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

This study has been completed.
Sponsor:
Collaborators:
University of Maryland
Massachusetts General Hospital
Information provided by (Responsible Party):
Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01268683
First received: December 29, 2010
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

The study objective is to assess the feasibility of enrolling, evaluating, and treating with RP-1127 (Glyburide for Injection) severe anterior circulation ischemic stroke patients, whether or not treated with standard of care IV rtPA. Patients must be between 18-60 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 - 210 cm3, and time from symptom onset to start of study infusion must be ≤10 hr.


Condition Intervention Phase
Ischemic Stroke
Drug: RP-1127 (Glyburide for injection)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Feasibility of recruiting target population [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    AE's of special interest (cardiac events, difficulty controlling blood sugar, liver problems, and blood disorders, including anemia) will be followed for 30 days and all SAE's will be followed for 90 days.

  • Pharmacokinetics/pharmacodynamics [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
  • Clinical and MRI outcome data [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: May 2011
Study Completion Date: February 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RP-1127 (Glyburide for Injection) Drug: RP-1127 (Glyburide for injection)
Bolus plus 72 hour IV infusion
Other Name: glibenclamide

Detailed Description:

This is a multi-center, prospective, open label, Phase IIa trial of RP-1127 (Glyburide for Injection) in 10 patients with a severe anterior circulation ischemic stroke who are likely to experience clinically significant brain swelling.

Subjects will receive RP-1127 (Glyburide for Injection), delivered as an IV bolus followed by an IV infusion for 72 hours.

Subjects 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 NIHSS, GCS and FOUR Score (baseline, 24±12 hour, 48±12 hour, 72±12 hour and 7±1 days) and 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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 (rea-son to be documented).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01268683

Locations
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Remedy Pharmaceuticals, Inc.
University of Maryland
Massachusetts General Hospital
Investigators
Principal Investigator: Kevin Sheth, MD University of Maryland
  More Information

No publications provided by Remedy Pharmaceuticals, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01268683     History of Changes
Other Study ID Numbers: RPI 201
Study First Received: December 29, 2010
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Remedy Pharmaceuticals, Inc.:
Ischemic stroke

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014