Multicenter, Double-blind, Randomized, Placebo Controlled, Study to Assess the Safety of Amantadine Hydrochloride (HCl) Intravenous (IV) Solution (MR-301), in Patients With Severe Traumatic Brain Injury (TBI).
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 45
- 试验地点
- 13
- 主要终点
- Frequency, severity, and type of adverse events and serious adverse events between active treatment and placebo groups
研究概览
简要总结
The main goal of this clinical trial is to check if the treatment is safe and well-tolerated. Researchers will compare the MR-301 active drug group with the placebo group to evaluate the safety and tolerability of the drug. Other measurements include assessing the patient's overall outcome, neurological responses, time spent in the intensive care unit, time in the hospital, and mortality. Participants will receive either MR-301 BID IV dosing or a matching placebo for a total of 3 weeks.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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) ≤
- •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)].
排除标准
- •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.
研究组 & 干预措施
MR-301
On first day, patient will receive MR-301 at 100 mg intravenous infusion BID. On second day, the dose is elevated to 150 mg intravenous infusion BID.
On third day, the dose is further elevated to 200 mg intravenous infusion BID and maintained up to Day 21
干预措施: Amantadine Hydrochloride (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency, severity, and type of adverse events and serious adverse events between active treatment and placebo groups
时间窗: Day 1 to Day 35
Safety and tolerability will be compared between active treatment and placebo groups.
次要结局
- Change from baseline in Disability Rating Scale (DRS) scale(Day 5, Day 10, Day 15, Day 21)
- Change from baseline in Full Outline of UnResponsiveness (FOUR) score(every day up to Day 21)
- Time to intensive care unit (ICU) discharge to hospital floor(up to day 21)
- Mortality assessment at end of study period (Day 35).(Day 35)
- Change from baseline in Coma Recovery Scale - Revised(Day 5, Day 10, Day 15, Day 21)
- Mortality assessment at end of treatment period(Day 21)
- Change from baseline in Glasgow Outcome Scale-Extended(Day 21 and Day 35)
- Time to hospital discharge from randomization(up to day 21)