Study of NNZ-2566 in Patients With Traumatic Brain Injury

NCT ID: NCT00805818

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 261 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2016-01-31

Brief Summary

The purpose of this study is to determine whether NNZ-2566 is safe and effective in the treatment of Traumatic Brain Injury (TBI).

Detailed Description

Moderate to severe traumatic brain injury frequently results in persistent problems with memory, attention span, mood and more complex brain functioning such as planning and organizing. There are currently no drugs available to reduce the brain damage or the persisting symptoms that result from TBI. The longer term goal of this study is to provide physicians with a safe and effective treatment for TBI.

Conditions

Brain Injuries

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

NNZ-2566

20 mg/kg intravenous bolus infusion over 10 minutes followed by a continuous intravenous infusion of 1 mg/kg/h (Cohort 1, n=20), 3 mg/kg/h (Cohort 2, n=20) or 6 mg/kg/h (Cohort 3, n=133) intravenous infusion for a total of 72 consecutive hours.

Group Type: EXPERIMENTAL

NNZ-2566

Intervention Type: DRUG

Solution for intravenous infusion.

20 mg/kg intravenous bolus infusion over 10 minutes followed by a continuous intravenous infusion of 1, 3, or 6 mg/kg/h for a total of 72 consecutive hours.

Sodium Chloride (0.9%) for Injection

Intravenous bolus infusion over 10 minutes followed by a continuous intravenous infusion (Cohort 1, n=10), (Cohort 2, n=10) or (Cohort 3, n=67) intravenous infusion for a total of 72 consecutive hours.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium Chloride 0.9% Injection

Interventions

NNZ-2566

Solution for intravenous infusion.

20 mg/kg intravenous bolus infusion over 10 minutes followed by a continuous intravenous infusion of 1, 3, or 6 mg/kg/h for a total of 72 consecutive hours.

Intervention Type: DRUG

Placebo

Sodium Chloride 0.9% Injection

Intervention Type: DRUG

Other Intervention Names

Glycyl-L-2-Methylprolyl-L-Glutamic Acid; Sodium Chloride 0.9% Injection

Eligibility Criteria

Inclusion Criteria

• Non-penetrating TBI.
• Male.
• Age 18-70 years.
• Admission to hospital.
• Post resuscitation GCS 4-12.
• Have at least one reactive pupil.
• Randomization within 7 hours of injury with the ability to receive investigational product within 8 hours of injury.
• Hemodynamically stable after resuscitation (systolic blood pressure (SBP) >100 mm Hg).
• Willing to undergo all neuropsychological and activities of daily living (ADL) testing (i.e. understand English, able to read, write, have sufficient motor dexterity and, be available for follow-up visits at 4-6 weeks and 12-14 weeks post injury).

Exclusion Criteria

• Penetrating brain injury.
• Spinal cord injury.
• Presence or known history of prior cerebral injury requiring hospitalization that would, in the opinion of the Investigator, interfere with or bias the assessment of efficacy.
• Non-traumatic brain injury.
• Known history of any medical or psychiatric disorder, or any severe concomitant disease, that in the opinion of the Investigator would interfere with or bias the assessment of efficacy. This includes the following: schizophrenia; bipolar disorder; major depressive disorder; post traumatic stress disorder (PTSD); generalized anxiety disorder; attention deficit hyperactivity disorder; neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's disease, vascular dementia, Diffuse Lewy Body Disease); stroke; brain tumor; multiple sclerosis (MS); seizure disorders; chronic pain disorder; alcoholism or substance abuse.
• Significant non-central nervous system (CNS) injuries sustained at the time of the TBI that in the opinion of the Investigator would interfere with or bias the assessment of efficacy.
• Weight >150 kg.
• Participation in another clinical trial within the previous 4 weeks.
• Clinical state requiring greater than 6 L colloid or crystalloid fluid resuscitation prior to randomization.
• Inability to obtain informed consent from legally acceptable representative.
• Prior enrollment in this study.

• A marked baseline prolongation of corrected QT/QTc interval >450 ms.
• History of risk factors for torsade de pointes (e.g. heart failure, hypokalemia (serum potassium at screening (<3.0 mmol/L)or family history of long QT syndrome).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Neuren Pharmaceuticals Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ross R Bullock, M.D., PhD

Role: PRINCIPAL_INVESTIGATOR

University of Miami, Lois Pope Life Center

Locations

University of South Alabama

Mobile, Alabama, United States

University of Arizona

Tucson, Arizona, United States

Arrowhead Regional Medical Center

Colton, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

University of Miami, Lois Pope Life Center

Miami, Florida, United States

The Queen's Medical Center

Honolulu, Hawaii, United States

Our Lady of the Lake Hospital

Baton Rouge, Louisiana, United States

Detroit Receiving Hospital and University Health Center

Detroit, Michigan, United States

Sinai Grace Hospital

Detroit, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

SUNY Upstate Medical University

Syracuse, New York, United States

University of Cincinnati, Mayfield Clinic

Cincinnati, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

St Luke's University Hospital

Bethlehem, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Texas Health Harris Methodist Hospital Fort Worth

Fort Worth, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Charleston Area Medical Center

Charleston, West Virginia, United States

University of Wisconsin, Froedtert Hospital

Milwaukee, Wisconsin, United States

Countries

United States

References

Lee JW. The EEG Ictal-Interictal Continuum-A Metabolic Roar But a Whimper of a Functional Outcome. Epilepsy Curr. 2019 Jul-Aug;19(4):234-236. doi: 10.1177/1535759719855968. Epub 2019 Jun 14.

Reference Type: DERIVED

PMID: 31198061 (View on PubMed)

Lee H, Mizrahi MA, Hartings JA, Sharma S, Pahren L, Ngwenya LB, Moseley BD, Privitera M, Tortella FC, Foreman B. Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury. Crit Care Med. 2019 Apr;47(4):574-582. doi: 10.1097/CCM.0000000000003639.

Reference Type: DERIVED

PMID: 30624278 (View on PubMed)

Related Links

http://www.neurenpharma.com

Click here for more information about this study

Other Identifiers

Neu-2566-TBI-001

Identifier Type: -

Identifier Source: org_study_id