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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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
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Stroke

Intervention / Treatment
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* Drug: piclozotan low dose
* Drug: placebo
* Drug: piclozotan high dose


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in MRI |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, 9-Hour window MRI, Serotonin receptor agonist