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

Condition(s) targeted: Traumatic Brain Injury

Intervention: Glyburide (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Remedy Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Howard Eisenberg, MD, Principal Investigator, Affiliation: University of Maryland

Overall contact:
Howard Eisenberg, MD, Phone: (410) 328-3514, Email: heisenberg@smail.umaryland.edu

This is a randomized, double-blind, placebo-controlled, multi-institutional study of IV RP-1127 (Glyburide for Injection) begun within 10 hours of complicated mild, moderate or severe traumatic brain injury (TBI).

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Change in Edema from Baseline

Change in Hemorrhage from Baseline

Safety i.e. the incidence of mortality, adverse events, and serious adverse events

Detailed description: The primary efficacy objective of this study is to assess whether patients with severe, moderate, or complicated mild TBI administered RP-1127 will show a decrease in MRI-defined edema and/or hemorrhage, compared to patients administered placebo.

The primary safety objective is to assess the safety and tolerability of RP-1127 compared to placebo in patients with severe, moderate, or complicated mild TBI.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Howard Eisenberg, MD, Phone: (410) 328-3514, Email: heisenberg@smail.umaryland.edu

University of California, San Diego, San Diego, California 92103, United States; Recruiting
Vishal Bansal, MD, Phone: 619-543-7096, Email: v3bansal@ucsd.edu

University of Maryland Medical Center, Shock Trauma Center, Baltimore, Maryland 21201, United States; Recruiting
Howard Eisenberg, MD, Phone: 410-328-3514, Email: heisenberg@smail.umaryland.edu

Starting date: November 2011
Last updated: January 21, 2013