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.

• Conditions: Treatment of acute stroke.

• Registration Number: EUCTR2004-002437-39-BE
• Lead Sponsor: Daiichi Asubio Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-23
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 206

Inclusion Criteria

General Inclusion Criteria
1.Males or females >= 18 and <= 85 years of age at randomization. Female subjects must be either:
- Surgically sterile
- Post-menopausal for at least 1 year
- Non pregnant confirmed by serum pregnancy test, and using a method
of birth control that is acceptable to the investigator.
2.Neurological examination demonstrating localizing cortical signs
3.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)
4.Signed informed consent from subject or a legally acceptable representative
5.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
1.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.)
2.DWI with the longest diameter in any plane of at least 2 cm and no longer than 8 cm
3.PWI with the longest diameter in any plane of at least 3 cm
4.Screening PWI abnormality exceeding the Screening DWI abnormality (mismatch) by 50% in volume or > 1 cm in diameter

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

General Exclusion Criteria:
1.Two or more of the following:
a.Reduced level of consciousness (score ? 2 on NIHSS Q1a)
b.Forced eye deviation or total gaze paresis (score of 2 on NIHSS Q2)
c.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)
2.Pre-stroke Modified Rankin score ? 2 at Screening
3.Rapid neurological improvement from Screening up to the start of drug infusion
4.Persistent systolic blood pressure (SBP) > 220 mmHg and/or diastolic blood pressure (DSP) > 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, the subject may be enrolled.
5.Aggressive anti-hypertensive therapy required to maintain blood pressure at acceptable levels
6.Female subjects who are pregnant and/or nursing, confirmed by serum pregnancy test
7.Administration of an investigational product within the past 30 days
8.Currently taking any selective serotonin reuptake inhibitor (SSRI) and/or other medications listed in Section 9.9 and Attachment II of the protocol
9.Significant renal dysfunction as defined by a serum creatinine > 2.5 mg/dL and a creatinine clearance < 30 mL/min based on Cockroft-Gault formula
10.Significant hepatic disease as defined by liver function tests (LFT) ? 3 times the upper limit of normal
11.Seizure during the current stroke episode
12.Received, or is a candidate to receive, thrombolytics for the current stroke episode
13.Life expectancy of less than 90 days
14.Another significant neurologic disease or previous stroke in addition to the current stroke that would, in the opinion of the Investigator, interfere with the neurological assessment
15.Myocardial infarction within 3 months of study entry
16.Unstable angina pectoris
17.Congestive heart failure with symptoms either at rest or minimal exertion (New York Heart Association [NYHA] Class III or IV)
18.Cardiac conduction system abnormality including second or third degree atrioventricular (AV) block
19.Sinus bradycardia (resting heart rate< 50 beats per minute) or a history of sick sinus syndrome
20.Evidence of QTc prolongation (>450 milliseconds) on Screening ECG
21.Known history of symptomatic orthostatic hypotension
22.Persistent elevation of glucose > 300 mg/dL during screening
23.Cancer under active treatment
24.Received known cytochrome P450 3A4 inhibitors including azole antifungal agents (e.g., ketoconazole, itraconazole) within 24 hours prior to Hour 0 and for 3 days after Hour 72. An appropriate longer washout period is required for drugs with a longer half-life.

MRI-Determined Exclusion Criteria
1.Intracranial hemorrhage as verified by the Screening MRI (or a computerized tomography [CT] scan performed pre-screening)
2.Subacute stroke in a symptomatic region of the brain verified by significant T2 shine through on the Screening FLAIR MRI
3.Significant mass effect, edema, or midline shift including Screening DWI abnormality greater than 2/3 of the MCA territory
4.DWI longest diameter greater than 8 cm or less than 2 cm
5.No Screening PWI abnormality and therefore no PWI/DWI mismatch
6.Contraindication to MRI (ferrous implants, cardiac pacemakers, claustrophobia, or known sensitivity to MRI contrast agents)
7.Severe agitation that precludes MRI

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified