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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01454154
• Other study ID #: RPI 202
• Secondary ID: INTRuST-GLY
• Status: Completed
• Phase: Phase 2
• Start date: December 17, 2011
• Est. completion date: February 20, 2015

Study information

• Verified date: April 2024
• Source: Remedy Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 20, 2015
• Est. primary completion date: February 20, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury

Intervention

Drug:
• Glyburide
Administered as specified in the Treatment Arm.
• Placebo
Administered as specified in the Treatment Arm.

Locations

Country	Name	City	State
United States	University of Maryland Medical Center, Shock Trauma Center	Baltimore	Maryland
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	VCU Medical Center	Richmond	Virginia
United States	University of California, San Diego	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
Remedy Pharmaceuticals, Inc.	INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium, U.S. Army Medical Research and Development Command

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Edema	To be assessed using Magnetic Resonance Imaging (MRI).	Baseline, Day 3, Day 90, and Day 180
Primary	Change from Baseline in Hemorrhage	To be assessed using MRI.	Baseline, Day 3, Day 90, and Day 180
Primary	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	Change from Baseline in Brain Volume	To be assessed using MRI.	Baseline, Day 3, Day 90, and Day 180
Secondary	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
Secondary	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
Secondary	Change from Baseline in Intracranial Pressure (ICP)		Baseline up to Day 7
Secondary	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
Secondary	Number of Participants Requiring Decompression Craniectomy		Baseline up to Day 7
Secondary	Number of Participants Experiencing Neuroworsening		Baseline up to Day 7
Secondary	PK Parameter: Steady State Concentration of Glyburide		Baseline and 36 hours
Secondary	Number of All-Cause and Neurological Mortalities		Up to Day 180