Study of NNZ-2566 in Patients With Traumatic Brain Injury - Full Text View

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:

MedlinePlus related topics: Traumatic Brain Injury

U.S. FDA Resources

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:	260
Study Start Date:	April 2010
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	November 2013 (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

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

Contacts

Contact: Maria Simula	+61 413-688-748	msimula@neurenpharma.com
Contact: Maggie Scott	+64 21-638-990	mscott@neurenpharma.com

Locations

United States, California
Arrowhead Regional Medical Center	Recruiting
Colton, California, United States, 92324
Contact: Javed Siddiqi, MD 909-580-1366 siddiqij@armc.sbcounty.gov
Contact: Fadi Andraos 909-580-1366 andraosf@armc.sbcounty.gov
Principal Investigator: Javid Siddiqi, MD
Sub-Investigator: Dan Miulli, DO
Sub-Investigator: Silvio Hoshek, MD
Sub-Investigator: Dennis Cramer, DO
Sub-Investigator: John Capua, DO
Sub-Investigator: Jamshid Mistry, DO
Sub-Investigator: Deependra Mahato, DO
Sub-Investigator: Jerry Noel, DO
Sub-Investigator: Quang Ma, DO
Sub-Investigator: Blake Berman, DO
Sub-Investigator: Shahnawaz Qureshi, DO
Sub-Investigator: Katie Huynh, DO
Sub-Investigator: Fadi Andraos, MD
Sub-Investigator: Susannah Oh, DO
Ronald Reagan UCLA Medical Center	Terminated
Los Angeles, California, United States, 90095
Riverside County Regional Medical Center	Not yet recruiting
Moreno Valley, California, United States, 92555
Contact: Javed Siddiqi, MD, PhD jsiddiqi@co.riverside.ca.us
Contact: Fadi Andraos, MD andraosf@armc.sbcounty.gov
Principal Investigator: Javed Sidiqqi, MD, PhD
University of California, Davis Medical Center	Recruiting
Sacramento, California, United States, 95817
Contact: Kiarash Shahlaie, MD 916-734-3071 krshahlaie@ucdavis.edu
Contact: Nancy Rudisill, RN, MSN 916-734-3491 nancy.rudisill@ucdmc.ucdavis.edu
Principal Investigator: Kiarash Shahlaie, MD, PhD
Sub-Investigator: Deborah Diercks, MD
Sub-Investigator: Nancy Rudisill, RN, MSN
Sub-Investigator: Janice Wang-Polagruto, PhD, CCRP
Sub-Investigator: Lori Madden, RN, MS, ACNP
Sub-Investigator: Karen Smith, RN
Sub-Investigator: Christi DeLemos, RN MSN ACNP
Sub-Investigator: Joan Holmes-Asamoah, RN, FNP
Sub-Investigator: Edward Kerr, MD
Sub-Investigator: Azeem Oladunjoye, MD
Sub-Investigator: Darrin Lee, MD
Sub-Investigator: Gilbert Cadena, MD
Sub-Investigator: Jonathan Liu, MD
Sub-Investigator: Krista Keachie, MD
Sub-Investigator: James Boggan, MD
United States, Connecticut
Hartford Hospital	Withdrawn
Hartford, Connecticut, United States, 06102
United States, Florida
University of Miami, Lois Pope Life Center	Recruiting
Miami, Florida, United States, 33136
Contact: Ross M Bullock, MB PhD 305-243-4456 rbullock@med.miami.edu
Contact: Zsuzsanna Nemith, BS, CCRC 305-243-3056 znemeth@med.miami.edu
Principal Investigator: Ross M Bullock, MD, PhD
Sub-Investigator: Jonathan Jagid, MD
United States, Hawaii
The Queen's Medical Center	Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Cherylee WJ Chang, MD 808-691-7152 cchang@queens.org
Contact: Tracy Stern, RN 808-691-7175 tstern@queens.org
Principal Investigator: Cherylee WJ Chang, MD
Sub-Investigator: Matthew Koenig, MD
Sub-Investigator: Daniel Donovan, MD
Sub-Investigator: Tracy Stern, RN
Sub-Investigator: Susan Asai, RN
Sub-Investigator: Jennifer Moran, APRN
Sub-Investigator: Kazuma Nakagawa, MD
Sub-Investigator: Sharon Moran, MD
Sub-Investigator: Caesar Ursic, MD
Sub-Investigator: Jan Kondo, PharmD
Sub-Investigator: Tina Robertson, RN
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'Neil, MD 313-993-2530 boneil@med.wayne.edu
Contact: Patrick Medado, BS, CCRP 313-745-4621 pbmedado@med.wayne.edu
Principal Investigator: Brian J 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
Sub-Investigator: Robert Welch, MD
Sinai Grace Hospital	Recruiting
Detroit, Michigan, United States, 48235
Contact: Marc Anthony Velilla, MD 313-966-1020 mvelilla@dmc.org
Contact: Duane Robinson 313-745-4347 drobinso@med.wayne.edu
Principal Investigator: Marc Anthony Velilla, MD
Sub-Investigator: Angela Groves, MD
Sub-Investigator: Brian O'Neil, MD
Sub-Investigator: Robert Welch, MD
Sub-Investigator: Robert Sherwin, MD
Sub-Investigator: Claire Pearson, MD
Sub-Investigator: Floyd Vitale, RPh
United States, New York
SUNY Upstate Medical University	Terminated
Syracuse, New York, United States, 13210
United States, Ohio
Aultman Hospital	Not yet recruiting
Canton, Ohio, United States, 44710
Contact: Mark Marchetta, RN 330-363-6186 mmarchetta@aultman.com
Contact: Lisa Mittas, RN 330-363-3079 lmittas@aultman.com
Principal Investigator: Steven Kelly, 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 O Okonkwo, MD 412-647-2772 okonkwodo@upmc.edu
Contact: Ava Puccio, RN, PhD +1-412-648-9246 puccam@upmc.edu
Principal Investigator: David O Okonkwo, MD
Sub-Investigator: Richard Spiro, MD
Sub-Investigator: Ava Puccio, RN, PhD
United States, Texas
Texas Health Harris Methodist Hospital Fort Worth	Not yet recruiting
Fort Worth, Texas, United States, 76104
Contact: Cathy Dykes 817-250-7860 CathyDykes@texashealth.org
Principal Investigator: William Witham, MD
United States, Virginia
Inova Fairfax Hospital	Terminated
Falls Church, Virginia, United States, 22042
United States, West Virginia
Charleston Area Medical Center	Terminated
Charleston, West Virginia, United States, 25304

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:

Click here for more information about this study This link exits the ClinicalTrials.gov site

No publications provided

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:	May 7, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on May 19, 2013

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