Safety and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00821821
• Collaborator: (none)
• Enrollment: 36
• Locations: 3
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 12
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke (AIS)	Drug: MCI-186; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIa, Multi-centre, Randomised, Double-blind, Placebo Controlled, Clinical Study Investigating the Safety, Tolerability and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MCI-186	Drug: MCI-186; Cohort 1: Edaravone: circa 1000 mg / 72-hour infusion Cohort 2: Edaravone: circa 2000 mg / 72-hour infusion; Other Names: Edaravone
Placebo Comparator: Placebo Group	Drug: Placebo; Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. mRS, NIHSS, Barthel Index [throughout study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Helsinki University Central Hospital	Helsinki		Finland
2	Erasmus Medical Center	Rotterdam		Netherlands
3	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle		United Kingdom

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Chair: Professor, Information at Mitsubishi Pharma Europe

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00821821
• Other Study ID Numbers: MCI-186-E04
• First Posted: Jan 14, 2009
• Last Update Posted: May 12, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Edaravone

Study Results

Participant Flow

Arm/Group Title	MCI-186 Cohort1	MCI-186 Cohort2	Placebo Group
Arm/Group Description	Edaravone: circa 1000 mg / 72-hour infusion	Edaravone: circa 2000 mg / 72-hour infusion	Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo
Period Title: Overall Study
STARTED	12	13	11
COMPLETED	12	13	11
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	MCI-186 Cohort1	MCI-186 Cohort2	Placebo Group	Total
Arm/Group Description	Edaravone: circa 1000 mg / 72-hour infusion	Edaravone: circa 2000 mg / 72-hour infusion	Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo	Total of all reporting groups
Overall Participants	12	13	11	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 41.7%	9 69.2%	2 18.2%	16 44.4%
>=65 years	7 58.3%	4 30.8%	9 81.8%	20 55.6%
Sex: Female, Male (Count of Participants)
Female	2 16.7%	4 30.8%	3 27.3%	9 25%
Male	10 83.3%	9 69.2%	8 72.7%	27 75%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Experienced Adverse Events
Description	Additional Outcome Measures are included in Tables for Serious Adverse Events and Other Adverse Events to report their numbers and frequency.
Time Frame	87days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186 Cohort1	MCI-186 Cohort2	Placebo Group
Arm/Group Description	Edaravone: circa 1000 mg / 72-hour infusion	Edaravone: circa 2000 mg / 72-hour infusion	Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo
Measure Participants	12	13	11
Deaths	0 0%	0 0%	0 0%
Serious Adverse Events	0 0%	2 15.4%	1 9.1%
Other Adverse Events	12 100%	10 76.9%	10 90.9%

2. Secondary Outcome

Title	Plasma MCI-186 Pharmacokinetics
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	MCI-186 Cohort1	MCI-186 Cohort2
Arm/Group Description	Edaravone:circa 1000mg / 72-hour infusion	Edaravone:circa 2000mg / 72-hour infusion
Measure Participants	5	11
Geometric Mean (Geometric Coefficient of Variation) [ng / ml]	391 (24.21)	1595 (51.57)

3. Secondary Outcome

Title	mRS, NIHSS, Barthel Index
Time Frame	throughout study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	87 days
Arm/Group Title	MCI-186 Cohort1		MCI-186 Cohort2		Placebo Group
Arm/Group Description	Edaravone: circa 1000mg / 72-hour infusion		Edaravone: circa 2000mg / 72-hour infusion		Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo
All Cause Mortality
	MCI-186 Cohort1		MCI-186 Cohort2		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MCI-186 Cohort1		MCI-186 Cohort2		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		2/13 (15.4%)		1/11 (9.1%)
Metabolism and nutrition disorders
Gout	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Nervous system disorders
Hemiparesis	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Ischaemic Stroke	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	MCI-186 Cohort1		MCI-186 Cohort2		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		10/13 (76.9%)		10/11 (90.9%)
Cardiac disorders
Atrial Fibrillation	0/12 (0%)		2/13 (15.4%)		0/11 (0%)
Bradycardia	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Eye disorders
Cataract	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Vision Blurred	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Abdominal Pain Lower	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Constipation	1/12 (8.3%)		0/13 (0%)		2/11 (18.2%)
Diarrhoea	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Dyspepsia	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Gastrooesophageal Reflux Disease	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Mouth Ulceration	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Nausea	5/12 (41.7%)		1/13 (7.7%)		2/11 (18.2%)
Vomiting	1/12 (8.3%)		0/13 (0%)		1/11 (9.1%)
General disorders
Fatigue	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Infusion Site Phlebitis	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Oedema Peripheral	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Pyrexia	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Vessel Puncture Site Haematoma	1/12 (8.3%)		0/13 (0%)		1/11 (9.1%)
Infections and infestations
Eczema Infected	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Groin Abscess	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Infusion Site Infection	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Pneumonia	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Sinusitis	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Urinary Tract Infection	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Investigations
Blood Alkaline Phosphatase Increased	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Blood Creatine Phosphokinase Increased	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Blood Glucose Increased	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Blood Uric Acid Increased	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
C-Reactive Protein Increased	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Gamma-Glutamyltransferase Increased	1/12 (8.3%)		0/13 (0%)		1/11 (9.1%)
Hepatic Enzyme Increased	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Liver Function Test Abnormal	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Metabolism and nutrition disorders
Diabetes Mellitus	1/12 (8.3%)		1/13 (7.7%)		0/11 (0%)
Hypercholesterolaemia	0/12 (0%)		0/13 (0%)		2/11 (18.2%)
Hyperglycaemia	0/12 (0%)		2/13 (15.4%)		0/11 (0%)
Hyperlipidaemia	2/12 (16.7%)		0/13 (0%)		0/11 (0%)
Hyponatraemia	1/12 (8.3%)		1/13 (7.7%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/12 (8.3%)		1/13 (7.7%)		0/11 (0%)
Muscle Spasms	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Myalgia	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Osteoarthritis	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Nervous system disorders
Cerebrovascular Accident	1/12 (8.3%)		0/13 (0%)		1/11 (9.1%)
Dizziness	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Headache	4/12 (33.3%)		4/13 (30.8%)		4/11 (36.4%)
Hypoaesthesia	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Neuralgia	1/12 (8.3%)		1/13 (7.7%)		0/11 (0%)
Paraesthesia	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Simple Partial Seizures	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Somnolence	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Speech Disorder	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Transient Ischaemic Attack	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Psychiatric disorders
Anxiety	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Depression	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Insomnia	1/12 (8.3%)		0/13 (0%)		0/11 (0%)
Renal and urinary disorders
Urethral Haemorrhage	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Urinary Incontinence	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Pleural Fibrosis	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Pulmonary Oedema	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/12 (0%)		0/13 (0%)		1/11 (9.1%)
Rash	1/12 (8.3%)		0/13 (0%)		1/11 (9.1%)
Stasis Dermatitis	0/12 (0%)		1/13 (7.7%)		0/11 (0%)
Vascular disorders
Hypertension	3/12 (25%)		2/13 (15.4%)		4/11 (36.4%)
Hypotension	0/12 (0%)		1/13 (7.7%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.