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

NCT ID: NCT03439189

Last Updated: 2022-12-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

343 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-28

Study Completion Date

2019-05-13

Brief Summary

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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.

Detailed Description

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This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-14 (NCT02960204).The IDN-6556-14 study is a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial in subjects with non-alcoholic steatohepatitis (NASH) cirrhosis and severe portal hypertension.

As one of the Conatus' study exploratory objectives, this companion protocol is designed to assess whether emricasan compared to placebo improves liver metabolic function at Weeks 24 and 48 as assessed by the methacetin breath test (at select sites), if relevant.

Conditions

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NASH - Nonalcoholic Steatohepatitis Cirrhosis Portal Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
The collaborator is responsible for the masking process.

Study Groups

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Emricasan 5mg

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.

Group Type EXPERIMENTAL

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Emricasan

Intervention Type DRUG

Investigational drug for NASH treatment in Main Conatus protocol

Emricasan 25mg

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.

Group Type EXPERIMENTAL

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Emricasan

Intervention Type DRUG

Investigational drug for NASH treatment in Main Conatus protocol

Emricasan 50mg

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.

Group Type EXPERIMENTAL

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Emricasan

Intervention Type DRUG

Investigational drug for NASH treatment in Main Conatus protocol

Placebo

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.

Group Type PLACEBO_COMPARATOR

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Placebo oral capsule

Intervention Type DRUG

Placebo versus emricasan in Conatus NASH treatment trial

Interventions

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Methacetin Breath Test

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Intervention Type COMBINATION_PRODUCT

Emricasan

Investigational drug for NASH treatment in Main Conatus protocol

Intervention Type DRUG

Placebo oral capsule

Placebo versus emricasan in Conatus NASH treatment trial

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Conatus Pharmaceuticals Inc.

INDUSTRY

Sponsor Role collaborator

Meridian Bioscience, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hopital Beaujon

Clichy, , France

Site Status

Countries

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Spain United States France

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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CON-EX-0616

Identifier Type: -

Identifier Source: org_study_id