Companion Protocol for the ¹³C-Methacetin Breath Test Using the BreathID® MCS System for Conatus Phase 2 Study of Emricasan, an Oral Caspase Inhibitor, Under Protocol IDN-6556-14 (NCT02960204)

CON-EX-0616

To validate the ability of the Methacetin Breath Test (MBT) to detect clinically significant portal hypertension (CSPH)/severe portal hypertension (SPH) defined as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg and HVPG ≥ 12 mmHg respectively, in patients with non-alcoholic steatohepatitis (NASH) during the course of treatment with Conatus's investigational product emricasan/placebo.

2016-08-28

2019-04-08

2019-05-13

Completed

343

Inclusion Criteria: 1. 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. 2. Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.) 3. Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event. 4. Severe portal hypertension defined as HVPG ≥12 mmHg 5. 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 6. 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: 1. Evidence of severe decompensation 2. Severe hepatic impairment defined as a Child-Pugh score ≥10 3. ALT \>3 times upper limit of normal (ULN) or AST \>5 times ULN during screening 4. Estimated creatinine clearance \<30 mL/min 5. Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure 6. Known portal vein thrombosis 7. Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy, other definitive treatment (e.g. sphincterotomy), or medical management (e.g. ursodeoxycholic acid) 8. Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters 9. Alpha-fetoprotein \>50 ng/mL 10. History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of \>500 msec 11. History of or active malignancies, other than those successfully treated with curative intent and believed to be cured 12. Prior liver transplant 13. Change in diabetes medications or vitamin E within 3 months of screening 14. Uncontrolled diabetes mellitus (HbA1c \>9%) within 3 months of screening 15. Significant systemic or major illness other than liver disease 16. HIV infection 17. Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening 18. If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding 19. Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1

{'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'The population performing the MBT at weeks 24 and 48 will have approximately an equal number of subjects from each of the 4 parallel treatment arms (5 mg, 25 mg, 50 mg or placebo).', 'primaryPurpose': 'DIAGNOSTIC', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'The collaborator is responsible for the masking process.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 343, 'type': 'ACTUAL'}}

2022-12-20