OCR002-SP103 - Oral Immediate Release Study

Exclusion Criteria

• •Subjects meeting any of the following criteria will not be eligible for enrollment:
• •1. Not expected to survive for 2 months;
• •2. Presence of Type 1 hepatorenal syndrome;
• •3. Presence of hyponatremia (serum sodium \<125 mmol/L);
• •4. Presence of renal failure with serum creatinine \>3 mg/dL or need for hemodialysis, peritoneal dialysis, or continuous venovenous hemofiltration at Screening;
• •5. New York Heart Association Class 3 or 4 congestive heart failure or overt clinical signs of congestive heart failure;
• •6. Requirement for mechanical ventilation (continuous positive airway pressure is allowed);
• •7. Prior transplant recipient (solid organ, bone marrow, or stem cell);
• •8. Any prior stroke with cognitive sequelae;
• •9. Presence of acute alcoholic hepatitis;
• •10. Positive test for human immunodeficiency virus or hepatitis B surface antigen;
• •11. Presence of overt hepatic encephalopathy, other irreversible brain damage, aspiration pneumonia, or severe psychiatric disorder;
• •12. Known or suspected gastrointestinal bleeding within 7 days before Screening;
• •13. Hemodynamic instability, defined as mean arterial blood pressure \<60 mmHg and/or evidence of poor organ perfusion;
• •14. Current use of more than 1 vasopressor to support blood pressure;
• •15. Current use of drugs that could potentially interfere with renal excretion of PAGN, such as probenecid, estrone sulfate, ibuprofen, cimetidine, or diclofenac. Use of L-ornithine L-aspartate is prohibited;
• •16. Current use of drugs whose renal excretion may be affected by OCR-002, such as quinidine, metformin, or cimetidine;
• •17. Current use of molecular adsorbent recirculation system;
• •18. Current use of AMMONUL (sodium benzoate with sodium phenylacetate), BUPHENYL (sodium phenylbutyrate), RAVICTI, or other medications that contain sodium benzoate or sodium phenylbutyrate.
• •19. Current use of rifaximin or oral neomycin;
• •20. Corrected QT interval (Fridericia's formula) \>480 msec at Day -1;
• •21. History or allergic reactions to ornithine, PAA, or their analogs;
• •22. Currently hospitalized for any reason or clinically significant surgery within 4 weeks before the first dose of the study drug;
• •23. Presence of transjugular intrahepatic portosystemic shunt;
• •24. Blood loss or blood donation of \>500 mL within 30 days or plasma donation \>500 mL within 14 days before administration of the first dose of study drug;
• •25. Currently lactating;
• •26. Positive screening result for drugs of abuse;
• •27. Ingestion of grapefruit or grapefruit juice within 48 hours before study dose administration; or use of repaglinide throughout the study;
• •28. Receipt of an investigational product or device, or participation in a drug research study within a period of 30 days (or 5 half-lives of the drug, whichever is longer) before the first dose of study drug;
• •29. Prior diagnosis of cancer and receiving active therapy, or hepatic cancer or cancer with known brain metastasis;
• •30. Any condition or set of circumstances which, in the judgment of the Investigator or Sponsor, could interfere with their ability to comply with the dosing schedule and completion of the study evaluations.
• •31. Prior surgical shunt recipient (Part 2)
• •32. Subject has a body weight \<45 kg (Part 2).
• •33. Current use of oral vancomycin or oral or parenteral antibiotic that could potentially alter gut flora (Part 2)