Glyburide (RP-1127) for Traumatic Brain Injury (TBI)

A Randomized Clinical Trial of Glyburide (RP-1127) for TBI

The primary objectives of this study are to assess whether participants with traumatic brain injury (TBI) administered glyburide begun within 10 hours of injury will show a decrease in magnetic resonance imaging (MRI)-defined edema and/or hemorrhage, compared to placebo and to assess the safety and tolerability of glyburide compared to placebo in participants with TBI. The secondary objectives include analyzing brain cell loss, computerized tomography (CT) scan /MRI abnormalities, reduction of mortality and or improvement of function or physiology, incidence of decompression craniectomy, incidence of neuroworsening, and to assess the steady state concentrations of glyburide in TBI participants.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Glyburide; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • University of California, San Diego
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center, Shock Trauma Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Documented closed head TBI
2. Clearly defined time of injury no more than 10 hours before administration of study drug/placebo
3. GCS 4-14. The GCS will be obtained free of the effects of sedating and/or paralytic drug. Complicated mild must have GCS 13-14 and one or more of the following: Intraparenchymal clots or contusions in aggregate > 10cc; Midline shift > 5mm; IVH, SDH, EDH seen on more than one CT scan slice.
4. Age 18-75 years
5. Patients in whom a dedicated peripheral IV line can be placed for study drug administration
6. Written consent obtained from legally authorized representative (LAR)

Exclusion Criteria:

1. No documented TBI or time of impact not certain
2. Penetrating brain injury
3. Spinal column instability and/or spinal cord injury with neurodeficit
4. Concomitant severe non survivable injury
5. Pregnant, or a positive pregnancy test
6. Women who intend to breastfeed during Study Days 1-4.
7. Blood glucose <50mg/dL
8. Severe renal disorder from the patient's history (e.g. dialysis) or serum creatinine of > 2.5 mg/dL
9. Severe liver disease or total bilirubin >1.5 times upper limit of normal
10. INR>1.4
11. Systolic BP<90 mm Hg not responsive to fluid resuscitation
12. Blood alcohol > 250mg/dL
13. Inability to have MRI (pacemaker, non-MR compatible pressure monitor, etc.)
14. Hospitalization for brain injury, psychiatric or neurological disease within previous 3 years
15. Emergent or urgent surgical operation anticipated (in OR, bedside procedures excluded) that would prevent dosing with study drug within 8 hours of injury.
16. Known use of Coumadin (warfarin), Plavix (clopidogrel), Effient (prasugrel) or Pletal (cilostazol), heparin, low molecular weight heparin, heparinoids, or abciximab or similar antiplatelet agents in the previous 72 hours (Note that patients later found to have taken these medications will not be automatically excluded from the study.)
17. Use of sulfonylurea drugs within the prior 30 days
18. Treatment with another investigational drug within the prior 30 days
19. Allergy to sulfonylurea drugs
20. Known diagnosis of G6PD enzyme deficiency
21. PaO2 < 60 mm Hg on admission (for patients in whom blood gases are drawn per standard of care)
22. Non-English speaking legally authorized representative and subjects (University of Maryland only)
23. Prisoners or others who may be unable to make a truly voluntary and uncoerced decision whether or not to participate in the study
24. Any other clinical condition which in the opinion of the investigator makes the patient unsuitable for inclusion into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glyburide; Glyburide delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.	Drug: Glyburide; Administered as specified in the Treatment Arm.; Other Names: RP-1127; glibenclamide; glybenclamide
Placebo Comparator: Placebo; Matching placebo delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.	Drug: Placebo; Administered as specified in the Treatment Arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Edema	To be assessed using Magnetic Resonance Imaging (MRI).	Baseline, Day 3, Day 90, and Day 180
Change from Baseline in Hemorrhage	To be assessed using MRI.	Baseline, Day 3, Day 90, and Day 180
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 180 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Brain Volume	To be assessed using MRI.	Baseline, Day 3, Day 90, and Day 180
Number of Participants with Abnormalities Associated with Brain Swelling	To be assessed using MRI and computed tomography (CT).	Baseline, Day 3, Day 90, and Day 180
Change from Baseline in Glasgow Coma Scale (GCS)	The GCS is scored between 3 and 15 (3 = the worst, and 15 = best). It is composed of three parameters : Best Eye Response (scored on a scale of 1-4), Best Verbal Response (scored on a scale of 1-5), Best Motor Response (scored on a scale of 1-6)	Baseline up to Day 7
Change from Baseline in Intracranial Pressure (ICP)		Baseline up to Day 7
Change from Day 30 in Extended Glasgow Outcome Scale (GOS-E)	The GOS-E assesses status in patients with traumatic brain injury on an 8-point scale. The minimum score is 1 and the maximum score is 8. The rating scale is as follows: 1- Dead, 2- Vegetative State, 3- Low Severe Disability, 4- Upper Severe Disability, 5- Low Moderate Disability, 6- Upper Moderate Disability, 7- Low Good Recovery, and 8- Upper Good Recovery	Day 30, Day 60, Day 90, and Day 180
Number of Participants Requiring Decompression Craniectomy		Baseline up to Day 7
Number of Participants Experiencing Neuroworsening		Baseline up to Day 7
PK Parameter: Steady State Concentration of Glyburide		Baseline and 36 hours
Number of All-Cause and Neurological Mortalities		Up to Day 180

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: U.S. Army Medical Research and Development Command; INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2011
• Primary Completion (Actual): February 20, 2015
• Study Completion (Actual): February 20, 2015

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (Estimated): October 18, 2011

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: RPI 202; INTRuST-GLY (Other Identifier: INTRuST Clinical Consortium Coordinating Center)