A Phase 1, Single Ascending Dose, Double Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1) or Trauma Patients(Part 2)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
THIS IS THE SECOND PART OF A 2-PART STUDY. The purpose of the first part of this study was to determine the safety and tolerability of ascending doses of valproic acid (also known as Depacon) administered as intravenous infusion (IV) in doses ranging from 15 mg/kg to 250 mg/kg in healthy subjects.
ID: VPA-C-002
The second part of the study will also be to determine the safety and tolerability of single ascending doses of valproic acid administered as IV in trauma subjects with hemorrhagic shock.
详细描述
THIS IS THE SECOND PART OF A 2-PART STUDY. Part 1 of the study will be a single center study intended to assess the safety and tolerability of valproic acid dosages at 15 mg/kg, 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, 150 mg/kg 180 mg/kg, 210 mg/kg and 250 mg/kg. Up to 72 healthy subjects (9 dose groups of 8 subjects) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 3:1 active drug: placebo. ID: VPA-C-002
Part 2 of the study will be a multi-center, double blind, placebo-controlled study in trauma patients with hemorrhagic shock. The patients will be able to consent themselves, or if unable due to injuries, a Legally Authorized Representative will consent for them. Up to 12 patients (2 dose groups of 6 patients) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 2:1 active drug : placebo. The dose levels in Part 2 will be the two highest doses that are demonstrated to have acceptable safety profile based on the review of safety data from Part 1 (130mg/kg and 140mg/kg).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and non-pregnant female trauma patients between the ages of 18-70 years, inclusive.
- •Blunt or penetrating trauma resulting in two or more systolic blood pressure readings of ≤ 110 mmHg at any point during transport to the hospital or within the first hour after arrival in the emergency department. Systolic blood pressure readings of ≤ 110 mmHg need not be consecutive (Eastridge et al., 2007).
- •Patient's admission to the emergency department results in trauma team activation (per institutional criteria, see Appendix 7).
- •Patient's injuries are considered potentially survivable by the attending trauma surgeon on initial evaluation.
- •Able to provide informed consent or consent can be obtained from a representative (spouse or other legally authorized representative) in the event that the subject is unconscious or otherwise impaired.
- •Female subjects must be postmenopausal, surgically sterilized, or have a negative urinary pregnancy test on arrival. Criteria for menopause include age > 45 with absence of menses for > 12 months. Criteria for surgical sterilization include hysterectomy and/or oophorectomy. Tubal ligation with menses within the past 12 months is not considered to be surgical sterilization.
- •Body mass index (BMI) between 18 kg/m2 and 35 kg/m2
排除标准
- •Subjects with known history of adverse reaction to Valproic acid.
- •Subjects with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency.
- •Subjects with -amylase >400 U/L or lipase >300 U/L or creatinine >ULN
- •Subjects with AST or ALT >3X Upper limit of normal (ULN) or total bilirubin >1.5X Upper limit of normal (ULN)
- •Subjects with 2nd or 3rd degree burns of any size and location.
- •Female subjects who are pregnant or lactating.
- •Subjects who are currently incarcerated.
- •Subjects with severe traumatic brain injury (with Glasgow Coma Scale score <8 on arrival to the emergency department).
- •Non-hemorrhagic causes of shock, including septic, cardiogenic, or neurogenic shock or mechanical reasons such as tension pneumothorax or cardiac temponade.
- •Subjects with inadequate venous access.
- •Subject with a hemoglobin level of less than 8g/dL.
研究组 & 干预措施
Valproic acid (Depacon)
Valproic acid by IV infusion over one hour
干预措施: Valproic Acid (Drug)
Isotonic saline solution
The placebo administered by IV infusion over 1 hour
干预措施: Isotonic saline solution (Drug)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: As this is a safety study, subjects will be monitored for side-effects beginning immediately after the one hour infusion until the follow-up visit (between 2-6 weeks post infusion) is completed.
Dose limiting toxicity (DLT) will be measured by drug-related grade 2 (moderate) or higher toxicity indicators (excluding fever, chills, nausea or other possible infusion-related effects).
次要结局
未报告次要终点
研究者
Dr. Hasan Alam
Hasan Alam, MD, Norman Thompson Professor of Surgery Section Head, General Surgery
University of Michigan