A Safety and Efficacy Study of NNZ-2566 in Patients With Mild Traumatic Brain Injury (mTBI)
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|ClinicalTrials.gov Identifier: NCT02100150|
Recruitment Status : Terminated
First Posted : March 31, 2014
Last Update Posted : February 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Concussion||Drug: NNZ-2566 Drug: Placebo||Phase 2|
Traumatic brain injury (TBI) is an injury to the head caused by an external trauma that can lead to brain cell death, inflammation, edema, hemorrhage, and disruption of normal brain cell function. mTBI frequently results in persistent functional impairment including problems with cognitive function, memory, mood, and other personality disorders.
There are currently no drugs available to reduce the brain damage or sequelae that result from TBI. Clearly, a safe and effective treatment for concussion injury and all forms of TBI would be an important development for military personnel as well as the general population.
This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescents and adults with mTBI. The study also will also investigate measures of efficacy during treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of NNZ-2566 in the Acute Treatment of Adolescents and Adults With Mild Traumatic Brain Injury (mTBI)|
|Actual Study Start Date :||September 2014|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (3g in 30 milliliter vials) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.
Placebo Comparator: Placebo (strawberry flavored solution)
Strawberry flavored solution and water
Strawberry flavored solution 0.5% v/v in Water for Injection
Other Name: Strawberry flavored solution
- Cognitive Function - Automated Neuropsychological Assessment Metrics (ANAM) [ Time Frame: Through to Day 28 ]
The ANAM is a library of computerized tests that measures 6 cognitive domains believed to be most highly impacted by mTBI: simple reaction time, procedural reaction time, learning, working memory, delayed memory, and spatial memory.
Only selected subtests of the ANAM will be performed during this study, as follows:
- Code substitution - learning, simple reaction time, procedural reaction time, code substitution.
- Simple reaction time and procedural reaction time.
- General Clinical Status - Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I) [ Time Frame: Through to Day 28 ]The CGI-S is an assessment that requires the clinician to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis.
- Post-Injury Symptoms [ Time Frame: Through to Day 28 ]
Residual self-reported symptoms associated with mTBI will be assessed using the Post-Concussion Symptom Scale (PCSS).
The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is used to measure the presence and severity of post-concussion syndrome, which addresses a set of somatic, cognitive, and emotional symptoms following TBI.
- Postural Stability [ Time Frame: Through to Day 28. ]
Postural sway will be analysed using the Sway Balance Application. Sway Balance will be measured using the Balance Error Scoring System (BESS). Pupil size and dynamics as well as the associated neurological pupillary index (NPi) will be measured using a handheld, infrared, digital pupillometer.
An Accommodation/Convergence test will be performed. Convergence is the inward rotational ability of the eye. Accommodation is the ability of the eye to maintain focus as the distance changes.
- Psychological Sequelae [ Time Frame: Through to Day 28 ]
Anxiety and depression will be measured using the Hospital Anxiety and Depression Scale (HADS).
Post-traumatic stress disorder will be measured by the Post-Traumatic Stress Disorder Checklist-Specific (PCL-S).
- Change in subject's readiness and fitness to return to work as measured by the Return-to-Duty Assessment [ Time Frame: Day 3 to 28 ]The Return-to-Duty Assessment is a standardized protocol to determine a subject's readiness or fitness to return to duty (yes/no). Once the subject has been cleared to return to duty, this assessment is no longer applicable for that subject.
- Residual Functional Disability [ Time Frame: Day 28 ]Residual Functional Ability will be measured by the Sheehan Disability Scale (SDS) which measures the extent to which 3 major sectors in the subject's life are impaired by an illness or disorder.
- Safety [ Time Frame: Screening through to Day 28 or the final study visit, whichever comes later ]Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. Incidence of AEs and SAEs will be evaluated from randomized dosing through to Day 28 or the final study visit, whichever comes later.
- Pharmacodynamic Measurements of Protein Biomarkers and micro-RNA [ Time Frame: Screening through to Day 3 ]A blood sample will be obtained to measure levels of protein biomarkers (SBDP150, S100, GFAP, and UCH-L1) that are derived from the cytosol of neurons, astrocytes, axons; micro-RNA (mi-RNA) levels will also be measured. This blood sample will be obtained at Screening, and on Days 1, 2, and 3.
- Pharmacokinetic (PK) Measurements - maximum observed concentration (Cmax), trough concentration (Cmin),and area under the concentration-time curve (AUC) at steady-state [ Time Frame: Day 3 and Day 7 ]
The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax, Cmin, and AUC at steady-state.
A PK blood sample (2 x 2 mL) will be collected on Day 3 at approximately 2 to 4 hours after administration of study drug, and on Day 7 at pre-dose and approximately 4 hours after administration of study drug.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02100150
|United States, North Carolina|
|Fayetteville, North Carolina, United States, 28307|
|Principal Investigator:||Wesley R Cole, Ph.D||Fort Bragg|
|Principal Investigator:||Kurt Denninghoff, MD||University of Arizona|
|Principal Investigator:||Alex Hishaw, MD||University of Arizona|
|Principal Investigator:||Brian O'Neil, MD||Detroit Receiving Hospital|