MNK6106 for Liver Disease (Hepatic Cirrhosis) That in the Past Has Affected the Brain (Hepatic Encephalopathy)

• ClinicalTrials.gov Identifier: NCT03712280
• Recruitment Status: Completed
• First Posted: October 19, 2018
• Results First Posted: July 20, 2021
• Last Update Posted: July 20, 2021
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

Study Description

Brief Summary:

The main reason for this study is to see how the study drug interacts with the body.

It will compare different doses of the study drug with a drug already in use.

Participants will be adults with liver disease that has affected the brain in the past.

Condition or disease	Intervention/treatment	Phase
Hepatic Cirrhosis; Hepatic Encephalopathy (HE)	Drug: MNK6106; Drug: Rifaximin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase 2a Comparator Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK6106 (L-Ornithine Phenylacetate) Versus Rifaximin in Subjects With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy
• Actual Study Start Date: December 1, 2018
• Actual Primary Completion Date: July 14, 2020
• Actual Study Completion Date: July 14, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A: MNK6106 2 grams (tid); Participants receive 2 tablets of MNK6106 three times daily (tid) for 5 days	Drug: MNK6106; 1 gram tablet of MNK6106 for oral administration; Other Names: Study Drug; L-Ornithine Phenylacetate
Experimental: Group B: MNK6106 4 grams (bid); Participants receive 4 tablets of MNK6106 twice daily (bid) for 5 days	Drug: MNK6106; 1 gram tablet of MNK6106 for oral administration; Other Names: Study Drug; L-Ornithine Phenylacetate
Experimental: Group C: MNK6106 4 grams (tid); Participants receive 4 tablets of MNK6106 tid for 5 days	Drug: MNK6106; 1 gram tablet of MNK6106 for oral administration; Other Names: Study Drug; L-Ornithine Phenylacetate
Active Comparator: Group D: Rifaximin 550 mg (bid); Participants receive 1 tablet of rifaximin bid for 5 days	Drug: Rifaximin; 550 mg tablet of rifaximin for oral administration; Other Name: Xifaxan

Outcome Measures

Primary Outcome Measures :

1. Ammonia Plasma Levels at Baseline and Day 5 [ Time Frame: Baseline, Day 5 ]

   This test measures the level of ammonia in your blood. Ammonia, also known as NH3, is a waste product made by your body during the digestion of protein. Normally, ammonia is processed in the liver, where it is changed into another waste product called urea. Urea is passed from the body in urine.

   If your body cannot process or eliminate ammonia, a lab test of a blood sample shows it has built up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including hepatic encephalopathy.

Secondary Outcome Measures :

1. Number of Participants With Adverse Events by the End of the Trial [ Time Frame: within 15 days ]
   End of trial is defined as 7 (+/-3) days after last study treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

A potential participant may only be included if (at screening), he/she:

1. Understands the study and has signed informed consent
2. Is an adult, not pregnant or lactating
3. Has cirrhosis of the liver
4. Has had 1 instance of HE within 12 months
5. Has hyperammonaemia defined as ≥37 μmol/L at screening

Key Exclusion Criteria:

A potential participant will be excluded if (at screening), he/she:

1. Has contraindicated allergies
2. Expects liver transplant within 1 month
3. Has had a liver shunt within the last 3 months
4. Has inadequate kidney, gastrointestinal, or cardiac function

5. Has cancer, infection, lab abnormalities, or any other condition that, per protocol or in the opinion of the investigator might compromise:

   1. the safety and well-being of the participant or potential offspring
   2. the safety of study staff
   3. the analysis of results

Contacts and Locations

Locations

United States, California

Southern California Research Center

Coronado, California, United States, 92118

Inland Empire Clinical Trials

Rialto, California, United States, 92377

United States, Florida

Global Clinical Professionals

Saint Petersburg, Florida, United States, 33702

United States, Texas

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, United States, 78215

Puerto Rico

Fundacion de Investigacion (Research Foundation)

San Juan, Puerto Rico, 00927

Sponsors and Collaborators

Mallinckrodt

Investigators

• Study Director: Clinical Team Leader; Mallinckrodt

  Study Documents (Full-Text)

Documents provided by Mallinckrodt:

Study Protocol and Statistical Analysis Plan  [PDF] April 21, 2020

More Information

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT03712280
• Other Study ID Numbers: MNK61062107
• First Posted: October 19, 2018
• Results First Posted: July 20, 2021
• Last Update Posted: July 20, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT03712280) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Liver Cirrhosis; Hepatic Encephalopathy; Brain Diseases; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Failure; Hepatic Insufficiency; Brain Diseases, Metabolic; Metabolic Diseases; Rifaximin; Phenylacetic acid; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents