Concussion
Conditions
Keywords
Concussion
Brief summary
The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of mTBI in adolescents and adults.
Detailed description
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.
Interventions
DRUGNNZ-2566
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.
DRUGPlacebo
Strawberry flavored solution 0.5% v/v in Water for Injection
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has a diagnosis of mTBI resulting from an injury that meets the following criteria: 1. Occurred within 24 hours of Screening and was associated with a clear mechanism of injury and an alteration of consciousness (e.g., confusion, feeling dazed, or seeing stars) 2. Was associated with a GCS score of 13-15 3. Was associated with 1 or more of the following signs and symptoms, as determined by a qualified clinician: i. Headache ii. Loss of consciousness iii. Post traumatic amnesia iv. Retrograde amnesia v. Difficulty concentrating vi. Balance problems vii. Dizziness viii. Visual problems ix. Personality changes x. Fatigue xi. Sensitivity to light/noise xii. Numbness xiii. Nausea xiv. Vomiting d. Current symptoms associated with the mTBI are causing clinically significant impairment 2. Subject is 16 to 55 years old. 3. Subject has a CGI-S score of ≥3 at Screening 4. Subject has an RPQ-3 score of ≥3 at Screening 5. Subjects who are taking psychotropic medications must have been receiving a stable regimen (i.e., same dosage and regimen) for at least 4 weeks prior to Screening. For the purposes of this protocol, psychotropic medications are defined as medications that are prescribed for intended CNS benefits. Medications for headache are permissible, as needed, according to approved prescribing information. 6. Women of child-bearing potential must have a negative urine pregnancy test at Screening. Men and women must agree to use a contraceptive method with \<1% success rate (e.g., oral contraceptive, injectable progestogen, levonorgestrel implant, estrogenic vaginal ring, percutaneous contraceptive patch, intrauterine device \[IUD\], surgical sterilization, or double barrier method \[i.e., condom with diaphragm or spermicidal agent\]).
Exclusion criteria
Subjects are ineligible for the study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual Functional Disability | 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. |
| Postural Stability | 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 | 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 | 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. |
| Cognitive Function - Automated Neuropsychological Assessment Metrics (ANAM) | 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) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Measurements of Protein Biomarkers and micro-RNA | 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 | 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. |
| Safety | 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. |
Countries
United States
Outcome results
None listed