Clinical Trial: A Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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)

Brief Summary:

The purpose of the first part of this study is 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.

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.


Detailed Summary:

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.

Part 2 of the study will be a multicenter, double blind, placebo-controlled study in trauma patients with hemorrhagic shock who are able to give consent or severe trauma patients with hemorrhagic shock in whom a legally authorized representative can give consent. 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.


Sponsor: Dr. Hasan Alam

Current Primary Outcome: Dose limiting toxicity (DLT) [ Time Frame: Subjects will be monitored for 4 days after the one hour infusion. Dose escalation may occur if less than 2 subjects in any cohort of 8 experience DLT. ]

Dose limiting toxicity (DLT) will be defined as drug-related grade 2 (moderate) or higher toxicity (excluding fever, chills, nausea or other possible infusion-related effects). The maximum tolerated dose (MTD) will be declared at the dose below which 2 or more subjects experience DLT.


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Michigan

Dates:
Date Received: September 23, 2013
Date Started: September 2013
Date Completion:
Last Updated: December 16, 2016
Last Verified: December 2016