Clinical trial NCT00805818: Study of NNZ-2566 in Patients With Traumatic Brain Injury
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of NNZ-2566 in Patients With Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Injuries
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2008-12-10
Enrollment: 261
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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).

Primary outcomes:
measure: Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 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 outcomes:
measure: 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))
timeFrame: 1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization.
measure: Improvement in cognitive and neuropsychological functioning.
timeFrame: 1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization.
measure: 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.
timeFrame: Baseline through to 72 hours post-start of infusion.
measure: 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.
timeFrame: Start of infusion through to 12 hours post infusion.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Colton
country: United States
facility: Arrowhead Regional Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Miami
country: United States
facility: University of Miami, Lois Pope Life Center
state: Florida
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Hospital
state: Louisiana
city: Detroit
country: United States
facility: Detroit Receiving Hospital and University Health Center
state: Michigan
city: Detroit
country: United States
facility: Sinai Grace Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati, Mayfield Clinic
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Bethlehem
country: United States
facility: St Luke's University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Fort Worth
country: United States
facility: Texas Health Harris Methodist Hospital Fort Worth
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Milwaukee
country: United States
facility: University of Wisconsin, Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: University of Miami, Lois Pope Life Center
name: Ross R Bullock, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee JW. The EEG Ictal-Interictal Continuum-A Metabolic Roar But a Whimper of a Functional Outcome. Epilepsy Curr. 2019 Jul-Aug;19(4):234-236. doi: 10.1177/1535759719855968. Epub 2019 Jun 14.
citation: Lee H, Mizrahi MA, Hartings JA, Sharma S, Pahren L, Ngwenya LB, Moseley BD, Privitera M, Tortella FC, Foreman B. Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury. Crit Care Med. 2019 Apr;47(4):574-582. doi: 10.1097/CCM.0000000000003639.