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

NCT01454154 | Completed Phase 2 DMC

• 2 other identifiers: RPI 202INTRuST-GLY
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Change from Baseline in Brain Volume

  Baseline, Day 3, Day 90, and Day 180

• Number of Participants with Abnormalities Associated with Brain Swelling

  Baseline, Day 3, Day 90, and Day 180

• Change from Baseline in Glasgow Coma Scale (GCS)

  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)

  Day 30, Day 60, Day 90, and Day 180

Study Arms (2)

Glyburide

EXPERIMENTAL

Glyburide delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Drug: Glyburide

Placebo

PLACEBO COMPARATOR

Matching placebo delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Drug: Placebo

Interventions

Glyburide DRUG

Administered as specified in the Treatment Arm.

Also known as: RP-1127, glibenclamide, glybenclamide

Glyburide

Placebo DRUG

Administered as specified in the Treatment Arm.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented closed head TBI
• Clearly defined time of injury no more than 10 hours before administration of study drug/placebo
• 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.
• Age 18-75 years
• Patients in whom a dedicated peripheral IV line can be placed for study drug administration
• Written consent obtained from legally authorized representative (LAR)

You may not qualify if:

• No documented TBI or time of impact not certain
• Penetrating brain injury
• Spinal column instability and/or spinal cord injury with neurodeficit
• Concomitant severe non survivable injury
• Pregnant, or a positive pregnancy test
• Women who intend to breastfeed during Study Days 1-4.
• Blood glucose \<50mg/dL
• Severe renal disorder from the patient's history (e.g. dialysis) or serum creatinine of \> 2.5 mg/dL
• Severe liver disease or total bilirubin \>1.5 times upper limit of normal
• INR\>1.4
• Systolic BP\<90 mm Hg not responsive to fluid resuscitation
• Blood alcohol \> 250mg/dL
• Inability to have MRI (pacemaker, non-MR compatible pressure monitor, etc.)
• Hospitalization for brain injury, psychiatric or neurological disease within previous 3 years
• Emergent or urgent surgical operation anticipated (in OR, bedside procedures excluded) that would prevent dosing with study drug within 8 hours of injury.

Sponsors & Collaborators

• Remedy Pharmaceuticals, Inc.: lead
• U.S. Army Medical Research and Development Command: collaborator
• INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium: collaborator

Study Sites (4)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of Maryland Medical Center, Shock Trauma Center

Baltimore, Maryland, 21201, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Medical Director

  Remedy Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: October 18, 2011
• Study Start: December 17, 2011
• Primary Completion: February 20, 2015
• Study Completion: February 20, 2015
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (4)