A Safety and Efficacy Study of NNZ-2566 in Patients With Mild Traumatic Brain Injury (mTBI)
A Safety and Efficacy Study of NNZ-2566 in Patients With Mild Traumatic Brain Injury (mTBI)
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.
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.
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 exclusion criteria:

 1. Subject has a history of brain surgery or prior severe TBI (based on a previously
 documented GCS score of ≤8).

 2. Subject has a history of seizure disorder or has experienced seizures in the 24 hours
 preceding Screening. Note: Isolated febrile seizures during early childhood are not
 exclusionary.

 3. Subject has a history of diabetes mellitus requiring pharmacotherapy within the
 preceding 12 months.

 4. Subject has a history of hypothyroidism within the 3 years preceding Screening that
 currently requires or did require pharmacotherapy.

 5. Subject has regularly used more than 1 of the following psychoactive medications in
 the 4 weeks preceding Screening: methylphenidate, dextroamphetamine, mixed amphetamine
 salts, amantadine, memantine, cholinesterase inhibitors, modafinil, or armodafinil.

 6. Subject has a history of substance abuse or dependence, other than nicotine
 dependence, within the 3 months preceding Screening.

 7. Subject has signs/symptoms of acute impairment due to alcohol use.

 8. Subject has used anti-epileptic medications in the 4 weeks preceding Screening.

 9. Subject has used bromocryptine, levodopa, ropinirole, or pramipexole in the 4 weeks
 preceding Screening.

 10. Subject has a history of a major psychiatric disorder (including major depression, a
 clinically significant anxiety disorder, or a psychotic disorder) that is associated
 with significant clinical impairment within the preceding 6 months.

 11. In the Investigator's opinion, the subject poses a current homicidal or serious
 suicidal risk, and/or has made a suicide attempt within the 6 months preceding
 Screening.

 12. Subject has a neurological disorder other than mTBI (e.g., Parkinson's disease,
 stroke, multiple sclerosis, dementia, delirium, infectious encephalopathy) that has
 required treatment within the 6 months preceding Screening.

 13. Subject has a history of, or current, cerebrovascular disease.

 14. Subject has a history of, or current, malignancy.

 15. Subject has an unstable medical disorder that may pose a safety concern or interfere
 with the accurate assessment of safety or efficacy.

 16. Subject has laboratory values at Screening deemed to be clinically significant by the
 Investigator.

 17. Subject has an average QT interval corrected using Fridericia's formula (QTcF) >450
 msec at Screening or any ECG abnormality that may pose a potential safety concern.

 18. Subject has a history of risk factors for torsade de pointes (e.g., heart failure,
 clinically significant hypokalemia, a serum potassium value at Screening of <3.0
 mmol/L, or a family history of long QT syndrome).

 19. Subject has a history of QT/QTcF prolongation previously or currently controlled with
 medication, in which normal QT/QTcF intervals could or can only be achieved with
 medication.

 20. Subject has participated in another clinical treatment study within the 4 weeks
 preceding Screening.

 21. Subject is unable to provide informed consent (where deemed cognitively able by
 standard assessments) or informed consent cannot be obtained from a legally authorized
 individual (e.g., spouse, or in the instance of minors, a parent).

 22. Subject is pregnant or nursing.

 23. Subject was previously enrolled in this study.

 24. Subject has an allergy to strawberries.