A Single Oral Dose Study of DUR-928 in Nonalcoholic Steatohepatitis (NASH) Patients and Healthy Volunteers

Exclusion Criteria34

• For subjects with cirrhosis there must be a prior histological evidence of cirrhosis or clinical and/or radiological evidence of cirrhosis in conjunction with a FibroScan greater than or equal to 12.5 kPa and Child Pugh A 5-6.
• For non cirrhosis subjects there must be prior histological evidence for the absence of cirrhosis within the past 12 months or the absence of clinical and/or radiological evidence for cirrhosis in conjunction with a FibroScan less than 9.5 kPa.
• For cirrhotic/non-cirrhotic indeterminate subjects will include subjects who have:
• (a) Fibroscan greater than or equal to 12.5 but no radiological evidence of cirrhosis
• (b) Fibroscan less than 12.5 but greater than or equal 9.5
• (c) Clinical / radiological features of cirrhosis but Fibroscan less than 9.5
• Healthy Volunteers (in addition to “All Participants”)
• Subjects must have normal hepatic function.
• Demographically comparable to NASH subjects as follows:
• ^ Mean BMI (kg/m2) within +/- 25%
• ^ Mean age within +/- 10 years
• ^ Similar gender ratio
• All participants:
• Disease or surgery of the gastrointestinal tract that may interfere with drug absorption or may otherwise influence the pharmacokinetics of the investigational medicinal product
• Participation in an investigational drug study within 30 days prior to dosing.
• History of drug or alcohol abuse.
• Disease or surgery of the gastrointestinal tract that may interfere with drug absorption or may otherwise influence the pharmacokinetics of the investigational medicinal product (e.g., inflammatory bowel disease, restrictions of the small or large intestine, etc.)
• History of febrile illness within 5 days prior to dosing.
• Positive tests for HIV, hepatitis B, drugs of abuse or alcohol breath-test.
• Clinically significant abnormalities
• Women of child-bearing potential, pregnant or nursing (lactating) women
• NASH Subjects (in addition to “All Participants”)
• Subject has evidence of other forms of chronic liver disease
• Hepatic Cirrhosis with a Child-Pugh classification of B or C (score > 6)
• Alcohol use greater than or equal to 30 g/day
• Type I diabetes
• History of bariatric surgery
• Concurrent Anti-NASH therapy(s) with washout less than or equal to 30 days
• Viral hepatitis (i.e., serologies for Hepatitis B and C should be negative) However, subjects who are Hepatitis C Virus (HCV)-antibody positive but hepatitis C virus-ribonucleic acid (HCV-RNA) negative who have been successfully treated with antiviral agents and have a sustained virological response (SVR) following HCV therapy or documentation of HCV-RNA negative for a minimum of 6 months prior to inclusion and who meet all other eligibility criteria may be considered for enrollment.
• Healthy Volunteers (in addition to “All Participants”)
• 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 the time of dosing)
• Presence of impaired renal function as indicated by abnormal creatinine (creatinine clearance < 80 ml/min) values and/or serum creatinine greater than or equal to 1.8 mg/dL
• History of regular alcohol consumption exceeding 28 drinks/week within 6 months of screening
• Positive tests for hepatitis C.