Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

Liver Cirrhosis Clinical Trial

Official title:

A Placebo-Controlled, Multicenter, Double-Blind, Randomized, Pharmacokinetic and Pharmacodynamic Trial of IDN-6556 in Subjects With Acute-on-Chronic Liver Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01937130
• Other study ID #: IDN-6556-02
• Status: Terminated
• Phase: Phase 2
• First received: September 4, 2013
• Last updated: October 29, 2015
• Start date: September 2013
• Est. completion date: February 2015

Study information

• Verified date: October 2015
• Source: Conatus Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: February 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Alcoholic Hepatitis
• Acute Liver Failure
• Acute on Chronic Hepatic Failure
• Hepatitis, Alcoholic
• Liver Cirrhosis
• Liver Failure
• Liver Failure, Acute

Intervention

Drug:
• IDN-6556

Other:
• Placebo

Locations

Country	Name	City	State
United Kingdom	Basilson and Thurrock University Hospital	Basildon
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Royal London Hospital	London
United Kingdom	University College London, Royal Free Hospital	London
United Kingdom	Central Manchester University Hospitals NHS Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle upon tyne
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Queen Alexandra Hospital	Portsmouth
United Kingdom	Singleton Hospital	Swansea	Wales
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Clinic	La Jolla	California
United States	Univerisity of Louisville Liver Research Center	Louisville	Kentucky
United States	University of Utah	Salt Lake City	Utah
United States	VA San Diego Healthcare System	San Diego	California
United States	Sutter Pacific Medical Foundation	San Francisco	California
United States	University of Washington Harborview Medical Center	Seattle	Washington
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Conatus Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics	The pharmacokinetic variables for IDN-6556 will be tabulated and summarized.	28 days	Yes
Secondary	Pharmacodynamics	Serum and urine biomarkers of mechanistic activity will be tabulated and summarized.	28 days	No
Secondary	Adverse events	Reported AEs will be tabulated. Changes in hospital status (i.e., change from general ward to intensive care ward) will be assessed.	28 days	Yes
Secondary	Clinical outcomes	Listings of clinical events (transplantation, progression to next organ failure and death) will be listed and summarized by treatment group.	28 days	Yes