Hepatic EncephalopathyPhase 2NCT00597909
Efficacy and Safety Study of Ammonul® in Patients With Grade 3 or 4 Hepatic Encephalopathy
A Phase 2 study testing sodium phenylacetate and sodium benzoate injection 10% / 10% in people with Hepatic Encephalopathy, run by Amgen at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- sodium phenylacetate and sodium benzoate injection 10% / 10%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2007to Sep 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UCSF-Fresno University
Fresno, California, 93721
Loma Linda University Medical Center
Loma Linda, California, 92354
Permian Research Foundation
Odessa, Texas, 79761
About this study
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 Grade 3 or 4 Hepatic Encephalopathy
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).
Read the detailed description
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.
Study with completed results acquired from Horizon in 2024
- Conditions
- Hepatic Encephalopathy
- Being tested
- sodium phenylacetate and sodium benzoate injection 10% / 10%, placebo solution (10% dextrose)
- Keywords
- Ammonul®, sodium phenylacetate and sodium benzoate, hepatic encephalopathy, Grade 3 or 4 Hepatic Encephalopathy
- Medical subject headings
- Hepatic Encephalopathy, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium phenylacetate and sodium benzoate injection 10% / 10%Drug
Also called Ammonul®
5.5 g/m² diluted in 10% dextrose, IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours)
sodium phenylacetate and sodium benzoate injection 10% / 10%Drug
Also called Ammonul®
2.75 g/m² diluted in 10% dextrose, IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours)
placebo solution (10% dextrose)Drug
Placebo solution (10% dextrose), IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: sodium phenylacetate and sodium benzoate injection 10% / 10% |
| Arm 2 | Experimental | Not described Receives: Drug: sodium phenylacetate and sodium benzoate injection 10% / 10% |
| Arm 3 | Placebo comparator | Not described Receives: Drug: placebo solution (10% dextrose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy, as Assessed by Time to Grade 2 or Less in the West Haven Criteria Sustaining for 4 Hours or Longer
Measured: Time to Grade 2 or less sustaining for 4 hours or longer
Secondary outcomes (8)
Safety, as Assessed by Reported Adverse Events, Clinical Laboratory Measurements, Changes in Vital Signs, and Changes in 12-lead ECG Results
Measured: 96 hours of treatment and follow-up
Efficacy, as Assessed by Proportion of Assessments With a 2-grade Improvement, Using West Haven Criteria
Measured: 96 hours of treatment and follow-up
Efficacy, as Assessed by Proportion of Assessments With 1-grade Improvement, Using West Haven Criteria
Measured: 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
Measured: 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
Measured: 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
Measured: 96 hours of treatment and follow-up
Effects of Ammonul® on Blood Ammonia Levels, Amino Acids and Carnitine
Measured: 96 hours of treatment and follow-up
Pharmacokinetic Characteristics of Ammonul® and Its Metabolites
Measured: Every 24 hours during treatment period of 96 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2008 (estimated)
- Study startDec 2007
- Primary completionSep 2008
- Study completionSep 2008
Why it stopped: Study was terminated due to lack of enrollment and business decisions.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00597909
- Sponsor's protocol ID
- HYP1203-004
- Status last verified
- Nov 2024
- First submitted
- 9 Jan 2008
- Last updated
- 17 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Grade 3 or 4 Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT00597909
- Acronym / sponsor ID
- HYP1203-004
- Conditions
- Hepatic Encephalopathy
- Keywords
- Ammonul®, sodium phenylacetate and sodium benzoate, hepatic encephalopathy, Grade 3 or 4 Hepatic Encephalopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to lack of enrollment and business decisions.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 18 Jan 2008 (estimated)
- Results
- Posted 31 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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.
Study with completed results acquired from Horizon in 2024
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: sodium phenylacetate and sodium benzoate injection 10% / 10% |
| Arm 2 | Experimental | Drug: sodium phenylacetate and sodium benzoate injection 10% / 10% |
| Arm 3 | Placebo comparator | Drug: placebo solution (10% dextrose) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium phenylacetate and sodium benzoate injection 10% / 10%Also: Ammonul®5.5 g/m² diluted in 10% dextrose, IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours) | Drug | Arm 1 |
| sodium phenylacetate and sodium benzoate injection 10% / 10%Also: Ammonul®2.75 g/m² diluted in 10% dextrose, IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours) | Drug | Arm 2 |
| placebo solution (10% dextrose)Placebo solution (10% dextrose), IV as a 2-hour loading (initial) dose, followed by the same dose over 24 hours (maintenance infusion); maintenance infusion will be continued for 3 days (70 hours) | Drug | Arm 3 |
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
8 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Medline Plus: Brain DiseasesLink provided by the sponsor.
- Medline Plus: CirrhosisLink provided by the sponsor.
- Medline Plus: HepatitisLink provided by the sponsor.
- Medline Plus: Liver DiseasesLink provided by the sponsor.
- Medline Plus: Metabolic DisordersLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sodium phenylacetate and sodium benzoate injection 10% / 10% in people with Hepatic Encephalopathy, run by Amgen at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.