Glyburide Advantage in Malignant Edema and Stroke - Remedy Pharmaceuticals

Ischemic Stroke Clinical Trial

— GAMES-RP  

Official title:

A Randomized, Multi-Center, Prospective, Double Blind, Phase II Trial of RP- 1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Develop Malignant Edema

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01794182
• Other study ID #: 252LH203
• Secondary ID: RPI 203
• Status: Completed
• Phase: Phase 2
• Start date: June 13, 2013
• Est. completion date: April 4, 2016

Study information

• Verified date: April 2024
• Source: Remedy Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, multi-center, prospective, double blind study. The primary objective is to assess the efficacy and safety of glyburide (RP-1127) compared to placebo in participants with a severe anterior circulation ischemic stroke who are likely to develop malignant edema.This objective will be addressed by comparing the proportion of glyburide treated particpants and placebo treated participants with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC). The secondary objective is to assess the efficacy of RP-1127 compared to placebo in participants with a severe anterior circulation ischemic stroke who were likely to develop malignant edema.

Description:

The study population consists of participants 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 participants that do not receive intravenous (IV) recombinant tissue plasminogen activator (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). Participants will be randomized equally between glyburide and placebo.

This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: April 4, 2016
• Est. primary completion date: April 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key 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)].

• Provision of written informed consent by a legally authorized representative according to institutional guidelines and national regulations.

Key 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).

NOTE: Other protocol defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Anthrax
• Edema
• Gas Gangrene
• Ischemic Stroke
• Malignant Edema
• Stroke

Intervention

Drug:
• Glyburide for Injection
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	University of Florida, Jacksonville	Jacksonville	Florida
United States	University of Louisville Hospital	Louisville	Kentucky
United States	Yale University School of Medicine	New Haven	Connecticut
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Hospital	Portland	Oregon
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	Maine Medical Center	Scarborough	Maine
United States	Stanford University Medical Center	Stanford	California
United States	University of Arizona Medical Center	Tucson	Arizona
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Remedy Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with a Modified Rankin Scale (mRS) score of = 4 Without Decompressive Craniectomy (DC)	The mRS scale runs from 0-6, the scoring is as follows: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead	Day 90
Primary	Number of Participants with Adverse Events and Serious Adverse Events	An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. A serious adverse event is any AE that is fatal, life-threatening, requires or prolongs hospital stay, results in persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event	Up to 1 Year
Secondary	Percentage of Participants Undergoing DC or Dead		Baseline and Day 14
Secondary	Change from Baseline in Ipsilateral Hemispheric Swelling	To be assessed using Magnetic Resonance Imaging (MRI).	Baseline up to 72-96 Hours
Secondary	Change from Baseline in Lesional Swelling	To be assessed using MRI.	Baseline up to 72-96 Hours