Companion Protocol for Methacetin Breath Test (MBT) in Conatus Protocol IDN-6556-14

Inclusion Criteria

• Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
• Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
• Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event.
• Severe portal hypertension defined as HVPG ≥12 mmHg
• Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1
• Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug

Exclusion Criteria

• Evidence of severe decompensation
• Severe hepatic impairment defined as a Child-Pugh score ≥10
• ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
• Estimated creatinine clearance 50 ng/mL
• History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec
• History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
• Prior liver transplant
• Change in diabetes medications or vitamin E within 3 months of screening
• Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
• Significant systemic or major illness other than liver disease
• HIV infection
• Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
• If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
• Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1