Study to Assess the Safety of Amantadine Hydrochloride (HCl) Intravenous (IV) Solution (MR-301) in Patients With Severe Traumatic Brain Injury (TBI).

Eligibility Criteria

• 1. Age: 18 to 75 years.
• 2. Patients with TBI confirmed by CT scan or MRI
• 3. Patient have sustained a trauma between 72 hours to 1 week
• 4. Patient with Abbreviated Injury Score (AIS) ≤ 2.
• 5. Patients must be admitted to an acute care setting no less than 2 days prior to randomization.
• 6. Glasgow Coma Score of 3 to 8, inclusive.
• 7. Patients must be unable to consistently follow commands or to engage in functional communication, as assessed by the score on the CRS-R.
• 8. Patients have at least one reactive pupil.
• 9. Must have a Legally Authorized Representative (LAR) able to provide consent for the trial.
• 10. Patient must have stable vitals ---Intracranial pressure ICP Value is at discretion of investigator), systolic blood pressure (SBP\>90 mmHg) partial pressure of oxygen (PaO2 \> 60 mmHg)\].
• 1. Life expectancy of less than 24 hours.
• 2. Patient has any spinal cord injury.
• 3. Patient has a penetrating head injury.
• 4. Patient has bilaterally fixed dilated pupils
• 5. Patients with history of any medical or psychiatric disorder, or any severe concomitant disease that would, in the opinion of the Investigator, interfere with clinical assessment.
• 6. Patient has poorly controlled seizure more than one per month.
• 7. Prior history of status epilepticus
• 8. Prior treatment with or a sensitivity to amantadine HCl or amantadine.
• 9. Patient has screening lab measurements outside the normal range
• 1. Absolute neutrophil count (ANC): ≤ 1.5 x 109/L
• 2. Hemoglobin ≤ 8 g/dL or active bleeding requiring ongoing transfusions.
• 3. Platelets ≤ 80 x 109/L or active bleeding requiring ongoing transfusions.
• 4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) or total bilirubin (unless isolated Gilbert's syndrome) ≥ 2x the upper limit of normal (ULN)
• 5. Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2
• 10. Patient has received treatment with an investigational drug, CNS stimulant or dopamine antagonist/agonist within 4 weeks.
• 11. Patient has a history of NYHA Class 3 or Class 4 Congestive Heart Failure within the last 5 years.
• 12. Females who are nursing, pregnant, or planning to become pregnant
• 13. any other clinically significant medical condition as determined by the Investigator, that may unfavorably alter the risk benefit of study participation.
• 14. Patient has prolonged QT interval.
• 15. Treatment with a systemic anticholinergic medication within 1 week prior to screening.