Pharmacodynamics, Safety and Pharmacokinetics of the Oral Administration MNK6106 (L-ornithine Phenylacetate) vs Rifaximin in Participants With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy

Key Inclusion Criteria:

Must have the ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures.

1. Adult male and non-pregnant, non-lactating females

2. Known or evident liver cirrhosis. Diagnosis of liver cirrhosis may be based on
clinical, radiological, and or histological criteria, including 1 or more of the
following:

1. Liver biopsy (documented by histology);

2. Clinical evidence of cirrhosis, defined as aspartate aminotransferase (AST) >
alanine aminotransferase (ALT) (i.e., AST > ALT), platelet count < 150,000, and
nodular liver surface on computed tomography (CT) scan or magnetic resonance
imaging (MRI);

3. Clinical evidence of significant portal hypertension, based on current or history
of gastroesophageal varices on endoscopy, evidence of portosystemic collaterals
(on contrast CT or MRI with contrast), and/or presence of ascites;

4. Transient elastography consistent with cirrhosis, i.e., result of > 13.0
kilopascal (kPa).

3. History of at least 2 or more documented episodes of HE within the last 12 months,
with 1 episode within the last 6 months.

4. Hyperammonemia at Screening, defined as elevated venous AMM level > 1.3 × upper limit
of normal (ULN) (and not < 50 μmol/L) at local laboratory.

Key Exclusion Criteria: A subject is ineligible for study participation if, at the
Screening Visit, the subject:

1. Has a history of sensitivity or allergy to MNK6106, Ornithine (ORN) Phenylacetate
(PAA), L-ornithine L-aspartate (LOLA), phenylbutyrate or rifaximin.

2. Expectation of liver transplantation within 1 month after Screening Visit.

3. Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt
(TIPS) within 3 months before Screening Visit.

4. Gastrointestinal hemorrhage within 3 months of Screening Visit.

5. Severe renal impairment (glomular filtration rate ≤ 30 mL/min).

6. Intercurrent infection or active spontaneous bacterial peritonitis.

7. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus or hepatitis D
virus

8. Has any solid tumor malignancy currently diagnosed or undergoing therapy, or has
received therapy for any solid tumor malignancy in the 5 years prior to the Screening
Visit; with the exception of treated and cured basal cell carcinoma, treated and cured
squamous cell carcinoma of the skin, and treated and cured carcinoma in situ of the
cervix.

9. Positive screening result for drugs of abuse.

10. Have a QT interval corrected using Fridericia's Formula (QTcF) ≥ 500 ms at Screening.

11. Has any of the following laboratory abnormalities at the Screening Visit:

- Hemoglobin ≤ 8.0 g/dL.

- Platelets ≤ 50,000 cells/μL.

- Absolute neutrophil count ≤ 1000 cells/μL.

12. Has any other clinically significant disease, disorder or laboratory abnormality

13. Use of another investigational agent within 90 days of screening, unless allowed by
the sponsor.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.