A Multi-Center, Prospective, Open Label, Phase IIa Trial of RP-1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Experience Clinically Significant Brain Swelling.
Overview
- Phase
- Phase 1
- Intervention
- Glyburide for Injection
- Conditions
- Ischemic Stroke
- Sponsor
- Remedy Pharmaceuticals, Inc.
- Enrollment
- 10
- Locations
- 4
- Primary Endpoint
- Percentage of Participants With All Four MRI Assessments Per Protocol
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The primary objective of this study is to assess the feasibility of enrolling, evaluating, and treating with glyburide for injection severe anterior circulation ischemic stroke participants, whether or not treated with standard of care intravenous (IV) recombinant tissue plasminogen activator (rtPA). Participants must be between 18-80 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 -210 centimeters cubed (cm3), and time from symptom onset to start of study infusion must be ≤10 hour(hr). The secondary objectives are to assess the initial safety and tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of glyburide in severe stroke participants, as well as to compare the clinical and magnetic resonance imaging (MRI) outcome data to benchmark data derived from published literature.
Detailed Description
This is a multi-center, prospective, open label, phase IIa trial of glyburide for injection in 10 participants with a severe anterior circulation ischemic stroke who are likely to experience clinically significant brain swelling. Participants will receive glyburide, delivered as an IV bolus followed by an IV infusion for 72 hours. Participants will have a baseline (pretreatment) MRI scan as standard of care, and three follow up MRI scans (at 24+12 hours, 48+12 hours, and 72±12 hours). Since recanalization may have an effect on outcome, the results of vascular studies, obtained as part of standard of care and defined as CTA, MRA or catheter angiography of the head and neck, will be recorded. Additionally, clinical endpoints such as the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS) and Full Outline of UnResponsiveness Score (FOUR) Score (baseline, 24±12 hour, 48±12 hour, 72±12 hour and 7±1 days) and Modified Rankin Scale (mRS) (30±5 days and 90±7 days) will be assessed. Safety parameters will be assessed through Day 7 or discharge (whichever is sooner), and then again at Day 30±5 and Day 90±7. Study participation is expected to last 90±7 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory.
- •Pre-morbid mRS 0 -
- •A baseline DWI lesion between 82 cm3 and 210 cm3 on MRI.
- •Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods, respectively.
- •The time to the start of infusion of study compound must be ≤ 10 hr after time of symptom onset
- •Age ≥18 years and ≤70 years.
- •Provision of written informed consent by the patient or from a legally authorized representative according to institutional guidelines and national regulations.
Exclusion Criteria
- •Evidence from imaging or pre-enrollment investigation of any diagnosis other than acute ischemic stroke likely to cause the presenting symptoms and signs.
- •Commitment to decompressive craniectomy (DC) prior to enrollment, or follow-ing enrollment and prior to start of study compound.
- •Treatment with IA rtPA or by mechanical means for clot disruption or with hypo-thermia.
- •Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators.
- •Pre-morbid mRS ≥
- •Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); loss of other brain stem reflexes attributable to herniation according to the investigator's judgment.
- •CT or MRI evidence of hemorrhage or anteroseptal/pineal shift greater ≥2 mm prior to enrollment.
- •Rapidly improving symptoms.
- •Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of \< 30 mL/min/1.73 m
- •Severe liver disease or ALT, AST, or bilirubin \>2 times normal.
Arms & Interventions
Glyburide for Injection
This arm is administered a glyburide bolus followed by continuous infusion of glyburide for 72 hours
Intervention: Glyburide for Injection
Outcomes
Primary Outcomes
Percentage of Participants With All Four MRI Assessments Per Protocol
Time Frame: Up to Day 3
Number of MRI Assessments Per Participant
Time Frame: Up to Day 3
Percentage of Participants Requiring One or More Hypoglycemia Treatments
Time Frame: Up to Day 4
Rate of Enrollment
Time Frame: Day 1
The number of months to enroll 10 participants.
Percentage of Enrolled Participants to Screened Participants
Time Frame: Day 1
Percentage of Participants Completing 90-Day Follow-Up
Time Frame: Day 90
Percentage of Dose Reductions/ Dose Suspensions
Time Frame: Up to Day 3
Percentage of Participants With Pre-specified Adverse Events Associated With Glyburide According to Protocol
Time Frame: Up to Day 4
Secondary Outcomes
- Frequency of Hemorrhagic Events(Day 1, Day 2, and Day 3)
- National Institute of Health Stroke Scale (NIHSS) Score(Baseline, Day 1, Day 2, Day 3, and Day 7)
- Number of Participants With Adverse Events and Serious Adverse Events(Up to Day 90)
- Infarcted Hemisphere Volume(Baseline, Day 1, Day 2, and Day 3)
- Absolute Diffusion Weighted Imaging (DWI) Lesion Volume(Baseline, Day 1, Day 2, and Day 3)
- Change From Baseline in DWI Lesion Volume(Baseline, Day 1, Day 2, and Day 3 (Day 3 reported))
- Midline Shift(Baseline, Day 1, Day 2, and Day 3)
- Ipsilateral Ventricle Volume(Baseline, Day 1, Day 2, and Day 3)
- Glasgow Coma Scale (GCS) Score(Baseline, Day 1, Day 2, Day 3, and Day 7)
- Full Outline of UnResponsiveness (FOUR) Score(Baseline, Day 1, Day 2, Day 3, and Day 7)
- Number of Participants Requiring Decompressive Craniectomy (DC)(Up to Day 90)
- Number of Participants With a Modified Rankin Scale (mRS) Score ≤ 4(Day 30, Day 90)