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

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ClinicalTrials.gov Identifier: NCT00805818
Recruitment Status : Completed
First Posted : December 10, 2008
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Neuren Pharmaceuticals Limited

Tracking Information
First Submitted Date  ICMJE December 8, 2008
First Posted Date  ICMJE December 10, 2008
Last Update Posted Date February 5, 2018
Study Start Date  ICMJE April 2010
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2008)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2008)
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of NNZ-2566 in Patients With Traumatic Brain Injury
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of NNZ-2566 in Patients With Traumatic Brain Injury
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Brain Injuries
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Sodium Chloride 0.9% Injection
    Other Name: Sodium Chloride 0.9% Injection
Study Arms  ICMJE
  • 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.
    Intervention: Drug: NNZ-2566
  • 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.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2016)
261
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2008)
260
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00805818
Other Study ID Numbers  ICMJE Neu-2566-TBI-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Neuren Pharmaceuticals Limited
Study Sponsor  ICMJE Neuren Pharmaceuticals Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ross R Bullock, M.D., PhD University of Miami, Lois Pope Life Center
PRS Account Neuren Pharmaceuticals Limited
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP