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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00272909

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: piclozotan low dose Drug: placebo Drug: piclozotan high dose	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2004

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 piclozotan IV infusion, low dose, for 72 hours.	Drug: piclozotan low dose Continuous IV infusion over a period of up to 72 hours of piclozotan
Experimental: 2 piclozotan IV infusion, high dose, for 72 hours.	Drug: piclozotan high dose Continuous IV infusion over a period of up to 72 hours of piclozotan
Placebo Comparator: 3 placebo (normal saline) IV infusion, for 72 hours.	Drug: placebo Continuous IV infusion over a period of up to 72 hours of placebo.

Arm

Intervention/Treatment

Experimental: 1

piclozotan IV infusion, low dose, for 72 hours.

Drug: piclozotan low dose

Continuous IV infusion over a period of up to 72 hours of piclozotan

Experimental: 2

piclozotan IV infusion, high dose, for 72 hours.

Drug: piclozotan high dose

Continuous IV infusion over a period of up to 72 hours of piclozotan

Placebo Comparator: 3

placebo (normal saline) IV infusion, for 72 hours.

Drug: placebo

Continuous IV infusion over a period of up to 72 hours of placebo.

Outcome Measures

Primary Outcome Measures

Improvement in MRI [28 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Stroke Network	Los Angeles	California	United States	90024
2	San Francisco Clinical Research Center	San Francisco	California	United States	94109
3	The Stroke Center at Hartford Hospital	Hartford	Connecticut	United States	06102
4	Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
5	OCALA Neurodiagnostic Center	Ocala	Florida	United States	34471
6	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
7	Ruan Neurology Clinic and Clinical Research Center	Des Moines	Iowa	United States	50314
8	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
9	University of Kentucky, Sanders Brown Center on Aging/Stroke Program	Lexington	Kentucky	United States	40536
10	University of Massachusetts, Memorial Health Center, Department of Neurology	Worcester	Massachusetts	United States	01655
11	Wayne State University	Detroit	Michigan	United States	48201
12	Michigan State University, Sparrow Health System	East Lansing	Michigan	United States	48824
13	St. Luke's Hospital	Kansas City	Missouri	United States	64111
14	Advance Neurology Specialists	Great Falls	Montana	United States	59405
15	St. Francis Medical Center	Trenton	New Jersey	United States	08629
16	SUNY at Stony Brook, University Hospital at Stony Brook	Stony Brook	New York	United States	11794
17	Moses Cone Hospital	Greensboro	North Carolina	United States	27401
18	Clinical Research Center of Winston-Salem	Winston-Salem	North Carolina	United States	27103
19	Summa Health System Neurology and Neuroscience Associates	Akron	Ohio	United States	44309
20	Chattanooga Neurology Associates	Chattanooga	Tennessee	United States	37404
21	Methodist University Hospital	Memphis	Tennessee	United States	38104
22	The Methodist Hospital Neurological Institute	Houston	Texas	United States	77030
23	INOVA Research Center	Falls Church	Virginia	United States	22042
24	Charleston Area Medical Center Health Education and Research Institute	Charleston	West Virginia	United States	25304
25	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
26	General Hospital Middelheim, Dept. of Neurology	Antwerp		Belgium	2020
27	Hopital Erasme - Dept. of Neurology, Universite Libre de Bruxelles	Brussels		Belgium	B-1070
28	Uz Gasthuisberg, Neurology	Leuven		Belgium	3000
29	Universitatsklinikum Essen, Department of Neurology	Essen		Germany	D-45147
30	Neurologische Universitatsklinik und Poliklinik - Neurzentrum	Freiburg		Germany	79106
31	Universitatsklinikum Leipzig Aor, Klinik And Poliklinok Fur Neurologie	Leipzig		Germany	04103
32	Neurologische Klinik, Klinikum Rechts Der Isar Der Tu Munchen	Munchen		Germany	81675
33	Soroka University Medical Center	Beer-Sheva		Israel	84101
34	Rambam Medical Center	Haifa		Israel	31096
35	Hadassah University Hospital	Jerusalem		Israel	91120
36	Chaim Sheba Medical Center	Tel Hashomer		Israel	52621
37	Tel-Aviv Sourasky Medical Center	Tel-Aviv		Israel	64239
38	Assaf Harofeh Medical Center	Zrifin		Israel	70300
39	Centralny Szpital Kliniczny	Katowice		Poland	40-752
40	Collegium Medicum Jegiellonian University	Krakow		Poland	31-503
41	Military Institute of Medicine	Warsaw		Poland	00-909
42	St Augustines Hospital	Durban		South Africa	4001
43	Vergelegen Medi-Clinic	Somerset West		South Africa	7130
44	Sunninghill Hospital Cnr.	Sunninghill		South Africa	2157
45	Hospital Universitari Germans Trias i Pujol	Barcelona		Spain	08916
46	University Hospital of Girona Dr. Josep Trueta, Neurology Department	Girona		Spain	17007
47	Hospitales Universitarios Virgen Del Rocio	Sevilla		Spain	41013