Efficacy of SUN N4057 in Subjects With Acute Ischemic Stroke and Measurable Penumbra on Magnetic Resonance Imaging (MRI)

Stroke Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00272909
• Other study ID #: SPI-103
• Status: Terminated
• Phase: Phase 2
• First received: January 5, 2006
• Last updated: October 19, 2015
• Start date: September 2004
• Est. completion date: January 2007

Study information

• Verified date: October 2015
• Source: Daiichi Sankyo Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: January 2007
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• piclozotan low dose
Continuous IV infusion over a period of up to 72 hours of piclozotan
• placebo
Continuous IV infusion over a period of up to 72 hours of placebo.
• piclozotan high dose
Continuous IV infusion over a period of up to 72 hours of piclozotan

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Israel,  Poland,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in MRI		28 days	No
Secondary	The change in stroke lesion volume from Screening to day 28		28 days	No
Secondary	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	No
Secondary	To assess the safety and tolerability of SUN N4057 (piclozotan) in subjects with acute stroke.		Days 28, 60 and 90	No