Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

March 28, 2016 updated by: Conatus Pharmaceuticals Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
28 days
Cmax
Time Frame: 28 Days
Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.
28 Days
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.
28 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
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
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
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
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Conatus Pharmaceuticals Inc.

Investigators

  • Principal Investigator: Stephen Ryder, Dr., Nottingham University Hospital NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

September 4, 2013

First Submitted That Met QC Criteria

September 4, 2013

First Posted (Estimate)

September 9, 2013

Study Record Updates

Last Update Posted (Estimate)

April 11, 2016

Last Update Submitted That Met QC Criteria

March 28, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDN-6556-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Liver Cirrhosis

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Brazil

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe