NCT00805818

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
261

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2010

Longer than P75 for phase_2

Geographic Reach
1 country

20 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 8, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 10, 2008

Completed
1.3 years until next milestone

Study Start

First participant enrolled

April 1, 2010

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

February 5, 2018

Status Verified

February 1, 2018

Enrollment Period

5.8 years

First QC Date

December 8, 2008

Last Update Submit

February 1, 2018

Conditions

Brain Injuries

Outcome Measures

Primary Outcomes (1)

  • Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs)

    AEs to discharged or Day 30 post randomization, whichever occurs first, and SAEs through to 3 months (defined as 12-14 weeks), post randomization.

Secondary Outcomes (4)

  • Evidence of efficacy in modifying global outcomes by evaluating Glasgow Outcome Scale - Extended (GOS-E) and activities of daily living (Mayo-Portland Adaptability Inventory - 4th Edition (MPAI-4))

    1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization.

  • Improvement in cognitive and neuropsychological functioning.

    1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization.

  • Modification of the acute physiological processes in TBI by evaluating electroencephalographic (EEG) determinants in patients with moderate to severe TBI (defined as GCS 4-12), and biomarker levels.

    Baseline through to 72 hours post-start of infusion.

  • Blood pharmacokinetics (PK) of an intravenous (i.v) dose of NNZ-2566 when administered as a 10-minute infusion immediately followed by a 72-hour infusion.

    Start of infusion through to 12 hours post infusion.

Study Arms (2)

NNZ-2566

EXPERIMENTAL

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.

Drug: NNZ-2566

Sodium Chloride (0.9%) for Injection

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

NNZ-2566DRUG

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.

Also known as: Glycyl-L-2-Methylprolyl-L-Glutamic Acid
NNZ-2566
PlaceboDRUG

Sodium Chloride 0.9% Injection

Also known as: Sodium Chloride 0.9% Injection
Sodium Chloride (0.9%) for Injection

Eligibility Criteria

Age18 Years - 70 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

University of South Alabama

Mobile, Alabama, 36617, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Arrowhead Regional Medical Center

Colton, California, 92324, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Miami, Lois Pope Life Center

Miami, Florida, 33136, United States

Location

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Our Lady of the Lake Hospital

Baton Rouge, Louisiana, 70808, United States

Location

Detroit Receiving Hospital and University Health Center

Detroit, Michigan, 48201, United States

Location

Sinai Grace Hospital

Detroit, Michigan, 48235, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of Cincinnati, Mayfield Clinic

Cincinnati, Ohio, 45219, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

St Luke's University Hospital

Bethlehem, Pennsylvania, 18015, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Texas Health Harris Methodist Hospital Fort Worth

Fort Worth, Texas, 76104, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Charleston Area Medical Center

Charleston, West Virginia, 25304, United States

Location

University of Wisconsin, Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

  • 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.

    PMID: 31198061DERIVED

  • 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.

    PMID: 30624278DERIVED

Related Links

MeSH Terms

Conditions

Brain Injuries

Interventions

trofinetideSodium Chloride

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Ross R Bullock, M.D., PhD

    University of Miami, Lois Pope Life Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

December 8, 2008

First Posted

December 10, 2008

Study Start

April 1, 2010

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

February 5, 2018

Record last verified: 2018-02

Data Sharing

IPD Sharing
Will not share

Locations

US(20)