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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Remedy Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01794182
First received: February 14, 2013
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Ischemic Stroke
Malignant Edema
Drug: RP-1127 (Glyburide for Injection)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Multi-center, Prospective, Double Blind, Two-stage, Adaptive 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

Resource links provided by NLM:


Further study details as provided by Remedy Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • The proportion of patients with a modified Rankin Scale (mRS) at Day 90 ≤ 4 without decompressive craniectomy [ Time Frame: 90 Days ] [ Designated as safety issue: No ]
  • Safety of RP-1127 in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]
    Addressed by comparing the frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)in the RP-1127 and placebo groups, with a specific focus on all cause mortality, cardiac mortality, and cardiac-related and blood glucose-related AEs/SAEs.


Secondary Outcome Measures:
  • Proportion of subjects that develop malignant edema [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Proportion of subjects undergoing DC, and DC-associated AEs and SAEs [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects that experience early neurological deterioration [ Time Frame: 72 Hours ] [ Designated as safety issue: No ]
  • Proportion of subjects that develop parenchymal hematomas [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
  • Ipsilateral hemispheric swelling measured by MRI [ Time Frame: 96 Hours ] [ Designated as safety issue: No ]
  • Proportion of subjects with 90 day mRS 0-3 and 0-4 [ Time Frame: 90 Day ] [ Designated as safety issue: No ]
  • Activities of Daily Living (as measured by the Barthel Index) at 90 days [ Time Frame: 90 Days ] [ Designated as safety issue: No ]
  • All-cause mortality at 90 days [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 240
Study Start Date: May 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Matching Placebo
Subjects will receive matching placebo.
Experimental: RP-1127 (Glyburide for Injection)
Subjects will receive the active agent, RP-1127 (Glyburide for Injection)
Drug: RP-1127 (Glyburide for Injection)
Glyburide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl]phenethyl)-2- methoxybenzamide) is an anti-diabetic medication in a class of medications known as sulfonylureas. RP-1127 is a formulation of glyburide designed for intravenous administration.
Other Names:
  • glibenclamide
  • glybenclamide

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01794182

Contacts
Contact: Kevin N Sheth, MD 203-785-5947 kevin.sheth@yale.edu
Contact: W. Taylor Kimberly, MD, PhD 857-238-5644 wtkimberly@partners.org

Locations
United States, Arizona
University of Arizona Medical Center Not yet recruiting
Tucson, Arizona, United States, 85719
Contact: Kendra Drake       kdrake@neurology.arizona.edu   
United States, California
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Gregory W Albers, MD    650-494-3848      
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Principal Investigator: Kevin N Sheth, MD         
United States, Florida
University of Florida, Jacksonville Recruiting
Jacksonville, Florida, United States, 32209
Contact: Scott Silliman       scott.silliman@jax.ufl.edu   
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Shyam K Prabhakaran, MD    312-503-2994      
United States, Kentucky
University of Louisville Hospital Recruiting
Louisville, Kentucky, United States, 40202
Contact: Ann Jerde    502-813-6579    ann.jerde@louisville.edu   
United States, Maine
Maine Medical Center Recruiting
Scarborough, Maine, United States, 04074
Contact: Paul Muscat, MD    207-883-1414      
United States, Maryland
University of Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21201
Contact: Carolyn Cronin, 410-328-3871         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: W. Taylor Kimberly, MD, PhD    857-238-5644    wtkimberly@partners.org   
Principal Investigator: W. Taylor Kimberly, MD, PhD         
UMASS Memorial Medical Center Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Raphael A Carandang, MD    508-334-2527      
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Jennifer Turczyk    216-445-4488    turczyj@ccf.org   
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Michel T Torbey, MD    614-293-4966      
United States, Oregon
Oregon Health & Science University Hospital Recruiting
Portland, Oregon, United States, 97239
Contact: Holly E Hinson, MD    503-418-1472      
United States, Pennsylvania
Abington Memorial Hospital Recruiting
Abington, Pennsylvania, United States, 19001
Contact: Osman Kozak       OKozak@abingtonhealth.org   
UPMC Presbyterian Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Bradley Molyneaux       molyneauxbj@upmc.edu   
United States, South Carolina
Medical University of South Carolina Terminated
Charleston, South Carolina, United States, 29425
United States, Utah
University of Utah Healthcare Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Jennifer Majersik       Jennifer.Majersik@hsc.utah.edu   
Sponsors and Collaborators
Remedy Pharmaceuticals, Inc.
Investigators
Principal Investigator: Kevin N Sheth, MD Yale University
Principal Investigator: W. Taylor Kimberly, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01794182     History of Changes
Other Study ID Numbers: RPI 203
Study First Received: February 14, 2013
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gas Gangrene
Stroke
Cerebral Infarction
Ischemia
Edema
Anthrax
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Pathologic Processes
Signs and Symptoms
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacillaceae Infections
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014