Acute Ischemic Stroke
Conditions
Brief summary
To investigate the efficacy and safety of MCI-186 (bolus followed by continuous infusion) in acute ischemic stroke patients through a double-blind, parallel-group comparison with the existing MCI-186 dosing regimen (administration twice daily for 14 days) as the control.
Interventions
DRUGContinuous infusion high-dose MCI-186
intravenous injection
DRUGContinuous infusion low-dose MCI-186
intravenous injection
DRUGContinuous infusion placebo
intravenous injection
DRUGApproved dosing regimen MCI-186
intravenous injection
DRUGApproved dosing regimen placebo
intravenous injection
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients from whom written consent to study participation has been obtained, either from the patient personally or from the patient's legal guardian * Patients with age at consent between 20 and 85 years, inclusive * Patients for whom study treatment can be initiated within 24 hours after onset * Patients with confirmed new ischemic area only in the supratentorial region on MRI * Patients with neurological signs equivalent to between 4 and 22, inclusive, on the NIHSS
Exclusion criteria
* Patients with disability equivalent to an mRS score of 2 or more from before onset * Patients being treated with antibiotics for an infection at registration * Patients who have received or are planning to receive treatment for their primary disease with a prohibited concomitant medication (e.g., a thrombolytic drug) or with a prohibited concomitant therapy (e.g., intravascular therapy) * Patients for whom the (sub)investigator judges the efficacy endpoints (e.g., NIHSS, mRS, BI) that have been selected for this study can not be measured appropriately, such as patients who are not expected to achieve improvement of 4 or more on the NIHSS because of nerve symptoms that have been present since before the onset of cerebral infarction, Alzheimer's dementia patients, or Parkinson's disease patients * Patients with severe consciousness disturbances (Japan coma scale ≥ 100) * Patients with clear concurrent peripheral vascular disease or peripheral neuropathy for whom the (sub)investigator judges the neurological tests could not be performed properly * Patients with severe renal impairment (e.g., patients with eGFR \< 30) * Patients with severe hepatic impairment (e.g., ALT, AST, or gamma-GTP \> 2.5 X ULN) * Patients with platelet count \< 100,000/mm3 * Patients diagnosed by MRI on admission with a disease other than stroke (e.g., intracranial bleeding, subarachnoid bleeding, arteriovenous malformations, Moyamoya disease, brain tumor) or with cerebral aneurysm with a maximum diameter \> 7 mm * Patients with prior or current drug abuse or alcohol dependence * Patients with prior (or current) malignant tumor within 5 years before stroke onset * Patients with a past history of hypersensitivity to edaravone drug products * Patients with concurrent heart disease severe enough to warrant admission and treatment (e.g., acute myocardial infarction, cardiac failure) and with problems with their overall condition judged by the (sub)investigator to be unsuitable for study participation * Patients for whom MRI tests cannot be performed * Male or female patients who do not consent to practice contraception from the date of consent until the day after the administration of the last dose of study drug * Patients who are pregnant or nursing, or who could be pregnant * Patients who have received other investigational drugs in the 12 weeks prior to consent acquisition * Patients with body weight ≥ 100 kg * Patients otherwise judged unsuitable for study participation by the (sub)investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Baseline up to Day 7 | NIHSS is a scale to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40(severe stroke). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of National Institutes of Health Stroke Scale (NIHSS) | Day 14, at discharge(from Day15 to after 3 months) and after 3 months | NIHSS is a scale used to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40 (severe stroke). |
| Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | at discharge(from Day15 to after 3 months) and after 3 months | mRS is a scale for measuring the degree of disability caused by a stroke. Possible scores range from Grade 0 (no symptoms) to Grade 6 (death). Number of Participants with Modified Rankin Scale (mRS) 0-1 are evaluated. |
| Comparison of Barthel Index (BI) | at discharge(from Day15 to after 3 months) and after 3 months | BI is a scale for measuring performance in Activities of Daily Living (ADL). Possible scores range from 0 (worst) to 100 (best). |
| Comparison of Functional Independence Measure (FIM) | at discharge(from Day15 to after 3 months) and after 3 months | FIM is a scale used to evaluate the functional status. Possible scores range from 18 (worst) to 126 (best). |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Continuous Infusion High-dose Group (Group H) High-dose MCI-186 will be administered as a bolus, and then as a continuous infusion. In addition, a placebo will be administered as an intravenous infusion twice a day over 30 minutes. | 7 |
| Continuous Infusion Low-dose Group (Group L) Low-dose MCI-186 will be administered as a bolus, and then as a continuous infusion. In addition, a placebo will be administered as an intravenous infusion twice a day over 30 minutes. | 3 |
| Approved Dosing Regimen Group (Control Group) A placebo will be administered as a bolus, and then as a continuous infusion. In addition, MCI-186 30 mg will be administered as an intravenous infusion twice a day over 30 minutes. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Continuous Infusion High-dose Group (Group H) | Continuous Infusion Low-dose Group (Group L) | Approved Dosing Regimen Group (Control Group) | Total |
|---|---|---|---|---|
| Age, Continuous | 76.3 years STANDARD_DEVIATION 6.8 | 75.7 years STANDARD_DEVIATION 7.4 | 64.4 years STANDARD_DEVIATION 11.2 | 72.2 years STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Japanese | 7 Participants | 3 Participants | 5 Participants | 15 Participants |
| Race/Ethnicity, Customized Non-Japanese | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 6 / 7 | 2 / 3 | 4 / 5 |
| serious Total, serious adverse events | 1 / 7 | 1 / 3 | 1 / 5 |
Outcome results
Primary
Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved.
NIHSS is a scale to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40(severe stroke).
Time frame: Baseline up to Day 7
Population: Among the randomised of 17 subjects, the baseline participants consisted of 15 subjects, excluding 1 who withdrew their consent after randomization and 1 who discontinued prior to initiation of study drug administration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 1 | 0 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 2 | 2 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 3 | 2 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 4 | 2 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 5 | 2 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 6 | 3 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 7 | 3 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 2 | 0 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 6 | 1 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 5 | 0 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 3 | 0 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 4 | 0 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 1 | 0 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 7 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 5 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 2 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 1 | 0 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 6 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 4 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 7 | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With National Institutes of Health Stroke Scale (NIHSS) Score Improved. | Day 3 | 1 Participants |
Secondary
Comparison of Barthel Index (BI)
BI is a scale for measuring performance in Activities of Daily Living (ADL). Possible scores range from 0 (worst) to 100 (best).
Time frame: at discharge(from Day15 to after 3 months) and after 3 months
Population: Among the randomised of 17 subjects, the baseline participants consisted of 15 subjects, excluding 1 who withdrew their consent after randomization and 1 who discontinued prior to initiation of study drug administration. The number of participants decreased at each evaluation point because there was missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continuous Infusion High-dose Group (Group H) | Comparison of Barthel Index (BI) | at discharge | 80 units on a scale | Standard Deviation 36.7 |
| Continuous Infusion High-dose Group (Group H) | Comparison of Barthel Index (BI) | after 3 months | 90 units on a scale | Standard Deviation 17.3 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of Barthel Index (BI) | at discharge | 72.5 units on a scale | Standard Deviation 38.9 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of Barthel Index (BI) | after 3 months | 100 units on a scale | — |
| Approved Dosing Regimen Group (Control Group) | Comparison of Barthel Index (BI) | at discharge | 83.3 units on a scale | Standard Deviation 28.9 |
| Approved Dosing Regimen Group (Control Group) | Comparison of Barthel Index (BI) | after 3 months | 100 units on a scale | Standard Deviation 0 |
Secondary
Comparison of Functional Independence Measure (FIM)
FIM is a scale used to evaluate the functional status. Possible scores range from 18 (worst) to 126 (best).
Time frame: at discharge(from Day15 to after 3 months) and after 3 months
Population: Among the randomised of 17 subjects, the baseline participants consisted of 15 subjects, excluding 1 who withdrew their consent after randomization and 1 who discontinued prior to initiation of study drug administration. The number of participants decreased at each evaluation point because there was missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continuous Infusion High-dose Group (Group H) | Comparison of Functional Independence Measure (FIM) | at discharge | 102.2 units on a scale | Standard Deviation 33.8 |
| Continuous Infusion High-dose Group (Group H) | Comparison of Functional Independence Measure (FIM) | after 3 months | 93.7 units on a scale | Standard Deviation 54.3 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of Functional Independence Measure (FIM) | at discharge | 91.5 units on a scale | Standard Deviation 41.7 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of Functional Independence Measure (FIM) | after 3 months | 125.0 units on a scale | — |
| Approved Dosing Regimen Group (Control Group) | Comparison of Functional Independence Measure (FIM) | after 3 months | 123.4 units on a scale | Standard Deviation 2.5 |
| Approved Dosing Regimen Group (Control Group) | Comparison of Functional Independence Measure (FIM) | at discharge | 121.8 units on a scale | Standard Deviation 4.1 |
Secondary
Comparison of National Institutes of Health Stroke Scale (NIHSS)
NIHSS is a scale used to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40 (severe stroke).
Time frame: Day 14, at discharge(from Day15 to after 3 months) and after 3 months
Population: Among the randomised of 17 subjects, the baseline participants consisted of 15 subjects, excluding 1 who withdrew their consent after randomization and 1 who discontinued prior to initiation of study drug administration. The number of participants decreased at each evaluation point because there was missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continuous Infusion High-dose Group (Group H) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | after 3 months | 3.3 units on a scale | Standard Deviation 3.2 |
| Continuous Infusion High-dose Group (Group H) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | at discharge | 3.5 units on a scale | Standard Deviation 5.1 |
| Continuous Infusion High-dose Group (Group H) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | Day 14 | 3.7 units on a scale | Standard Deviation 6.1 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | after 3 months | 0.0 units on a scale | — |
| Continuous Infusion Low-dose Group (Group L) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | Day 14 | 2.5 units on a scale | Standard Deviation 2.1 |
| Continuous Infusion Low-dose Group (Group L) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | at discharge | 2.0 units on a scale | Standard Deviation 1.4 |
| Approved Dosing Regimen Group (Control Group) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | at discharge | 3.3 units on a scale | Standard Deviation 1.5 |
| Approved Dosing Regimen Group (Control Group) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | Day 14 | 2.8 units on a scale | Standard Deviation 1.5 |
| Approved Dosing Regimen Group (Control Group) | Comparison of National Institutes of Health Stroke Scale (NIHSS) | after 3 months | 1.8 units on a scale | Standard Deviation 0.8 |
Secondary
Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations
mRS is a scale for measuring the degree of disability caused by a stroke. Possible scores range from Grade 0 (no symptoms) to Grade 6 (death). Number of Participants with Modified Rankin Scale (mRS) 0-1 are evaluated.
Time frame: at discharge(from Day15 to after 3 months) and after 3 months
Population: Among the randomised of 17 subjects, the baseline participants consisted of 15 subjects, excluding 1 who withdrew their consent after randomization and 1 who discontinued prior to initiation of study drug administration. The number of participants decreased at each evaluation point because there was missing data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continuous Infusion High-dose Group (Group H) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | at discharge | 4 Participants |
| Continuous Infusion High-dose Group (Group H) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | after 3 months | 2 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | at discharge | 1 Participants |
| Continuous Infusion Low-dose Group (Group L) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | after 3 months | 1 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | at discharge | 3 Participants |
| Approved Dosing Regimen Group (Control Group) | Number of Participants With Modified Rankin Scale (mRS) 0-1 at Each Evaluations | after 3 months | 3 Participants |