Study of NNZ-2566 in Patients With Traumatic Brain Injury

Brain Injuries Clinical Trial

— INTREPID2566  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of NNZ-2566 in Patients With Traumatic Brain Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00805818
• Other study ID #: Neu-2566-TBI-001
• Status: Completed
• Phase: Phase 2
• First received: December 8, 2008
• Last updated: February 1, 2018
• Start date: April 2010
• Est. completion date: January 2016

Study information

• Verified date: February 2018
• Source: Neuren Pharmaceuticals Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether NNZ-2566 is safe and effective in the treatment of Traumatic Brain Injury (TBI).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Wounds and Injuries

Intervention

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.
• Placebo
Sodium Chloride 0.9% Injection

Locations

Country	Name	City	State
United States	Our Lady of the Lake Hospital	Baton Rouge	Louisiana
United States	St Luke's University Hospital	Bethlehem	Pennsylvania
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	University of Cincinnati, Mayfield Clinic	Cincinnati	Ohio
United States	Arrowhead Regional Medical Center	Colton	California
United States	Miami Valley Hospital	Dayton	Ohio
United States	Detroit Receiving Hospital and University Health Center	Detroit	Michigan
United States	Sinai Grace Hospital	Detroit	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Texas Health Harris Methodist Hospital Fort Worth	Fort Worth	Texas
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Miami, Lois Pope Life Center	Miami	Florida
United States	University of Wisconsin, Froedtert Hospital	Milwaukee	Wisconsin
United States	University of South Alabama	Mobile	Alabama
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California, Davis Medical Center	Sacramento	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Neuren Pharmaceuticals Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs)		AEs to discharged or Day 30 post randomization, whichever occurs first, and SAEs through to 3 months (defined as 12-14 weeks), post randomization.
Secondary	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))		1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization.
Secondary	Improvement in cognitive and neuropsychological functioning.		1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization.
Secondary	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.		Baseline through to 72 hours post-start of infusion.
Secondary	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.		Start of infusion through to 12 hours post infusion.

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