Hepatic EncephalopathyPhase 1NCT00986895
A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group
A Phase 1 study testing HPN-100 in people with Hepatic Encephalopathy and Urea Cycle Disorders, run by Amgen at 2 sites in Ukraine.
Trial summary
The purpose of this study is to determine the safety and tolerability of GT4P administered orally as a single dose, and twice daily for 7 consecutive days, to subjects with hepatic impairment with cirrhosis (Child-Pugh scores of A, B, or C) and to a gender matched and similar age control group with normal hepatic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy, Urea Cycle Disorders
- What is being tested?
- HPN-100
- Type of treatment
- Pill or oral medicine
- How many people
- 32 participants
- Where
- 2 sitesUkraine
- Study dates
- Sep 2006to Jun 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects were required to fulfill the following criteria in order to participate in the study:
- Screening:
- Males or females aged ≥ 18 years of age
- Able to provide written informed consent before any study-related procedures, and ability, in the opinion of the Investigator, to comply with all the requirements of the study
- Classification to one of the following:
- current diagnosis of hepatic impairment with cirrhosis
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- healthy subject
- Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups:
- Child-Pugh score A
- Child-Pugh score B
- Child-Pugh score C
- Subjects with hepatic impairment with cirrhosis who were on a therapeutic regimen of lactulose must have been on a stable dose for ≥ 30 days prior to screening
- If female, a negative pregnancy test at screening and pre-dose on day 0, or a documented sterilization procedure; a female of child-bearing potential must have been using a medically approved birth control method and must have agreed to use the same method of contraception during the full course of the study (on pre-dose day 0 as well as at screening)
- Weight within the range of 60-100 kg (at screening and pre-dose on day 0)
- Willing to stop taking any medication that the Sponsor and the Investigator felt was not appropriate for use during the study, beginning 2 days before dosing and throughout the study
Who cannot join
- Subjects who fulfilled any of the following criteria were excluded from the study:
- Screening:
- Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator
- Serum sodium < 120 mEq/L
- Serum creatinine ≥ 1.5 upper limit of normal
- Potassium ≤ 3.5 mEq/L
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- Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator
- Significant illness within the last 14 days
- Oral temperature > 38.5°C or < 36°C and/or a suspected site of active infection
- Inflammatory bowel disease or malabsorption defined with steatorrhea
- Active gastrointestinal bleeding, defined as melena, hematochezia, or hematemesis requiring hospitalization within the last 30 days
- Use of probenecid, valproate, or corticosteroids within the last 24 hours
- Use of any medication, other than those approved by the Sponsor and Investigator, in the last 48 hours
- History of seizures within the last 72 hours
- Positive drugs of abuse urine test
- Positive alcohol breath test
- Donation or loss of blood (500 mL or more) within the last 30 days
- Donation or loss of plasma within the last 7 days
- History of acquired immunodeficiency syndrome (AIDS) or determined human immunodeficiency virus (HIV) positive
- Hepatitis B or C (HBV; HCV) positive (healthy volunteers only)
- Use of any investigational drug within the last 30 days
- Known hypersensitivity to sodium phenylbutyrate or similar drugs
- Emergency hospitalization within the last 90 days
- Intake of alcohol in the last 7 days
- Pre-dose (days 0 and 7):
- Significant illness or emergency hospitalization since the last study visit
- Oral temperature > 38.5°C or < 36°C and/or a suspected site of active infection
- Use of probenecid, valproate, or corticosteroids within the last 24 hours
- Use of any non-approved medication (by the Sponsor/Investigator) within the 48 hours before dosing
- History of seizures within the last 72 hours
- Positive drugs of abuse urine test
- Positive alcohol breath test
- Donation or loss of blood (500 mL or more) or plasma since the last study visit
- Use of any investigational drug since the last study visit
- Intake of alcohol in the last 7 days
Trial locations and contacts
2 sites in 1 country.
Ukraine2 sites
National University of Pharmacy
Kharkiv, 61057
Department of General Surgery #2; Kharkiv State Medical University
Kharkiv, 61128
About this study
The purpose of this study is to determine the safety and tolerability of GT4P administered orally as a single dose, and twice daily for 7 consecutive days, to subjects with hepatic impairment with cirrhosis (Child-Pugh scores of A, B, or C) and to a gender matched and similar age control group with normal hepatic function.
Read the detailed description
Study acquired from Horizon in 2024.
- Conditions
- Hepatic Encephalopathy, Urea Cycle Disorders
- Being tested
- HPN-100
- Keywords
- HPN-100, GT4P, Glyceryl tri-(4-phenylbutyrate)
- Medical subject headings
- Hepatic Encephalopathy, Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HPN-100Drug
HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbuteric acid (PBA). PBA is converted to phenylacetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers an equivalent amount of PBA to40 tablets of NaPBA.
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of adverse event
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2009 (estimated)
- Study startSep 2006
- Study completionJun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ucyclyd Pharma, Inc.
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00986895
- Sponsor's protocol ID
- UP 1204-002
- Status last verified
- Jun 2024
- First submitted
- 15 Sep 2009
- Last updated
- 20 Jun 2024
- Results posted
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
McGuire BM, Zupanets IA, Lowe ME, Xiao X, Syplyviy VA, Monteleone J, Gargosky S, Dickinson K, Martinez A, Mokhtarani M, Scharschmidt BF. Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis. Hepatology. 2010 Jun;51(6):2077-85. doi: 10.1002/hep.23589.
PubMed 20512995
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group
- ClinicalTrials.gov ID
- NCT00986895
- Acronym / sponsor ID
- UP 1204-002
- Conditions
- Hepatic Encephalopathy, Urea Cycle Disorders
- Keywords
- HPN-100, GT4P, Glyceryl tri-(4-phenylbutyrate)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Ucyclyd Pharma, Inc.
- Study start
- Sep 2006
- Study completion
- Jun 2007 (actual)
- First posted
- 30 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and tolerability of GT4P administered orally as a single dose, and twice daily for 7 consecutive days, to subjects with hepatic impairment with cirrhosis (Child-Pugh scores of A, B, or C) and to a gender matched and similar age control group with normal hepatic function.
Detailed description
Study acquired from Horizon in 2024.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects were required to fulfill the following criteria in order to participate in the study:
- Males or females aged ≥ 18 years of age
- Able to provide written informed consent before any study-related procedures, and ability, in the opinion of the Investigator, to comply with all the requirements of the study
- Classification to one of the following:
- Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups:
Key exclusion criteria (35 listed)
- Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator
- Serum sodium < 120 mEq/L
- Serum creatinine ≥ 1.5 upper limit of normal
- Potassium ≤ 3.5 mEq/L
- Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator
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 |
|---|---|---|
| HPN-100HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbuteric acid (PBA). PBA is converted to phenylacetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers an equivalent amount of PBA to40 tablets of NaPBA. | Drug | – |
Primary outcome
The rate of adverse event
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Derived from this study: PubMed 20512995McGuire BM, Zupanets IA, Lowe ME, Xiao X, Syplyviy VA, Monteleone J, Gargosky S, Dickinson K, Martinez A, Mokhtarani M, Scharschmidt BF. Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis. Hepatology. 2010 Jun;51(6):2077-85. doi: 10.1002/hep.23589.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HPN-100 in people with Hepatic Encephalopathy and Urea Cycle Disorders, run by Amgen at 2 sites in Ukraine.
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 15 inclusion and 35 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: finished, as of the sponsor's last update on 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ukraine. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The rate of adverse event. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00986895, which also lists 1 linked publication.
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 20 Jun 2024.