A Phase Ib/II in Patients With Acute Ischemic Stroke
Condition: Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia
Intervention: 0.05 mL/kg DDFPe; 0.05 mL/kg Placebo; 0.10 mL/kg DDFPe; 0.10 mL/kg Placebo; 0.17 mL/kg DDFPe; 0.17 mL/kg Placebo
Intervention description: Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.05 mL/kg based on patient body weight in kilograms (kg).; Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.05 mL/kg is based on patient body weight in kilograms (kg).; Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.10 mL/kg based on patient body weight in kilograms (kg).; Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.10 mL/kg is based on patient body weight in kilograms (kg).; Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.17 mL/kg based on patient body weight in kilograms (kg).; Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.17 mL/kg is based on patient body weight in kilograms (kg).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      Stroke is the fifth leading cause of death in the United States and is the leading cause of
      long term disability. Distinct geographic disparities in stroke mortality, with highest rates
      in the southeast United States including Arkansas, are known as the "stroke belt." There the
      average stroke mortality is ≈20% to 40% higher than the rest of the nation. Stroke is the
      leading cause of serious long-term disability. Between 2012 and 2030, disability and medical
      costs related to stroke are projected to triple, from $71.6 billion to $184.1 billion, with
      the majority of the projected increase in costs arising from those 65 to 79 years of age.

      There are two main forms of stroke, ischemic and hemorrhagic. An ischemic stroke occurs in
      85% of cases and is caused by cerebral vessel occlusion, obstructing blood flow to a portion
      of the brain. Currently, the only approved therapies for acute ischemic stroke are IV tissue
      plasminogen activator (tPA), a thrombolytic agent that clears the thrombus within the blood
      vessel, or intra-arterial catheter thrombectomy. Despite the availability of therapy, it
      reaches only approximately 7% of ischemic stroke victims in the United States5. Delay beyond
      the effective time window for therapy is a common reason for failure.

      To reduce the devastating impact of stroke on individuals and society, the investigators
      continue to seek ways to improve functional recovery and limit ischemic damage in stroke
      patients. The potential neuroprotective agent, dodecafluoropentane emulsion (DDFPe) has
      recently shown strong positive effects in pre-clinical animal models of acute ischemic
      stroke6-11. Other perfluorocarbons have been tested in humans as potential neuroprotectants
      and blood substitutes yet none have been successful.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages 18-80 years

          -  Diagnosis of AIS

          -  Body weight ≥ 45 kg

          -  NIHSS between 2 and 20

          -  Patient or legal authorized representative (LAR) must be willing and able to
             understand the study and provide written informed consent

        Exclusion Criteria:

        Currently pregnant or breastfeeding

          -  History of significantly impaired renal or hepatic function

          -  Hemorrhage or hemorrhagic stroke on CT scan

          -  Prior stroke, intracranial surgery, or major head trauma within three months prior to
             enrollment

          -  Pre-stroke modified Rankin Scale (mRS) ≥ 2

          -  Myocardial infarction within six (6) months prior to enrollment

          -  Unstable angina, New York Heart Association (NYHA) Class II or greater congestive
             heart failure

          -  Uncontrolled hypertension (SBP > 180 and/or diastolic blood pressure (DBP) > 110 mmHg)

          -  Known long QT syndrome or QTc > 450 milliseconds (ms) in males and > 470 ms in females

          -  Uncontrolled arrhythmia or history of clinically significant arrhythmia within the
             past six (6) months (except atrial fibrillation)

          -  Clinically significant chronic obstructive pulmonary disease (COPD) or other pulmonary
             condition that is not controlled by medication or requires oxygen frequently or
             continuously

          -  Pneumonia, bronchitis, or other acute respiratory disease

          -  Current anticoagulant therapy except for antiplatelet therapy (aspirin, NSAIDs) and
             prophylactic doses of low molecular weight heparin to prevent deep vein thrombosis.
             Note: tPA administered as part of subjects' therapy for AIS is allowed.

          -  History of allergic reaction attributed to compounds of similar chemical composition
             to DDFPe (see Investigator's Brochure).

          -  Subject has received any investigational drug within thirty (30) days prior to
             enrollment into the study

          -  Inability to comply with the study procedures

          -  History or evidence of any other clinically significant condition that, in the opinion
             of the investigator, might pose a safety risk to subjects or interfere with study
             procedures, evaluation, or completion