Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF
- Conditions
- Acute on Chronic Hepatic FailureLiver CirrhosisAcute Alcoholic HepatitisAcute Liver Failure
- Interventions
- Other: Placebo
- Registration Number
- NCT01937130
- Lead Sponsor
- Conatus Pharmaceuticals Inc.
- Brief Summary
The study will evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of IDN-6556 in subjects with cirrhosis of the liver who are hospitalized for more than 24 hours due to acute deterioration of liver function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 23
-
Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the study
-
Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis
-
Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis
-
Subjects with an acute deterioration of liver function
-
Subjects who meet one of the following criteria:
- Subjects with renal failure (defined as creatinine ≥ 2.0 to ≤ 3.4 mg/dL)
- Subjects with other single organ failure with i. Renal impairment (defined as an increase in creatinine of > 0.3 mg/dL from either an established prior Baseline level or if applicable, upon admission to hospital if prior level is unavailable; for inclusion, the creatinine level must be raised above normal levels), and/or ii. Hepatic encephalopathy grade I or II
- Subjects with two organ failures
-
If a subject received steroids for alcohol-induced acute liver failure, he/she must be unresponsive to steroid therapy. Responsiveness is based on investigator discretion.
-
Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from screening to one month after the last dose of study drug
- Known infection with HIV
- Subjects with cirrhosis who develop decompensation at any time in the postoperative period following partial hepatectomy
- Subjects with evidence of uncontrolled infection defined as persistent bacterial culture positivity despite adequate antibiotic therapy
- Subjects with clinical evidence of disseminated intravascular coagulation
- Subjects with chronic and/or pre-existing kidney disease defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min for 3 months or longer
- Subjects who are hypotensive (defined as mean arterial pressure <70 mmHg) or require the use of inotropic support
- Subjects with evidence of significant and/or uncontrolled bleeding
- Subjects requiring mechanical ventilation
- Subjects with active or history of malignancies other than hepatocellular carcinoma (HCC) within Milan criteria or curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for five or more years
- Subjects previously exposed to IDN-6556
- History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of > 480 milliseconds (msec)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Dosed twice daily IDN-6556 5 mg IDN-6556 Dosed twice daily IDN-6556 25 mg IDN-6556 Dosed twice daily IDN-6556 50 mg IDN-6556 Dosed twice daily
- Primary Outcome Measures
Name Time Method Area Under the Curve (AUC) 28 days Primary endpoints for AUC_0-8, AUC_0 last, AUC_0-inf on Day 1 and Day 4 for the active treatment arms were analyzed.
Tmax & t1/2 Parameters 28 Days Primary endpoints for tmax \& t1/2 on Day 1 and Day 4 for the active treatment arms were analyzed.
Cmax 28 Days Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.
- Secondary Outcome Measures
Name Time Method Levels of CK18/M30 Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 Caspase-cleaved cytokeratin serum levels (CK18/M30)
Levels of CK18/M65 Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 Caspase full-length cytokeratin serum levels CK18/M65
Levels of Caspase 3/7 RLU Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 Concentration of Caspase 3/7 Relative Light Units
Trial Locations
- Locations (26)
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
University College London, Royal Free Hospital
🇬🇧London, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon tyne, United Kingdom
VA San Diego Healthcare System
🇺🇸San Diego, California, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Central Manchester University Hospitals NHS Trust
🇬🇧Manchester, United Kingdom
Ninewells Hospital
🇬🇧Dundee, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Singleton Hospital
🇬🇧Swansea, Wales, United Kingdom
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Sutter Pacific Medical Foundation
🇺🇸San Francisco, California, United States
Univerisity of Louisville Liver Research Center
🇺🇸Louisville, Kentucky, United States
Basildon and Thurrock University Hospital
🇬🇧Basildon, United Kingdom
Queen Alexandra Hospital
🇬🇧Portsmouth, United Kingdom
Scripps Clinic
🇺🇸La Jolla, California, United States
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
University of Washington Harborview Medical Center
🇺🇸Seattle, Washington, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom