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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Neuren Pharmaceuticals Limited
Sponsor:
Information provided by (Responsible Party):
Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier:
NCT01366820
First received: May 29, 2011
Last updated: February 10, 2014
Last verified: February 2014
  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: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Study of NNZ-2566 in Patients With Traumatic Brain Injury (TBI) Conducted Under an Exception From Informed Consent (EFIC)

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 ]

Estimated Enrollment: 200
Study Start Date: February 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NNZ-2566
20 mg/kg intravenous bolus infusion of NNZ-2566 over 10 minutes followed by a continuous intravenous infusion of 6 mg/kg/h (n=133) intravenous infusion of NNZ-2566 for a total of 72 consecutive hours.
Drug: NNZ-2566

Solution for intravenous infusion.

Intravenous bolus infusion over 10 minutes followed by a continuous intravenous maintenance infusion 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 of Sodium Chloride (0.9%) for Injection over 10 minutes followed by a continuous intravenous infusion of Sodium Chloride (0.9%) for Injection for a total of 72 consecutive hours.
Drug: NNZ-2566

Solution for intravenous infusion.

Intravenous bolus infusion over 10 minutes followed by a continuous intravenous maintenance infusion 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:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-penetrating TBI.
  • Age 16-75 years.
  • Admission to hospital.
  • Post resuscitation GCS 4-12.
  • Have at least one reactive pupil.
  • Able to receive investigational product within 8 hours of injury.
  • Hemodynamically stable after resuscitation (systolic blood pressure (SBP) >100 mm Hg).
  • Able to read and write English and have sufficient motor dexterity prior to injury to undertake the neuropsychological and activities of daily living (ADL) testing, in the opinion of the investigator, at 1 month (defined as 4-6 weeks) and 3 months (defined as 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 would, in the opinion of the Investigator, interfere with or bias the assessment of efficacy.
  • Significant non-central nervous system (CNS) injuries sustained at the time of the TBI would, in the opinion of the Investigator, 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 blood, colloid or crystalloid fluid resuscitation prior to randomization.
  • Pregnant or nursing mothers. Women of child-bearing potential must have a negative urine or blood test prior to randomization.
  • 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: NCT01366820

Contacts
Contact: James A Bonnar +64 21-631-969 jbonnar@neurenpharma.com

Locations
United States, California
Arrowhead Regional Medical Center Recruiting
Colton, California, United States, 92324
Contact: Javed Siddiqi, MD         
Principal Investigator: Javed Siddiqi, MD         
Sub-Investigator: Dan Miulli, DO         
Sub-Investigator: Rosalina Menoni, MD         
Sub-Investigator: Margaret Wacker, MD         
Sub-Investigator: Jamshid Mistry, DO         
Sub-Investigator: Deependra Mahato, DO         
Sub-Investigator: Blake Berman, DO         
Sub-Investigator: Quang Ma, DO         
Sub-Investigator: Jerry Noel, DO         
Sub-Investigator: Vladimir Cortez, DO         
Sub-Investigator: Zeyad Al Wahib, MD         
Sub-Investigator: Dennis Cramer, DO         
Sub-Investigator: Shahnawas Qureshi, DO         
Sub-Investigator: Fadi Andraos, MD         
Sub-Investigator: Katie Huynh, DO         
Sub-Investigator: Silvio Hoshek, MD         
Sub-Investigator: Adam Castorena         
University of California, Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Kiarash Shahlaie, MD         
Principal Investigator: Kiarash Shahlaie, MD         
Sub-Investigator: James Boggan, MD         
Sub-Investigator: Deborah Diercks, MD         
Sub-Investigator: Nancy Rudisill, RN, CCRP         
Sub-Investigator: Janice Wang-Polagruto, PhD, CCRP         
Sub-Investigator: Karen Smith, RN         
Sub-Investigator: Darrin Lee, MD         
Sub-Investigator: Joan Holmes-Asamoah, RN, FNP         
Sub-Investigator: Gilbert Cardena, MD         
Sub-Investigator: Christi DeLemos, RN MSN ACNP         
Sub-Investigator: Jonathan Liu, MD         
Sub-Investigator: Krista Keachie, MD         
Sub-Investigator: Edward Kerr, MD         
Sub-Investigator: Lori Madden, RN, MS, ACNP         
Sub-Investigator: Azeem Oladunjoye, MD         
Sub-Investigator: Jared Ament, MD         
United States, Hawaii
The Queen's Medical Center Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Cherylee WJ Chang, MD         
Principal Investigator: Cherylee WJ Chang, MD         
Sub-Investigator: Mathew A Koenig, MD         
Sub-Investigator: Daniel Donovan, MD         
Sub-Investigator: Kazuma Nakagawa, MD         
Sub-Investigator: Jan Kondo, Pharm D         
Sub-Investigator: Sharon Moran, MD         
Sub-Investigator: Caesar Ursic, MD         
Sub-Investigator: Tina Robertson, RN         
Sub-Investigator: Tracy Stern, RN         
Sub-Investigator: Susan Asai, RN         
Sub-Investigator: Jennifer Moran, APRN         
Sub-Investigator: Denise N Dittrich, RN         
United States, Michigan
Detroit Receiving Hospital and University Health Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Brian J O'Neill, MD         
Contact: Patrick Medado, BS, CCRP    313-745-4621    pbmedado@med.wayne.edu   
Principal Investigator: Brian O'Neil, MD         
Sub-Investigator: Phillip Levy, MD, MPH         
Sub-Investigator: Robert Sherwin, MD         
Sub-Investigator: Jonathan Sullivan, MD, PhD         
Sub-Investigator: Anthony Lagina, MD         
Sub-Investigator: Claire Pearson, MD, MPH         
Sub-Investigator: Marc Anthony Velilla, MD         
Sinai Grace Hospital Recruiting
Detroit, Michigan, United States, 48235
Contact: Marc Anthony Velillia, MD    313-966-9489    mvelilla@dmc.org   
Contact: Duane Robinson    313-745-4347    drobinso@med.wayne.edu   
Principal Investigator: Brian O'Neil, MD         
Sub-Investigator: Angela K Groves, MD         
Sub-Investigator: Brian J O'Neil, MD         
Sub-Investigator: Robert Welch, MD         
Sub-Investigator: Robert Sherwin, MD         
Sub-Investigator: Claire Pearson, MD         
Sub-Investigator: Floyd Vitale, RPh         
Sub-Investigator: Marc Anthony Velillia, MD         
United States, Pennsylvania
University of Pennsylvania Withdrawn
Philadelphia, Pennsylvania, United States, 19104-6205
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: David Okonkwo, MD         
Principal Investigator: David Okonkwo, MD         
Sub-Investigator: Richard Spiro, MD         
Sub-Investigator: Ava Puccio, RN, PhD         
Sponsors and Collaborators
Neuren Pharmaceuticals Limited
Investigators
Principal Investigator: Ross R Bullock, M.D., PhD University of Miami, Lois Pope Life Center
  More Information

No publications provided

Responsible Party: Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT01366820     History of Changes
Other Study ID Numbers: Neu-2566-TBI-002
Study First Received: May 29, 2011
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 20, 2014