Clinical Trial: Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients

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

Official Title: A Multi-Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome

Brief Summary: A study of ifetroban in the treatment of hepatorenal syndrome (HRS) in hospitalized adult patients to assess the safety and pharmacokinetics of 3 days of intravenous ifetroban.

Detailed Summary:
Sponsor: Cumberland Pharmaceuticals

Current Primary Outcome:

• Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide [ Time Frame: 3 days ]
  Plasma concentrations of ifetroban and its major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
• Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment [ Time Frame: 3 days ]
  Plasma concentrations of ifetroban and its primary active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
• Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment [ Time Frame: 3 days ]
  Plasma concentrations of ifetroban and it's major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.

Original Primary Outcome:

• Pharmacokinetic profile (Cmax, Cmin, Vdss, T1/2, AUC 0-24, and AUC 0-inf) of ifetroban and ifetroban acylglucuronide [ Time Frame: 5 days ]

  To evaluate the primary objective of determining the pharmacokinetic profile of multiple daily intravenous doses of ifetroban, the following endpoints will be measured:

  • Pharmacokinetic parameters, including serum concentration versus time profile of ifetroban and its major metabolite ifetroban acylglucuronide for the 24-hour period after the first dose, Cmax, Cmin, Vdss, T1/2, AUC 0-24 (area under the curve during 24 hours), and AUC 0-inf (area under the curve extrapolated to infinity), will be determined from analysis of collected blood samples.

• Vital signs, clinical chemistry, urine electrolytes, coagulation/hematology assessments, treatment emergent adverse events, and Day 28 mortality of ifetroban injection in patients with HRS. [ Time Frame: 28 days ]

  To evaluate the primary objective of determining the tolerability and safety of ifetroban injection in patients with HRS, the following endpoints will be measured:

  • Vital signs (heart rate, respiratory rate, blood pressure, temperature, pulse oximetry saturation)
  • Clinical chemistry, urine electrolytes, coagulation and hematology assessments
  • Treatment emergent adverse events
  • Day 28 mortality

Current Secondary Outcome:

• Safety: Day 28 Mortality [ Time Frame: 28 days ]
• Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL [ Time Frame: Day 0 through Day 5 ]
• The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements [ Time Frame: Day 0 to Day 5 ]
• Change in 24-hour Urine Volume [ Time Frame: Baseline to Hour 96 ]
  The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period.

Original Secondary Outcome: Serum creatinine, Creatinine clearance, BUN, urine output, estimated GFR, Urinary TxB2-M, and plasma F2-isoprostane levels of ifetroban injection in patients with HRS. [ Time Frame: Baseline and 5 days ]

Information By: Cumberland Pharmaceuticals

Dates:
Date Received: August 31, 2011
Date Started: October 2011
Date Completion:
Last Updated: February 27, 2017
Last Verified: February 2017