Glyburide Advantage in Malignant Edema and Stroke Pilot

NCT01268683 | Completed Phase 1 Results DMC

• 1 other identifier: RPI 201
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is to assess the feasibility of enrolling, evaluating, and treating with glyburide for injection severe anterior circulation ischemic stroke participants, whether or not treated with standard of care intravenous (IV) recombinant tissue plasminogen activator (rtPA). Participants must be between 18-80 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 -210 centimeters cubed (cm3), and time from symptom onset to start of study infusion must be ≤10 hour(hr). The secondary objectives are to assess the initial safety and tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of glyburide in severe stroke participants, as well as to compare the clinical and magnetic resonance imaging (MRI) outcome data to benchmark data derived from published literature.

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (8)

• Rate of Enrollment

  The number of months to enroll 10 participants.

  Day 1

• Percentage of Enrolled Participants to Screened Participants

  Day 1

• Percentage of Participants Completing 90-Day Follow-Up

  Day 90

• Percentage of Dose Reductions/ Dose Suspensions

  Up to Day 3

• Percentage of Participants With All Four MRI Assessments Per Protocol

  Up to Day 3

• Number of MRI Assessments Per Participant

  Up to Day 3

• Percentage of Participants Requiring One or More Hypoglycemia Treatments

  Up to Day 4

• Percentage of Participants With Pre-specified Adverse Events Associated With Glyburide According to Protocol

  Up to Day 4

Secondary Outcomes (12)

• Number of Participants With Adverse Events and Serious Adverse Events

  Up to Day 90

• Infarcted Hemisphere Volume

  Baseline, Day 1, Day 2, and Day 3

• Absolute Diffusion Weighted Imaging (DWI) Lesion Volume

  Baseline, Day 1, Day 2, and Day 3

• Change From Baseline in DWI Lesion Volume

  Baseline, Day 1, Day 2, and Day 3 (Day 3 reported)

• Midline Shift

  Baseline, Day 1, Day 2, and Day 3

Study Arms (1)

Glyburide for Injection

EXPERIMENTAL

This arm is administered a glyburide bolus followed by continuous infusion of glyburide for 72 hours

Drug: Glyburide for Injection

Interventions

Glyburide for Injection DRUG

Administered as specified in the treatment arm.

Also known as: RP-1127, glibenclamide, glybenclamide

Glyburide for Injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Remedy Pharmaceuticals, Inc.: lead
• University of Maryland: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (4)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN. Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care. 2014 Apr;20(2):193-201. doi: 10.1007/s12028-013-9917-z.

  PMID: 24072459 BACKGROUND

• Sheth KN, Kimberly WT, Elm JJ, Kent TA, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, del Zoppo G, Simard JM, Stern BJ, Mandava P. Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care. 2014 Aug;21(1):43-51. doi: 10.1007/s12028-014-9970-2.

  PMID: 24671831 BACKGROUND

• Sheth KN, Kimberly WT, Elm JJ, Kent TA, Mandava P, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, Simard JM, Stern BJ. Pilot study of intravenous glyburide in patients with a large ischemic stroke. Stroke. 2014 Jan;45(1):281-3. doi: 10.1161/STROKEAHA.113.003352. Epub 2013 Nov 5.

  PMID: 24193798 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Glyburide; Injections

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

The trial was a single arm; there is thus no placebo to compare RP-1127 to.

Results Point of Contact

• Title: Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Remedy Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2010
• First Posted: December 31, 2010
• Study Start: May 26, 2011
• Primary Completion: June 7, 2012
• Study Completion: June 7, 2012
• Last Updated: November 22, 2024
• Results First Posted: June 6, 2014

Record last verified: 2024-11

Locations

US (4)