Glyburide Advantage in Malignant Edema and Stroke - Remedy Pharmaceuticals "GAMES-RP"

Active, not recruiting

Phase 2 Results N/A

Update History

3 Jun '15
The Summary of Purpose was updated.
New
This is a randomized, multi-center, prospective, double blind study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC).
Old
This is a randomized, multi-center, prospective, double blind, two-stage, adaptive study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC).
The description was updated.
New
The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 300 cm3, age 18-80 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke. Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.
Old
The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 300 cm3, age 18-80 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke. Stage 1 of the study will enroll and treat up to a maximum of 50 subjects (25 per arm) who meet all inclusion/exclusion. Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.
A location was updated in Tucson.
New
The overall status was removed for University of Arizona Medical Center.
A location was updated in Stanford.
New
The overall status was removed for Stanford University Medical Center.
A location was updated in New Haven.
New
The overall status was removed for Yale University School of Medicine.
A location was updated in Jacksonville.
New
The overall status was removed for University of Florida, Jacksonville.
A location was updated in Chicago.
New
The overall status was removed for Northwestern Memorial Hospital.
A location was updated in Louisville.
New
The overall status was removed for University of Louisville Hospital.
A location was updated in Scarborough.
New
The overall status was removed for Maine Medical Center.
A location was updated in Baltimore.
New
The overall status was removed for University of Maryland School of Medicine.
A location was updated in Boston.
New
The overall status was removed for Massachusetts General Hospital.
A location was updated in Worcester.
New
The overall status was removed for UMass Memorial Medical Center.
A location was updated in Cleveland.
New
The overall status was removed for Cleveland Clinic.
A location was updated in Columbus.
New
The overall status was removed for Ohio State University Wexner Medical Center.
A location was updated in Portland.
New
The overall status was removed for Oregon Health & Science University Hospital.
A location was updated in Abington.
New
The overall status was removed for Abington Memorial Hospital.
A location was updated in Pittsburgh.
New
The overall status was removed for UPMC Presbyterian Hospital.
A location was updated in Charleston.
New
The overall status was removed for Medical University of South Carolina.
A location was updated in Salt Lake City.
New
The overall status was removed for University of Utah Healthcare.
5 Jun '14
A location was updated in Jacksonville.
New
The overall status was removed for University of Florida, Jacksonville.
A location was updated in Columbus.
New
The overall status was removed for Ohio State University Wexner Medical Center.
16 May '14
A location was updated in Charleston.
New
The overall status was removed for Medical University of South Carolina.
18 Dec '13
The Summary of Purpose was updated.
New
This is a randomized, multi-center, prospective, double blind, two-stage, adaptive study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC).
Old
This is a randomized, multi-center, prospective, double blind, two-stage, adaptive study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without the need for decompressive craniectomy (DC).
The description was updated.
New
The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 300 cm3, age 18-80 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke. Stage 1 of the study will enroll and treat up to a maximum of 50 subjects (25 per arm) who meet all inclusion/exclusion. Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.
Old
The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 210 cm3, age 18-75 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke. The study will enroll up to a maximum of 240 subjects (120 subjects per treatment arm). Once 50 subjects (25 per arm) are enrolled and followed through Day 90, an interim analysis will be conducted. If the trial is to continue, the sample size will be re-estimated (based on the nuisance parameter). Total enrollment will therefore be a minimum of 50 subjects (25 subjects per treatment arm) and a maximum of 240 subjects (120 subjects per treatment arm). Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.
The eligibility criteria were updated.
New
Inclusion Criteria: - A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable). - Prior to stroke, no disability, or no significant disability despite symptoms (able to carry out all usual duties and activities). - A baseline DWI lesion between 82 and 300 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 at the time of rtPA administration (if rtPA is administered in the 3-4.5 hr time window, the NIHSS must be ≤ 25 at the time of rtPA administration). - The time to the start of infusion of Study Drug must be ≤ 10 hours after time of symptom onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]. - Age ≥18 years and ≤80 years. - Provision of written informed consent by a legally authorized representative according to institutional guidelines and national regulations. Exclusion Criteria: - Commitment to decompressive craniectomy (DC) prior to enrollment, or following enrollment and prior to start of Study Drug. - Treatment with intra-arterial (IA) rtPA or by mechanical means for clot disruption. - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators. - Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere deemed by the investigator to be sufficiently serious so as to affect functional outcome. - Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes attributable to edema or herniation according to the investigator's judgment. - Hemorrhage (other than small petechial hemorrhages) on CT/MRI, or CT/MRI evidence of anteroseptal/pineal shift greater ≥2 mm prior to enrollment that is due to cerebral edema. - 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 >3 times normal, or bilirubin >2 times normal. - Blood glucose <55 mg/dL at enrollment or immediately prior to administration of Study Drug, or a clinically significant history of hypoglycemia. - Acute ST elevation myocardial infarction, and/or acute decompensated HF, and/or QTc>520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an ACS, MI, or coronary intervention (PCI or coronary artery surgery) within the past 3 months. - Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide /glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); netaglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); glibornuride (Glutril). - Known allergy to sulfa or specific allergy to sulfonylurea drugs. - Known G6PD enzyme deficiency. - Pregnant women. Women must be either post-menopausal (as confirmed by the LAR), permanently sterilized or, if ≤ 50 years old must have a negative test for pregnancy obtained before enrollment. - Breast-feeding women who do not agree (or their LAR does not agree) to stop breast- feeding during Study Drug infusion and for 7 days following the end of Study Drug infusion. - 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 compliant with follow up. - Patients currently receiving an investigational drug. - Patients in whom a peripheral IV line cannot be placed. - Mentally incompetent (prior to qualifying stroke) patients and wards of the state. - Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented).
Old
Inclusion Criteria: - A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory. - Pre-morbid mRS 0 - 1 [prior to stroke, no disability, or no significant disability despite symptoms (able to carry out all usual duties and activities)]. - A baseline DWI lesion between 82 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 at the time of rtPA administration (if rtPA is administered in the 3-4.5 hr time window, the NIHSS must be ≤ 25 at the time of rtPA administration). - The time to the start of infusion of Study Drug must be ≤ 10 hours after time of symptom onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]. - Age ≥18 years and ≤75 years. - Provision of written informed consent by a legally authorized representative according to institutional guidelines and national regulations. Exclusion Criteria: - Commitment to decompressive craniectomy (DC) prior to enrollment, or following enrollment and prior to start of Study Drug. - Treatment with intra-arterial (IA) rtPA or by mechanical means for clot disruption or with hypothermia. - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators. - 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. - Hemorrhage (other than small petechial hemorrhages) on CT/MRI, or CT/MRI evidence of anteroseptal/pineal shift greater ≥2 mm prior to enrollment that is due to cerebral edema. - 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 Study Drug, or a clinically significant history of hypoglycemia. - Acute ST elevation myocardial infarction, and/or acute decompensated HF, and/or QTc>520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an ACS, MI, or coronary intervention (PCI or coronary artery surgery) within the past 3 months. - Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide /glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); glibornuride (Glutril). - Known allergy to sulfa or specific allergy to sulfonylurea drugs. - Known G6PD enzyme deficiency. - Pregnant women. Women must be either post-menopausal (as confirmed by the LAR), permanently sterilized or, if ≤ 50 years old must have a negative test for pregnancy obtained before enrollment. - Breast-feeding women who do not agree (or their LAR does not agree) to stop breast- feeding during Study Drug infusion and for 7 days following the end of Study Drug infusion. - 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 compliant with follow up. - Patients currently receiving an investigational drug. - Patients in whom a peripheral IV line cannot be placed. - Mentally incompetent (prior to qualifying stroke) patients and wards of the state. - Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented).
20 Nov '13
A location was updated in Stanford.
New
The overall status was removed for Stanford University Medical Center.
A location was updated in Chicago.
New
The overall status was removed for Northwestern Memorial Hospital.
A location was updated in Louisville.
New
The overall status was removed for University of Louisville Hospital.
A location was updated in Scarborough.
New
The overall status was removed for Maine Medical Center.
A location was updated in Baltimore.
New
The overall status was removed for University of Maryland School of Medicine.
A location was updated in Worcester.
New
The overall status was removed for UMass Memorial Medical Center.
A location was updated in Portland.
New
The overall status was removed for Oregon Health & Science University Hospital.
A location was updated in Charleston.
New
The overall status was removed for Medical University of South Carolina.
14 May '13
A location was updated in New Haven.
New
The overall status was removed for Yale University School of Medicine.
7 May '13
A location was updated in Boston.
New
The overall status was removed for Massachusetts General Hospital.