Glyburide Advantage in Malignant Edema and Stroke Pilot (GAMES-PILOT)

Key Inclusion Criteria:

• A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory.
• Pre-morbid mRS 0 - 1.
• 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.

Key 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 ≥ 2.
• 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 m2.
• Severe liver disease or ALT, AST, or bilirubin >2 times normal.
• Blood glucose <55 mg/dL at enrollment or immediately prior to administration of RP-1127, or a clinically significant history of hypoglycemia.
• Diagnosis of decompensated heart failure (e.g. clinical diagnosis of pulmonary edema, chest x-ray consistent with heart failure, tachypnea > 20, etc.)
• Sulfonylurea treatment within 30 days.
• Known allergy to sulfa or specific allergy to sulfonylurea drugs.
• Known G6PD enzyme deficiency.
• Pregnancy or breast-feeding. Women must be either post-menopausal (judged by the investigator), permanently sterilized or, if of childbearing age, must have a negative test for pregnancy obtained before enrollment.
• Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be com-pliant with follow up.
• Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply