Efficacy of SUN N4057 in Subjects With Acute Ischemic Stroke and Measurable Penumbra on Magnetic Resonance Imaging (MRI)
- Conditions
- Stroke
- Interventions
- Registration Number
- NCT00272909
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
This research study is designed to evaluate the safety, tolerability, and efficacy of SUN N4057 (piclozotan) in subjects with acute ischemic stroke within 9 hours of the onset of symptoms.
- Detailed Description
The primary objective of the study is to determine the efficacy of a 72 hour infusion of SUN N4057 (piclozotan) in subjects with clinical findings of an acute ischemic stroke and a magnetic resonance imaging (MRI) demonstrating a measurable penumbra (perfusion-weighted imaging \[PWI\] minus diffusion-weighted imaging \[DWI\] volume). Efficacy will be determined by comparing the proportion of subjects with no growth in stroke lesion volume as assessed by DWI at Screening to stroke lesion volume assessed by FLAIR (fluid-attenuated inversion recovery) on Day 28 in the piclozotan group versus the placebo group.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 43
General inclusion criteria:
-
Males or females >= 18 and <= 85 years of age at randomization. Female subjects must be either:
- Surgically sterile;
- Postmenopausal for at least 1 year; or
- Non-pregnant, confirmed by a serum pregnancy test, and using a method of birth control that is acceptable to the investigator.
-
Neurological examination demonstrating localizing cortical signs
-
Receipt of study drug less than 6 hours (50% of subjects) or between 6 and 9 hours, inclusive, (50% of subjects) after the onset of symptoms (for un-witnessed stroke, last time seen in normal state or at bedtime for un-witnessed stroke during sleep)
-
Signed informed consent from subject or legally acceptable representative
-
NIHSS score of 6 - 22, inclusive, or at least 2 on the aphasia item of the NIHSS with a location of MRI findings consistent with aphasia
MRI-determined inclusion criteria:
- Acute ischemic stroke with substantial cortical involvement in the middle cerebral artery (MCA) distribution, as verified by the Screening DWI abnormality and/or Screening PWI abnormality. (Note: white matter involvement, in addition to cortex, is not an exclusion.)
General exclusion criteria:
-
Two or more of the following:
- Reduced level of consciousness (score >= 2 on NIHSS Q1a)
- Forced eye deviation or total gaze paresis (score of 2 on NIHSS Q2)
- Dense hemiplegia (no movement) of upper and lower extremities (score of 4 on NIHSS Q5 regarding motor arm and a score of 4 on NIHSS Q6 regarding motor leg)
-
Pre-stroke modified Rankin score >= 2 at Screening
-
Rapid neurological improvement from Screening up to the start of drug infusion
-
Persistent systolic blood pressure (SBP) > 220 mmHg and/or diastolic blood pressure (DBP) > 120 mmHg (confirmed by at least three readings taken at least 3 minutes apart) prior to randomization. If subsequent readings are consistently below these levels, either spontaneously or following mild antihypertensive therapy, subject may be enrolled.
MRI-determined exclusion criteria:
- Intracranial hemorrhage as verified by Screening MRI. (Note: intracranial hemorrhage on pre-screen computerized tomography [CT] scan also excludes subject.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 piclozotan high dose piclozotan IV infusion, high dose, for 72 hours. 1 piclozotan low dose piclozotan IV infusion, low dose, for 72 hours. 3 placebo placebo (normal saline) IV infusion, for 72 hours.
- Primary Outcome Measures
Name Time Method Improvement in MRI 28 days
- Secondary Outcome Measures
Name Time Method The change in stroke lesion volume from Screening to day 28 28 days Clinical outcomes at Days 28 and 90 using the individual clinical scales (Modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale [NIHSS]). Days 28 and 90 To assess the safety and tolerability of SUN N4057 (piclozotan) in subjects with acute stroke. Days 28, 60 and 90
Trial Locations
- Locations (47)
The Stroke Center at Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Chattanooga Neurology Associates
🇺🇸Chattanooga, Tennessee, United States
Lakeland Regional Medical Center
🇺🇸Lakeland, Florida, United States
University of Massachusetts, Memorial Health Center, Department of Neurology
🇺🇸Worcester, Massachusetts, United States
University of Kentucky, Sanders Brown Center on Aging/Stroke Program
🇺🇸Lexington, Kentucky, United States
Summa Health System Neurology and Neuroscience Associates
🇺🇸Akron, Ohio, United States
SUNY at Stony Brook, University Hospital at Stony Brook
🇺🇸Stony Brook, New York, United States
INOVA Research Center
🇺🇸Falls Church, Virginia, United States
Charleston Area Medical Center Health Education and Research Institute
🇺🇸Charleston, West Virginia, United States
Neurologische Klinik, Klinikum Rechts Der Isar Der Tu Munchen
🇩🇪Munchen, Germany
Sunninghill Hospital Cnr.
🇿🇦Sunninghill, South Africa
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
University Hospital of Girona Dr. Josep Trueta, Neurology Department
🇪🇸Girona, Spain
Wayne State University
🇺🇸Detroit, Michigan, United States
Centralny Szpital Kliniczny
🇵🇱Katowice, Poland
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Collegium Medicum Jegiellonian University
🇵🇱Krakow, Poland
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Military Institute of Medicine
🇵🇱Warsaw, Poland
Tel-Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
St. Francis Medical Center
🇺🇸Trenton, New Jersey, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
UCLA Stroke Network
🇺🇸Los Angeles, California, United States
Uz Gasthuisberg, Neurology
🇧🇪Leuven, Belgium
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
General Hospital Middelheim, Dept. of Neurology
🇧🇪Antwerp, Belgium
Rambam Medical Center
🇮🇱Haifa, Israel
Advance Neurology Specialists
🇺🇸Great Falls, Montana, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
OCALA Neurodiagnostic Center
🇺🇸Ocala, Florida, United States
Clinical Research Center of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Ruan Neurology Clinic and Clinical Research Center
🇺🇸Des Moines, Iowa, United States
St. Luke's Hospital
🇺🇸Kansas City, Missouri, United States
The Methodist Hospital Neurological Institute
🇺🇸Houston, Texas, United States
Hopital Erasme - Dept. of Neurology, Universite Libre de Bruxelles
🇧🇪Brussels, Belgium
Universitatsklinikum Essen, Department of Neurology
🇩🇪Essen, Germany
Neurologische Universitatsklinik und Poliklinik - Neurzentrum
🇩🇪Freiburg, Germany
Universitatsklinikum Leipzig Aor, Klinik And Poliklinok Fur Neurologie
🇩🇪Leipzig, Germany
St Augustines Hospital
🇿🇦Durban, South Africa
Soroka University Medical Center
🇮🇱Beer-Sheva, Israel
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Assaf Harofeh Medical Center
🇮🇱Zrifin, Israel
Vergelegen Medi-Clinic
🇿🇦Somerset West, South Africa
Hospitales Universitarios Virgen Del Rocio
🇪🇸Sevilla, Spain
Michigan State University, Sparrow Health System
🇺🇸East Lansing, Michigan, United States
Moses Cone Hospital
🇺🇸Greensboro, North Carolina, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States