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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Two Doses of AMMONUL® (Sodium Phenylacetate and Sodium Benzoate) Injection 10% / 10% in Subjects With G

Brief 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).

Detailed Summary:

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome seen in patients with liver disease. The pathogenesis of HE is incompletely understood, but several pieces of evidence identify ammonia as a key factor in the development of HE. The liver normally detoxifies ammonia produced in the gastrointestinal tract. However, in patients with cirrhosis, portosystemic shunting allows ammonia to bypass the liver and reach the systemic circulation and the brain. The accumulation of ammonia in the brain, through mechanisms not yet fully defined, lead to changes of consciousness, intellectual function, and behavior.

Ammonul is currently approved as adjuvant therapy for the management of hyperammonemia and associated encephalopathy in patients with deficiencies in the enzymes of the urea cycle. Ammonul removes nitrogenous ammonia in these patients through pathways alternative to the urea cycle. It is anticipated that in patients with HE, Ammonul may lead to the scavenging of ammonia through these alternative biochemical pathways taking place in tissues other than the liver.

This study is designed to test the efficacy and safety of IV Ammonul® as a treatment for acute episodes of elevated ammonia in patients with Grade 3 or 4 HE. Study was terminated due to lack of enrollment and business decisions.


Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland

Current Primary Outcome: Efficacy, as Assessed by Time to Grade 2 or Less in the West Haven Criteria Sustaining for 4 Hours or Longer [ Time Frame: Time to Grade 2 or less sustaining for 4 hours or longer ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Safety, as Assessed by Reported Adverse Events, Clinical Laboratory Measurements, Changes in Vital Signs, and Changes in 12-lead ECG Results [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Proportion of Assessments With a 2-grade Improvement, Using West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Proportion of Assessments With 1-grade Improvement, Using West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Time Spent in an Improved State by 1 or 2 Grades Using the West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Percentage of Subjects With a 1 or 2 Grade Improvement, Using the West Haven Criteria [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 96 hours ]
  • Efficacy, as Assessed by Severity of Hepatic Encephalopathy Using the Glasgow Coma Scale [ Time Frame: 96 hours of treatment and follow-up ]
  • Effects of Ammonul® on Blood Ammonia Levels, Amino Acids and Carnitine [ Time Frame: 96 hours of treatment and follow-up ]
  • Pharmacokinetic Characteristics of Ammonul® and Its Metabolites [ Time Frame: Every 24 hours during treatment period of 96 hours ]


Original Secondary Outcome:

  • Safety, as Assessed by Reported Adverse Events, Clinical Laboratory Measurements, Changes in Vital Signs, and Changes in 12-lead ECG Results [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Proportion of Assessments With a 2-grade Improvement, Using West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Proportion of Assessments With 1-grade Improvement, Using West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Time Spent in an Improved State by 1 or 2 Grades Using the West Haven Criteria [ Time Frame: 96 hours of treatment and follow-up ]
  • Efficacy, as Assessed by Percentage of Subjects With a 1 or 2 Grade Improvement, Using the West Haven Criteria [ Time Frame: At any time point and at each specific time point ]
  • Efficacy, as Assessed by Severity of Hepatic Encephalopathy Using the Glasgow Coma Scale [ Time Frame: 96 hours of treatment and follow-up ]
  • Effects of Ammonul® on Blood Ammonia Levels, Amino Acids and Carnitine [ Time Frame: 96 hours of treatment and follow-up ]
  • Pharmacokinetic Characteristics of Ammonul® and Its Metabolites [ Time Frame: Every 24 hours during treatment period of 96 hours ]


Information By: Horizon Pharma Ireland, Ltd., Dublin Ireland

Dates:
Date Received: January 9, 2008
Date Started: December 2007
Date Completion:
Last Updated: March 1, 2016
Last Verified: March 2016