Study of NNZ-2566 in Patients With Traumatic Brain Injury (INTREPID2566)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier:
NCT00805818
First received: December 8, 2008
Last updated: March 21, 2016
Last verified: March 2016
  Purpose
The purpose of this study is to determine whether NNZ-2566 is safe and effective in the treatment of Traumatic Brain Injury (TBI).

Condition Intervention Phase
Brain Injuries
Drug: NNZ-2566
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of NNZ-2566 in Patients With Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Neuren Pharmaceuticals Limited:

Primary Outcome Measures:
  • Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: AEs to discharged or Day 30 post randomization, whichever occurs first, and SAEs through to 3 months (defined as 12-14 weeks), post randomization. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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)) [ Time Frame: 1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization. ] [ Designated as safety issue: No ]
  • Improvement in cognitive and neuropsychological functioning. [ Time Frame: 1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization. ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Baseline through to 72 hours post-start of infusion. ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Start of infusion through to 12 hours post infusion. ] [ Designated as safety issue: Yes ]

Enrollment: 261
Study Start Date: April 2010
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.

Other Name: Glycyl-L-2-Methylprolyl-L-Glutamic Acid
Placebo Comparator: 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.
Drug: 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.

Other Name: Glycyl-L-2-Methylprolyl-L-Glutamic Acid

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.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  • QTc Exclusions. The study will use the exclusion criteria as defined in ICH Guideline E14 to exclude patients with a risk of QT/QTc prolongation, as follows:

    • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805818

Locations
United States, Alabama
University of South Alabama
Mobile, Alabama, United States, 36617
United States, Arizona
University of Arizona
Tuscon, Arizona, United States, 85724
United States, California
Arrowhead Regional Medical Center
Colton, California, United States, 92324
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
University of California, Davis Medical Center
Sacramento, California, United States, 95817
United States, Florida
University of Miami, Lois Pope Life Center
Miami, Florida, United States, 33136
United States, Hawaii
The Queen's Medical Center
Honolulu, Hawaii, United States, 96813
United States, Louisiana
Our Lady of the Lake Hospital
Baton Rouge, Louisiana, United States, 70808
United States, Michigan
Detroit Receiving Hospital and University Health Center
Detroit, Michigan, United States, 48201
Sinai Grace Hospital
Detroit, Michigan, United States, 48235
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
United States, New York
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, Ohio
University of Cincinnati, Mayfield Clinic
Cincinnati, Ohio, United States, 45219
Miami Valley Hospital
Dayton, Ohio, United States, 45409
United States, Pennsylvania
St Luke's University Hospital
Bethlehem, Pennsylvania, United States, 18015
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Parkland Hospital
Dallas, Texas, United States, 75235
Texas Health Harris Methodist Hospital Fort Worth
Fort Worth, Texas, United States, 76104
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
United States, West Virginia
Charleston Area Medical Center
Charleston, West Virginia, United States, 25304
United States, Wisconsin
University of Wisconsin, Froedtert Hospital
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Neuren Pharmaceuticals Limited
Investigators
Principal Investigator: Ross R Bullock, M.D., PhD University of Miami, Lois Pope Life Center
  More Information

Additional Information:
Responsible Party: Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT00805818     History of Changes
Other Study ID Numbers: Neu-2566-TBI-001 
Study First Received: December 8, 2008
Last Updated: March 21, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on May 03, 2016