PK and PD Study of IDN-6556 in Subjects With Hepatic Impairment and Matched Healthy Volunteers
Condition: Hepatic Impairment; Liver Diseases; Digestive System Diseases
MeSH terms: Liver Diseases; Digestive System Diseases; Gastrointestinal Diseases
Intervention: IDN-6556
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hepatic Impairment; Pharmacokinetics; Pharmacodynamics

Summary:

      This is an open-label, parallel-group study to compare the pharmacokinetics and
      pharmacodynamics of IDN-6556 following a single 50 mg oral dose of IDN-6556 in subjects with
      mild, moderate, and severe hepatic impairment (defined as Child-Pugh A, B, and C,
      respectively) and matched healthy volunteers with normal hepatic function.
    

Eligibility criteria:

        Inclusion Criteria:

        All Subjects:

          -  Male or female subjects 18 years of age or older, able to provide written informed
             consent, understand and comply with all scheduled visits, and other requirements of
             the study

          -  Body mass index (BMI) 18.0 - 40.0 kg/m2 and body weight >45 kg

          -  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

        Matched Healthy Volunteers:

          -  Medically healthy as determined by the Investigator

          -  Supine blood pressure ≤145/90 mmHg

          -  No significant uncontrolled systemic or major illness that, in the opinion of the
             Investigator, would preclude the subject from participating in and completing the
             study

          -  Demographically comparable to subjects with hepatic impairment as follows:

               1. Mean body weight within ±15 kg

               2. Mean age within ±10 years

               3. Similar gender ratio

        Subjects with Hepatic Impairment:

          -  Evidence of hepatic disease

               1. Score ≥ 2 on one of the Child-Pugh parameters, or

               2. Histological or imaging diagnosis of cirrhosis, or

               3. Presence of esophageal varices, or

               4. Abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
                  alkaline phosphatase (ALP) levels

          -  Meet one of the following criteria for Child-Pugh classification for hepatic
             impairment during Screening

               1. Mild hepatic impairment: Class A (Child-Pugh Scores 5-6 points)

               2. Moderate hepatic impairment: Class B (Child-Pugh Scores 7-9 points)

               3. Severe hepatic impairment: Class C (Child Pugh Scores 10-15 points)

          -  Supine blood pressure ≤160/100 mmHg

        Exclusion Criteria:

        All Subjects:

          -  Known infection with human immunodeficiency virus (HIV) upon serological testing

          -  Evidence of clinically significant uncontrolled hematological, endocrine, pulmonary,
             gastrointestinal, cardiovascular, renal, psychiatric, neurologic, or allergic disease
             (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies
             at time of dosing)

          -  Disorders or surgery of the gastrointestinal tract which may interfere with drug
             absorption or may otherwise influence the pharmacokinetics of the investigational
             medicinal product (e.g., inflammatory bowel disease, resections of the small or large
             intestine, etc.)

          -  History of febrile illness within 5 days prior to dosing Note: Subjects can be
             rescreened once afebrile and more than 5 days have elapsed since the febrile illness.

          -  Known ongoing drug abuse within one month prior to dosing, or evidence of such abuse
             as indicated by the laboratory assays conducted during Screening and/or at Day -1

          -  Subjects with active or history of malignancies other than curatively treated skin
             cancer (basal cell or squamous cell carcinomas)

          -  Dosing in another clinical trial within 30 days prior to the study drug administration

          -  If female: known pregnancy, positive urine or serum pregnancy test, or
             lactating/breastfeeding

        Matched Healthy Volunteers:

          -  Evidence of clinically significant liver disease or liver damage (e.g., hepatitis B or
             C, autoimmune hepatitis, primary biliary cirrhosis, non-alcoholic fatty liver disease,
             elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that is
             considered clinically significant by the Investigator, etc.)

          -  Screening creatinine clearance <80 mL/min using the Cockcroft-Gault equation

          -  History or presence of clinically concerning cardiac arrhythmias, or prolongation of
             Screening (pre-treatment) QT or QTc interval of >450 milliseconds (msec)

          -  History of regular alcohol consumption exceeding 28 drinks/week (1 drink = 150 mL of
             wine or 360 mL of beer or 45 mL of spirits) within 6 months of Screening

        Subjects with Hepatic Impairment:

          -  Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly
             varying or worsening of clinical and/or laboratory signs of hepatic impairment during
             Screening period and up to Day -1 (e.g., advanced ascites, infection of ascites,
             fever, active gastrointestinal bleeding)

          -  History of liver transplant, or have a transjugular intrahepatic portosystemic shunt,
             and/or have undergone portacaval shunting

          -  History or presence of clinically concerning cardiac arrhythmias, or prolongation of
             Screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec)

          -  Screening creatinine clearance <50 mL/min using the Cockcroft-Gault equation