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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Cirrhosis, Hepatic Encephalopathy (HE)

Intervention / Treatment
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* Drug: MNK6106
* Drug: Rifaximin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A potential participant may only be included if (at screening), he/she: Understands the study and has signed informed consent Is an adult, not pregnant or lactating Has cirrhosis of the liver Has had 1 instance of HE within 12 months Has hyperammonaemia defined as ≥37 μmol/L at screening Key Exclusion Criteria: A potential participant will be excluded if (at screening), he/she: Has contraindicated allergies Expects liver transplant within 1 month Has had a liver shunt within the last 3 months Has inadequate kidney, gastrointestinal, or cardiac function Has cancer, infection, lab abnormalities, or any other condition that, per protocol or in the opinion of the investigator might compromise: the safety and well-being of the participant or potential offspring the safety of study staff the analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ammonia Plasma Levels at Baseline and 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. | Baseline, Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events by the End of the Trial | End of trial is defined as 7 (+/-3) days after last study treatment | within 15 days |