Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01937130
Recruitment Status : Terminated (Data needs met)
First Posted : September 9, 2013
Results First Posted : April 11, 2016
Last Update Posted : April 11, 2016
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Acute on Chronic Hepatic Failure Acute Liver Failure Liver Cirrhosis Acute Alcoholic Hepatitis Drug: IDN-6556 Other: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : September 2013
Actual Primary Completion Date : January 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: IDN-6556 5 mg
Dosed twice daily
Drug: IDN-6556
Other Names:
  • emricasan
  • PF-03491390

Experimental: IDN-6556 25 mg
Dosed twice daily
Drug: IDN-6556
Other Names:
  • emricasan
  • PF-03491390

Experimental: IDN-6556 50 mg
Dosed twice daily
Drug: IDN-6556
Other Names:
  • emricasan
  • PF-03491390

Placebo Comparator: Placebo
Dosed twice daily
Other: Placebo

Primary Outcome Measures :
  1. Area Under the Curve (AUC) [ Time Frame: 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.

  2. Cmax [ Time Frame: 28 Days ]
    Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.

  3. Tmax & t1/2 Parameters [ Time Frame: 28 Days ]
    Primary endpoints for tmax & t1/2 on Day 1 and Day 4 for the active treatment arms were analyzed.

Secondary Outcome Measures :
  1. Levels of CK18/M30 [ Time Frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 ]
    Caspase-cleaved cytokeratin serum levels (CK18/M30)

  2. Levels of CK18/M65 [ Time Frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 ]
    Caspase full-length cytokeratin serum levels CK18/M65

  3. Levels of Caspase 3/7 RLU [ Time Frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28 ]
    Concentration of Caspase 3/7 Relative Light Units

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01937130

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Scripps Clinic
La Jolla, California, United States, 92037
VA San Diego Healthcare System
San Diego, California, United States, 92161
Sutter Pacific Medical Foundation
San Francisco, California, United States, 94115
United States, District of Columbia
Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
Univerisity of Louisville Liver Research Center
Louisville, Kentucky, United States, 40202
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
University of Washington Harborview Medical Center
Seattle, Washington, United States, 98104
United Kingdom
Singleton Hospital
Swansea, Wales, United Kingdom, SA2 8QA
Basildon and Thurrock University Hospital
Basildon, United Kingdom, SS16 5NL
Blackpool Victoria Hospital
Blackpool, United Kingdom, FY3 8NR
Bristol Royal Infirmary
Bristol, United Kingdom, BS2 8HW
Ninewells Hospital
Dundee, United Kingdom, DD1 9SY
Glasgow Royal Infirmary
Glasgow, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP
University College London, Royal Free Hospital
London, United Kingdom, NW3 2PF
Royal London Hospital
London, United Kingdom
Central Manchester University Hospitals NHS Trust
Manchester, United Kingdom, M13 9WL
Freeman Hospital
Newcastle upon tyne, United Kingdom, NE7 7DN
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom, NG7 2UH
Derriford Hospital
Plymouth, United Kingdom
Queen Alexandra Hospital
Portsmouth, United Kingdom, PO6 3LY
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Principal Investigator: Stephen Ryder, Dr. Nottingham University Hospital NHS Trust

Responsible Party: Conatus Pharmaceuticals Inc. Identifier: NCT01937130     History of Changes
Other Study ID Numbers: IDN-6556-02
First Posted: September 9, 2013    Key Record Dates
Results First Posted: April 11, 2016
Last Update Posted: April 11, 2016
Last Verified: March 2016

Keywords provided by Conatus Pharmaceuticals Inc.:
Liver Failure
Alcoholic Hepatitis

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Failure
Hepatitis, Alcoholic
Acute-On-Chronic Liver Failure
Liver Failure, Acute
End Stage Liver Disease
Liver Diseases
Digestive System Diseases
Pathologic Processes
Hepatic Insufficiency
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders