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

• Status: Terminated
• Trial end date: 2008-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary purpose of this study is to evaluate the safety and effectiveness of Ammonul® in subjects who become hospitalized with Grade 3 or 4 hepatic encephalopathy (HE).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Treatments: Phenylacetic acid; Sodium Benzoate

Criteria

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