Clinical trial NCT01937130: Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF
Official title: A Placebo-Controlled, Multicenter, Double-Blind, Randomized, Pharmacokinetic and Pharmacodynamic Trial of IDN-6556 in Subjects With Acute-on-Chronic Liver Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute on Chronic Hepatic Failure
Acute Liver Failure
Liver Cirrhosis
Acute Alcoholic Hepatitis
Keywords: Liver Failure
Cirrhosis
Alcoholic Hepatitis
Lead sponsor: Conatus Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2013-09-09
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Subjects with renal failure (defined as creatinine ≥ 2.0 to ≤ 3.4 mg/dL)
  2. 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
  3. 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Area Under the Curve (AUC)
timeFrame: 28 days
measure: Cmax
timeFrame: 28 Days
measure: Tmax & t1/2 Parameters
timeFrame: 28 Days
Secondary outcomes:
measure: Levels of CK18/M30
timeFrame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
measure: Levels of CK18/M65
timeFrame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
measure: Levels of Caspase 3/7 RLU
timeFrame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: San Francisco
country: United States
facility: Sutter Pacific Medical Foundation
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Univerisity of Louisville Liver Research Center
state: Kentucky
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington Harborview Medical Center
state: Washington
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Basildon
country: United Kingdom
facility: Basildon and Thurrock University Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: University College London, Royal Free Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Trust
city: Newcastle upon tyne
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
Study officials:
affiliation: Nottingham University Hospital NHS Trust
name: Stephen Ryder, Dr.
role: PRINCIPAL_INVESTIGATOR
References: