Study of NNZ-2566 in Patients With Traumatic Brain Injury Under EFIC - 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: 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:

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:	200
Study Start Date:	February 2013
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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01366820

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
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	Not yet 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	Not yet 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	Not yet 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: Marc Anthony Velilla, 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
United States, Pennsylvania
University of Pennsylvania	Withdrawn
Philadelphia, Pennsylvania, United States, 19104-6205
University of Pittsburgh Medical Center	Not yet 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:	May 6, 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 Under EFIC (INTREPID2566)