Efficacy and Safety Study of Ammonul® in Patients With Grade 3 or 4 Hepatic Encephalopathy

Inclusion Criteria:

* Male or female between the ages of 18 and 75 years
* Signed written informed consent by subject's representative
* Current diagnosis of chronic liver disease with cirrhosis
* West Haven score of Grade 3 or 4 Hepatic Encephalopathy
* Weight between 45 and 150 kg
* Elevated venous ammonia concentration, defined as a value above the normal range at the local laboratory
* Estimated creatinine clearance of \> 30 mL/min/1.73m², calculated using the Cockcroft-Gault formula, or serum creatinine \< 2.5 mg/dL \[Cockcroft-Gault formula: creatinine clearance = (140 - age) x weight in kg divided by (72 x serum creatinine in mg/dL); multiply result by 0.85 for females\]
* Adequate urinary output of ≥ 30 mL/hour for the last 2 hours if estimated creatinine clearance is \< 50 mL/min/1.73 m²
* Negative pregnancy test or documented sterilization procedure (tubal ligation or hysterectomy) or 5 years post-menopausal

Exclusion Criteria:

* Major gastrointestinal bleeding (hematemesis, melena, or hematochezia) requiring blood transfusion within the last 24 hours
* Uncontrolled sepsis, as defined by hemodynamic instability requiring vasopressor agents (renal-dosed dopamine allowed)
* Current diagnosis of acute hepatic failure
* Alcohol ingestion during last 24 hours
* Post liver transplant
* Serum sodium \< 120 mEq/L
* Serum potassium ≤ 3.5 mEq/L
* Use of probenecid, valproate, penicillin or its derivatives, or corticosteroids (oral or IV) within the last 24 hours
* Use of any sedatives, benzodiazepines, or any neuro- or psycho-active drugs in the last 6 hours and a positive urinary drug screen
* Subjects who received any mind-altering agents (such as barbiturates, propofol, opioids, or benzodiazepines) to assist with intubation are not eligible while the effects of the drug are still apparent
* Congestive heart failure (New York Heart Association Class III or IV)
* Seizures, dementia, or any neurologic or psychiatric condition within the last 72 hours that may interfere with the assessment of the mental state
* Current diagnosis of major aspiration pneumonia or pulmonary edema accompanied by an oxygen saturation of ≤ 90% while breathing supplemental oxygen
* Laboratory test abnormalities determined to be clinically significant by the investigator
* Enrollment in another experimental (interventional) protocol within the last 30 days or 5 half-lives of the experimental drug, whichever s longer
* Any medical condition, which in the opinion of the investigator would constitute a contraindication to enrollment in the study