Clinical trial NCT00272909: Efficacy of SUN N4057 in Subjects With Acute Ischemic Stroke and Measurable Penumbra on Magnetic Resonance Imaging (MRI)
Official title: A Phase IIb Randomized, Double-blind, Placebo-Controlled, Group-Sequential, Multicenter, Dose Finding Study of the Safety and Efficacy of SUN N4057 (Piclozotan) Administered for 72 Hours by Continuous Intravenous Infusion in Subjects With Acute Ischemic Stroke and Measurable Penumbra on MRI
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stroke
Keywords: Acute Ischemic Stroke
9-Hour window MRI
Serotonin receptor agonist
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2006-01-09
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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.)

Exclusion Criteria:

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.)

Primary outcomes:
measure: Improvement in MRI
timeFrame: 28 days
Secondary outcomes:
measure: The change in stroke lesion volume from Screening to day 28
timeFrame: 28 days
measure: 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]).
timeFrame: Days 28 and 90
measure: To assess the safety and tolerability of SUN N4057 (piclozotan) in subjects with acute stroke.
timeFrame: Days 28, 60 and 90
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Stroke Network
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Hartford
country: United States
facility: The Stroke Center at Hartford Hospital
state: Connecticut
city: Lakeland
country: United States
facility: Lakeland Regional Medical Center
state: Florida
city: Ocala
country: United States
facility: OCALA Neurodiagnostic Center
state: Florida
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Des Moines
country: United States
facility: Ruan Neurology Clinic and Clinical Research Center
state: Iowa
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Sanders Brown Center on Aging/Stroke Program
state: Kentucky
city: Worcester
country: United States
facility: University of Massachusetts, Memorial Health Center, Department of Neurology
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University, Sparrow Health System
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Great Falls
country: United States
facility: Advance Neurology Specialists
state: Montana
city: Trenton
country: United States
facility: St. Francis Medical Center
state: New Jersey
city: Stony Brook
country: United States
facility: SUNY at Stony Brook, University Hospital at Stony Brook
state: New York
city: Greensboro
country: United States
facility: Moses Cone Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Research Center of Winston-Salem
state: North Carolina
city: Akron
country: United States
facility: Summa Health System Neurology and Neuroscience Associates
state: Ohio
city: Chattanooga
country: United States
facility: Chattanooga Neurology Associates
state: Tennessee
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Houston
country: United States
facility: The Methodist Hospital Neurological Institute
state: Texas
city: Falls Church
country: United States
facility: INOVA Research Center
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center Health Education and Research Institute
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Antwerp
country: Belgium
facility: General Hospital Middelheim, Dept. of Neurology
city: Brussels
country: Belgium
facility: Hopital Erasme - Dept. of Neurology, Universite Libre de Bruxelles
city: Leuven
country: Belgium
facility: Uz Gasthuisberg, Neurology
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Department of Neurology
city: Freiburg
country: Germany
facility: Neurologische Universitatsklinik und Poliklinik - Neurzentrum
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig Aor, Klinik And Poliklinok Fur Neurologie
city: Munchen
country: Germany
facility: Neurologische Klinik, Klinikum Rechts Der Isar Der Tu Munchen
city: Beer-Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Zrifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Katowice
country: Poland
facility: Centralny Szpital Kliniczny
city: Krakow
country: Poland
facility: Collegium Medicum Jegiellonian University
city: Warsaw
country: Poland
facility: Military Institute of Medicine
city: Durban
country: South Africa
facility: St Augustines Hospital
city: Somerset West
country: South Africa
facility: Vergelegen Medi-Clinic
city: Sunninghill
country: South Africa
facility: Sunninghill Hospital Cnr.
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Girona
country: Spain
facility: University Hospital of Girona Dr. Josep Trueta, Neurology Department
city: Sevilla
country: Spain
facility: Hospitales Universitarios Virgen Del Rocio
Study officials:
References: