Acute Ischemic Stroke (AIS)
Conditions
Brief summary
The objectives of this study are to assess the safety, tolerability and local tolerance, and to investigate the plasma levels and terminal elimination half life of MCI-186, and to review the routine clinical and neurological assessments data of MCI-186 in subjects with acute ischemic stroke.
Interventions
DRUGMCI-186
Cohort 1: Edaravone: circa 1000 mg / 72-hour infusion Cohort 2: Edaravone: circa 2000 mg / 72-hour infusion
DRUGPlacebo
Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Full functional independence prior to the present stroke (as evidenced by a pre-morbid modified Rankin Scale score of 0-2 * Clinical diagnosis of acute stroke with CT scan ruling out intracranial hemorrhage * Onset of symptoms within 1-24 hours of commencement of infusion of study drug * Measurable deficit on NIHSS (as evidenced by a score of 3-15) * Full consciousness (i.e. the score for NIHSS item 1a=0) * Written valid informed consent is obtained from the subject or his/her next of kin or legal representative if the subject is fully conscious (i.e. the score for NIHSS item 1a = 0) but unable to read and/or sign the ICF, in accordance with National legislation and local IRB requirements
Exclusion criteria
* Subjects who are unlikely to complete the infusion of investigational product and/or are unlikely to undergo active medical management during that period due to a severe clinical condition * Subjects with severe illness with life expectancy less than 6 months * Body weight in excess of 120 kg * Subjects who have received rTPA or other thrombolytics (e.g. urokinase, streptokinase, reteplase, tenecteplase) within the previous 24 hours * Likelihood of forbidden concomitant therapy such as vascular surgery, coronary artery bypass graft (CABG), valve replacement, or carotid endarterectomy (CEA) * Evidence of cerebral herniation * Subjects with confounding neurological diseases such as dementia * Subjects with CADASIL, Moya Moya, or carotid dissection * Subjects who have experienced a stroke within the previous 3 months (Note: subjects who have recently experienced a TIA, but whose premorbid mRS prior to their stroke is 0-2, will be allowed to enter the study) * Evidence from admission imaging tests of infarction involving \>1/3 of MCA territory, or entire ACA territory involvement, or internal carotid artery (ICA) occlusions without coexisting separate occlusion of the middle cerebral artery (because of the difficulty distinguishing between chronic and acute ICA lesions in such subjects) * Pathology other than cerebral infarction on any admission imaging tests (e.g. ICH or SAH, AV malformation, cerebral aneurysm, or cerebral neoplasm) * Current or previous known excessive alcohol use or dependence * Current known illicit drug use or dependence * Participation in a previous clinical study within 30 days * Subjects unlikely to be able and willing to attend all study follow-up visits * Any other conditions which in the opinion of the investigator deem the subject ineligible for inclusion * Females who are pregnant or intend to become pregnant or subjects (male and female) who do not agree to use effective contraception for 3 months after end of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Experienced Adverse Events | 87days | Additional Outcome Measures are included in Tables for Serious Adverse Events and Other Adverse Events to report their numbers and frequency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma MCI-186 Pharmacokinetics | 72 hours | The geometric mean values of MCI-186 plasma concentration at the end of the infusion (at 72h) in cohorts 1 and 2 were determined. |
| mRS, NIHSS, Barthel Index | throughout study | — |
Countries
Finland, Netherlands, United Kingdom
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-186 Cohort1 Edaravone: circa 1000 mg / 72-hour infusion | 12 |
| MCI-186 Cohort2 Edaravone: circa 2000 mg / 72-hour infusion | 13 |
| Placebo Group Cohort1:circa 1000mg / 72-hour infusion matching placebo
Cohort2:circa 2000mg / 72-hour infusion matching placebo | 11 |
| Total | 36 |
Baseline characteristics
| Characteristic | MCI-186 Cohort1 | MCI-186 Cohort2 | Placebo Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 4 Participants | 9 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 9 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| other Total, other adverse events | 12 / 12 | 10 / 13 | 10 / 11 |
| serious Total, serious adverse events | 0 / 12 | 2 / 13 | 1 / 11 |
Outcome results
Primary
Number of Participants That Experienced Adverse Events
Additional Outcome Measures are included in Tables for Serious Adverse Events and Other Adverse Events to report their numbers and frequency.
Time frame: 87days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 Cohort1 | Number of Participants That Experienced Adverse Events | Serious Adverse Events | 0 participants |
| MCI-186 Cohort1 | Number of Participants That Experienced Adverse Events | Deaths | 0 participants |
| MCI-186 Cohort1 | Number of Participants That Experienced Adverse Events | Other Adverse Events | 12 participants |
| MCI-186 Cohort2 | Number of Participants That Experienced Adverse Events | Serious Adverse Events | 2 participants |
| MCI-186 Cohort2 | Number of Participants That Experienced Adverse Events | Deaths | 0 participants |
| MCI-186 Cohort2 | Number of Participants That Experienced Adverse Events | Other Adverse Events | 10 participants |
| Placebo Group | Number of Participants That Experienced Adverse Events | Deaths | 0 participants |
| Placebo Group | Number of Participants That Experienced Adverse Events | Other Adverse Events | 10 participants |
| Placebo Group | Number of Participants That Experienced Adverse Events | Serious Adverse Events | 1 participants |
Secondary
mRS, NIHSS, Barthel Index
Time frame: throughout study
Secondary
Plasma MCI-186 Pharmacokinetics
The geometric mean values of MCI-186 plasma concentration at the end of the infusion (at 72h) in cohorts 1 and 2 were determined.
Time frame: 72 hours
Population: The subjects with reliable measured values for plasma concentration were selected for pharmacokinetic analysis: 5 subjects in MCI-186 Cohort 1 and 11 subjects in MCI-186 Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 Cohort1 | Plasma MCI-186 Pharmacokinetics | 391 ng / ml | Geometric Coefficient of Variation 24.21 |
| MCI-186 Cohort2 | Plasma MCI-186 Pharmacokinetics | 1595 ng / ml | Geometric Coefficient of Variation 51.57 |