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

Phase 2

Completed

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Placebo; Drug: Glyburide

• Registration Number: NCT01454154
• Lead Sponsor: Remedy Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2011-10-11
• Study First Submitted QC: 2011-10-17
• Study First Posted: 2011-10-18
• Study Start: 2011-12-17
• Primary Completion: 2015-02-20
• Study Completion: 2015-02-20
• Disposition First Submitted: 2023-08-16
• Disposition First Posted: 2023-08-21
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.
Glyburide	Glyburide	Glyburide delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Hemorrhage	Baseline, Day 3, Day 90, and Day 180	To be assessed using MRI.
Change from Baseline in Edema	Baseline, Day 3, Day 90, and Day 180	To be assessed using Magnetic Resonance Imaging (MRI).
Number of Participants with Adverse Events and Serious Adverse Events	Up to 180 Days	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

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Glasgow Coma Scale (GCS)	Baseline up to Day 7	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)
Number of Participants with Abnormalities Associated with Brain Swelling	Baseline, Day 3, Day 90, and Day 180	To be assessed using MRI and computed tomography (CT).
Number of All-Cause and Neurological Mortalities	Up to Day 180
Change from Baseline in Intracranial Pressure (ICP)	Baseline up to Day 7
Change from Baseline in Brain Volume	Baseline, Day 3, Day 90, and Day 180	To be assessed using MRI.
Change from Day 30 in Extended Glasgow Outcome Scale (GOS-E)	Day 30, Day 60, Day 90, and Day 180	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
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

Trial Locations

Locations (4)

UPMC Presbyterian Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Maryland Medical Center, Shock Trauma Center; 🇺🇸 Baltimore, Maryland, United States

University of California, San Diego; 🇺🇸 San Diego, California, United States

VCU Medical Center; 🇺🇸 Richmond, Virginia, United States