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

Primary Purpose

Traumatic Brain Injury

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Glyburide

Placebo

About this trial

This is an interventional treatment trial for Traumatic Brain Injury

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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.
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.)
Use of sulfonylurea drugs within the prior 30 days
Treatment with another investigational drug within the prior 30 days
Allergy to sulfonylurea drugs
Known diagnosis of G6PD enzyme deficiency
PaO2 < 60 mm Hg on admission (for patients in whom blood gases are drawn per standard of care)
Non-English speaking legally authorized representative and subjects (University of Maryland only)
Prisoners or others who may be unable to make a truly voluntary and uncoerced decision whether or not to participate in the study
Any other clinical condition which in the opinion of the investigator makes the patient unsuitable for inclusion into the study

Sites / Locations

University of California, San Diego
University of Maryland Medical Center, Shock Trauma Center
UPMC Presbyterian Hospital
VCU Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Glyburide

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change from Baseline in Edema

To be assessed using Magnetic Resonance Imaging (MRI).

Change from Baseline in Hemorrhage

To be assessed using MRI.

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

Secondary Outcome Measures

Change from Baseline in Brain Volume

To be assessed using MRI.

Number of Participants with Abnormalities Associated with Brain Swelling

To be assessed using MRI and computed tomography (CT).

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)

Change from Baseline in Intracranial Pressure (ICP)

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

Number of Participants Requiring Decompression Craniectomy

Number of Participants Experiencing Neuroworsening

PK Parameter: Steady State Concentration of Glyburide

Number of All-Cause and Neurological Mortalities

Full Information

NCT ID

NCT01454154

First Posted

October 11, 2011

Last Updated

August 16, 2023

Sponsor

Biogen

Collaborators

U.S. Army Medical Research and Development Command, INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium

1. Study Identification

Unique Protocol Identification Number

NCT01454154

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

December 17, 2011 (Actual)

Primary Completion Date

February 20, 2015 (Actual)

Study Completion Date

February 20, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biogen

Collaborators

U.S. Army Medical Research and Development Command, INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Glyburide

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Glyburide

Other Intervention Name(s)

RP-1127, glibenclamide, glybenclamide

Intervention Description

Administered as specified in the Treatment Arm.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered as specified in the Treatment Arm.

Primary Outcome Measure Information:

Title

Change from Baseline in Edema

Description

To be assessed using Magnetic Resonance Imaging (MRI).

Time Frame

Baseline, Day 3, Day 90, and Day 180

Title

Change from Baseline in Hemorrhage

Description

To be assessed using MRI.

Time Frame

Baseline, Day 3, Day 90, and Day 180

Title

Number of Participants with Adverse Events and Serious Adverse Events

Description

Time Frame

Up to 180 Days

Secondary Outcome Measure Information:

Title

Change from Baseline in Brain Volume

Description

To be assessed using MRI.

Time Frame

Baseline, Day 3, Day 90, and Day 180

Title

Number of Participants with Abnormalities Associated with Brain Swelling

Description

To be assessed using MRI and computed tomography (CT).

Time Frame

Baseline, Day 3, Day 90, and Day 180

Title

Change from Baseline in Glasgow Coma Scale (GCS)

Description

Time Frame

Baseline up to Day 7

Title

Change from Baseline in Intracranial Pressure (ICP)

Time Frame

Baseline up to Day 7

Title

Change from Day 30 in Extended Glasgow Outcome Scale (GOS-E)

Description

Time Frame

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

Title

Number of Participants Requiring Decompression Craniectomy

Time Frame

Baseline up to Day 7

Title

Number of Participants Experiencing Neuroworsening

Time Frame

Baseline up to Day 7

Title

PK Parameter: Steady State Concentration of Glyburide

Time Frame

Baseline and 36 hours

Title

Number of All-Cause and Neurological Mortalities

Time Frame

Up to Day 180

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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. 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.) Use of sulfonylurea drugs within the prior 30 days Treatment with another investigational drug within the prior 30 days Allergy to sulfonylurea drugs Known diagnosis of G6PD enzyme deficiency PaO2 < 60 mm Hg on admission (for patients in whom blood gases are drawn per standard of care) Non-English speaking legally authorized representative and subjects (University of Maryland only) Prisoners or others who may be unable to make a truly voluntary and uncoerced decision whether or not to participate in the study Any other clinical condition which in the opinion of the investigator makes the patient unsuitable for inclusion into the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Biogen

Official's Role

Study Director

Facility Information:

Facility Name

University of California, San Diego

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

University of Maryland Medical Center, Shock Trauma Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

UPMC Presbyterian Hospital

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

VCU Medical Center

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

12. IPD Sharing Statement

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

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