spain, 50009
    • Hospital Clnico Universitario de Zaragoza
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2017
• Primary Completion (Actual): November 3, 2017
• Study Completion (Actual): November 3, 2017

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 7, 2016
• First Posted (Estimate): October 10, 2016

Study Record Updates

• Last Update Posted (Actual): January 2, 2019
• Last Update Submitted That Met QC Criteria: December 28, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Stroke; Stroke recovery; Motor impairment; Middle cerebral artery stroke; Fugl Meyer; Fugl-Meyer Motor Scale (FMMS)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: BP29937; 2015-003227-66 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No