Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Conatus Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01937130
First received: September 4, 2013
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Acute on Chronic Hepatic Failure
Acute Liver Failure
Liver Cirrhosis
Acute Alcoholic Hepatitis
Drug: IDN-6556
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Conatus Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    The pharmacokinetic variables for IDN-6556 will be tabulated and summarized.


Secondary Outcome Measures:
  • Pharmacodynamics [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Serum and urine biomarkers of mechanistic activity will be tabulated and summarized.

  • Adverse events [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Reported AEs will be tabulated. Changes in hospital status (i.e., change from general ward to intensive care ward) will be assessed.

  • Clinical outcomes [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Listings of clinical events (transplantation, progression to next organ failure and death) will be listed and summarized by treatment group.


Estimated Enrollment: 60
Study Start Date: September 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01937130

Contacts
Contact: Gary Burgess, MD +44 (0)7879602104 gburgess@conatuspharma.com
Contact: MiRa Huyghe 858-457-7227 mhuyghe@conatuspharma.com

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

No publications provided

Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01937130     History of Changes
Other Study ID Numbers: IDN-6556-02
Study First Received: September 4, 2013
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Cirrhosis
Fibrosis
Liver Failure
Liver Failure, Acute
End Stage Liver Disease
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Pathologic Processes
Hepatic Insufficiency

ClinicalTrials.gov processed this record on July 22, 2014