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

This is a multi-center, randomized, placebo-controlled study of MR-301 administered BID IV in patients with severe TBI.

Participant: 45 patients with severe TBI who maintain GCS scores 3-8 both inclusive.

Intervention: Mr-301 or placebo will be administered intravenously BID for upto 3 weeks.

Primary Outcome: Safety and Tolerability of MR-301

Secondary Outcome: GOS-E, CRS-R, DRS, FOUR score, time to ICU discharge, time to hospital discharge and mortality.

Inclusion criteria

• Age: 18 to 75 years.
• Patients with TBI confirmed by CT scan or MRI
• Patient have sustained a trauma between 72 hours to 1 week
• Patient with Abbreviated Injury Score (AIS) ≤ 2.
• Patients must be admitted to an acute care setting no less than 2 days prior to randomization.
• Glasgow Coma Score of 3 to 8, inclusive.
• Patients must be unable to consistently follow commands or to engage in functional communication, as assessed by the score on the CRS-R.
• Patients have at least one reactive pupil.
• Must have a Legally Authorized Representative (LAR) able to provide consent for the trial.
• 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)].

Exclusion criteria

• Life expectancy of less than 24 hours.
• Patient has any spinal cord injury.
• Patient has a penetrating head injury.
• Patient has bilaterally fixed dilated pupils
• 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.
• Patient has poorly controlled seizure more than one per month.
• Prior history of status epilepticus
• Prior treatment with or a sensitivity to amantadine HCl or amantadine.
• Patient has screening lab measurements outside the normal range

• Absolute neutrophil count (ANC): ≤ 1.5 x 109/L
• Hemoglobin ≤ 8 g/dL or active bleeding requiring ongoing transfusions.
• Platelets ≤ 80 x 109/L or active bleeding requiring ongoing transfusions.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) or total bilirubin (unless isolated Gilbert's syndrome) ≥ 2x the upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2
• Patient has received treatment with an investigational drug, CNS stimulant or dopamine antagonist/agonist within 4 weeks.
• Patient has a history of NYHA Class 3 or Class 4 Congestive Heart Failure within the last 5 years.
• Females who are nursing, pregnant, or planning to become pregnant
• any other clinically significant medical condition as determined by the Investigator, that may unfavorably alter the risk benefit of study participation.
• Patient has prolonged QT interval.
• Treatment with a systemic anticholinergic medication within 1 week prior to screening.