Companion Protocol for Methacetin Breath Test (MBT) in Conatus Protocol IDN-6556-17

NCT ID: NCT03462576

Last Updated: 2022-12-20

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

199 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-28

Study Completion Date

2019-07-15

Brief Summary

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This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-17.The IDN-6556-17 study is a Phase 2, multicenter, double-blind, placebo-controlled trial of Emricasan in subjects with decompensated non-alcoholic steatohepatitis (NASH) cirrhosis.

Detailed Description

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The protocol is intended to validate the ability of the MBT to predict deterioration by 48 weeks for all subjects, and at later time points for those followed longer, for subjects with decompensated NASH cirrhosis in the placebo treatment arm of Conatus' study IDN-6556-17.

As one of the Conatus' study secondary objectives, this companion protocol is designed to assess improvement in liver metabolic function as measured by Methacetin Breath Test (MBT) \[ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) \].

Conditions

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Decompensated Cirrhosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20.

For each subject, the study will consist of:

* Screening period of up to 4 weeks
* Randomized, double-blind treatment period of at least 48 weeks
* A follow-up visit 2 weeks after completion of study drug treatment The duration of each subject's participation will be at least 54 weeks for those completing the entire study.
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 25mg

The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48.

Group Type EXPERIMENTAL

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon 12 to carbon13 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 5mg

The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48.

Group Type EXPERIMENTAL

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon 12 to carbon13 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

The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48.

Group Type PLACEBO_COMPARATOR

Methacetin Breath Test

Intervention Type COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon 12 to carbon13 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 carbon13 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. At least one of the following: a) history of variceal hemorrhage (more than 3 months prior to day 1) documented on endoscopy and requiring blood transfusion, b) history of at least moderate ascites (on physical exam or imaging) currently treated with diuretics.
4. MELD score ≥12 and ≤20 during screening
5. Albumin ≥2.5 g/dL during screening
6. Serum creatinine ≤1.5 mg/dL during screening

Exclusion Criteria

1. Evidence of severe decompensation
2. Non-cirrhotic portal hypertension
3. Child-Pugh score ≥10
4. Current use of anticoagulants that affect prothrombin time or international normalized ratio
5. ALT \>3 times upper limit of normal (ULN) or AST \>5 times ULN during screening
6. Initiation or discontinuation of non-selective beta blockers within 1 month of screening
7. Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
8. Alpha-fetoprotein \>50 ng/mL in the last year
9. History of hepatocellular carcinoma (HCC) or evidence of HCC
10. History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
11. Prior liver transplant
12. Uncontrolled diabetes mellitus (HbA1c \>9%)
13. Change in diabetes medications or vitamin E within 3 months of screening
14. Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
15. Symptoms of biliary colic unless resolved following cholecystectomy
16. History of significant alcohol consumption within the past 5 years
17. Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
18. Prolongation of screening (pre-treatment) QTcF interval of \>500 msecs, or history or presence of clinically concerning cardiac arrhythmias
19. Significant systemic or major illness other than liver disease
20. Human immunodeficiency virus infection
21. Use of alcohol, controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement
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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Florida Digestive Health Specialists Research Institute

Lakewood Rch, Florida, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CON-EX-0217

Identifier Type: -

Identifier Source: org_study_id