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

Terminated

Phase 2 Results N/A

Trial Description

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.

Conditions

Interventions

  • Piclozotan Drug
    Intervention Desc: A selective and potent partial agonist of 5HT1A, has been shown to be neuroprotective against ischemic neuronal damage in animal models. Its pharmacokinetics, tolerability and safety have been evaluated in patients with acute ischemic stroke.
  • Placebo Drug
    Intervention Desc: Continuous IV infusion over a period of up to 72 hours of placebo.
    ARM 1: Kind: Experimental
    Label: 3
    Description: placebo (normal saline) IV infusion, for 72 hours.
  • Piclozotan low dose Drug
    Intervention Desc: Continuous IV infusion over a period of up to 72 hours of piclozotan
    ARM 1: Kind: Experimental
    Label: 1
    Description: piclozotan IV infusion, low dose, for 72 hours.
  • Piclozotan high dose Drug
    Intervention Desc: Continuous IV infusion over a period of up to 72 hours of piclozotan
    ARM 1: Kind: Experimental
    Label: 2
    Description: piclozotan IV infusion, high dose, for 72 hours.
  • Piclozotan high dose Drug
    Intervention Desc: Continuous IV infusion over a period of up to 72 hours of piclozotan
    ARM 1: Kind: Experimental
    Label: 2
    Description: piclozotan IV infusion, high dose, for 72 hours.

Trial Design

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

Patient Involvement

Eligible subjects will be randomized to one of three dose groups; placebo, 80 or 120 ng/mL of study medication.

The study is being conducted in 2 stages. Stage 1 is assessing the efficacy of 2 dose levels of piclozotan vs placebo. If predetermined efficacy (vs placebo) and safety criteria are met, the piclozotan dose with more responses (patients with no growth in stroke lesion volume [SLV]) will be deemed the “winning dose” and the trial will continue to Stage 2, with randomization of more patients to this dose or placebo.

Outcomes

Type Measure Time Frame Safety Issue
Primary Change in stroke lesion volume from Screening to Day 28, clinical outcomes at Day 28 and 90 (Modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale [NIHSS]).
Secondary All-cause-mortality at day 28 and 90.
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

Sponsors