HealthyPhase 1NCT00977600
A Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
A Phase 1 study testing HPN-100, Ammonul and Buphenyl in people with Healthy, run by Amgen at 1 site in Ukraine.
Trial summary
To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- HPN-100, Ammonul and Buphenyl
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUkraine
- Study dates
- Mar 2005to Jul 2005
- 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 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects were required to fulfill the following criteria in order to participate in the study:
- Males aged 18 to 45 years of age
- Ability 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
- Subjects who were in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, 12 lead ECG, and vital signs
- Weight within the range of 60-120 kg
Who cannot join
- Subjects who fulfilled any of the following criteria were excluded from the study:
- Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurologic, immunologic, or psychiatric disorder(s), as determined by the investigator
- Clinically significant abnormal laboratory values (as determined by the investigator)
- Significant illness within 14 days prior to screening
- Any disorder that might significantly interfere with the absorption, distribution, metabolism, or excretion of any drug
- Use of any prescription medication within 14 days prior to screening
Show all 16Show fewer
- Use of dietary supplements, herbal medicines, vitamins, or over-the-counter medication(s) (with the exception of acetaminophen ≤ 500 mg/day) within 10 days prior to first dosing
- Positive drugs of abuse urine test at screening or pre-dose day (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, methadone)
- Positive alcohol breath test at screening or pre-dose day
- Donation or loss of blood (500 ml or more) within 30 days prior to first dosing, or during the study
- Donation or loss of plasma within 7 days prior to first dosing, or during the study
- History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC)
- History of acquired immunodeficiency syndrome (AIDS) or determined HIV positive at screening
- Use of any investigational drug within 12 weeks prior to first dosing
- Known hypersensitivity to sodium phenylbutyrate or similar drugs
- Previous exposure to sodium phenylbutyrate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects.
Read the detailed description
A randomized, open-label, four-treatment, four-period crossover study in which healthy male subjects received a single dose of each of the following four treatments on four separate dosing days, 7 days apart:
- Oral sodium phenylbutyrate (Buphenyl®) equivalent to 3 g/m2 of 4-phenylbutyric acid (PBA) per dose
- Oral GT4P-F mole equivalents to 3 g/m2 of PBA per dose
- Oral GT4P-API mole equivalents to 3 g/m2 of PBA per dose
- Intravenous 10% sodium phenylacetate plus 10% sodium benzoate (Ammonul®) 2.75 g/m2
Study acquired from Horizon in 2024.
- Conditions
- Healthy
- Being tested
- HPN-100, Ammonul, Buphenyl
- Keywords
- Ammonul, Sodium phenylacetate, sodium benzoate, Buphenyl, sodium phenylbutyrate, HPN-100, GT4P, Glyceryl tri-(4-phenylbutyrate), Healthy Volunteers
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 Buphenyl. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbutyric acid (PBA). PBA is converted to phenyl acetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers equivalent amount of PBA that 40 tablets of NaPBA do.
AmmonulDrug
BuphenylDrug
| Study group | Role | What they receive |
|---|---|---|
| GT4P-F | Experimental | GT4P-F (80% GT4P) was supplied as an odorless, colorless, tasteless liquid oil in 125 ml bottles. This formulation was designed to be mixed in water and create a self-emulsifying suspension, thus administered in water for the trial. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-F was mixed in 50 ml of water, taken orally, and then the cup rinsed with 50 ml of water and taken orally. GT4P-F was stored at ambient temperature away from light. Receives: Drug: HPN-100 |
| GT4P-API | Experimental | GT4P-API was supplied as an odorless, colorless, tasteless oil in 125 ml bottles. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-API was taken orally and washed down with 100 ml of water. GT4P-API was stored at ambient temperature, away from light. Receives: Drug: HPN-100 |
| Ammonul | Active comparator | Ammonul® was supplied as single-use glass vials of 10% sodium phenylacetate and 10% sodium benzoate for intravenous injection. Ammonul® was diluted before use with sterile dextrose injection 10% to a concentration of 9 mg/ml. Once diluted it was kept at room temperature and used within 24 hours. The dose was 2.75 g/m2 and was administered as an intravenous infusion over a 120-minute period. Ammonul® was stored at 25°C, within a range of 15-30°C. Receives: Drug: Ammonul |
| Buphenyl | Active comparator | Sodium phenylbutyrate or Buphenyl® was supplied as a white powder in 250 g bottles. The required amount of powder (equivalent to 3 g/m2 of PBA) was weighed out, mixed in 100 ml of water, and administered orally. Doses were calculated on a weight/volume basis and corrected for sodium content and purity. Buphenyl® was stored at ambient temperature. Receives: Drug: Buphenyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of adverse events
Measured: 33 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2009 (estimated)
- Study startMar 2005
- Study completionJul 2005
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 HealthyStudies 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT00977600
- Sponsor's protocol ID
- UP 1204-001
- Status last verified
- Jun 2024
- First submitted
- 15 Sep 2009
- Last updated
- 20 Jun 2024
- Results posted
- No
- Data monitoring committee
- 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 Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
- ClinicalTrials.gov ID
- NCT00977600
- Acronym / sponsor ID
- UP 1204-001
- Conditions
- Healthy
- Keywords
- Ammonul, Sodium phenylacetate, sodium benzoate, Buphenyl, sodium phenylbutyrate, HPN-100, GT4P, Glyceryl tri-(4-phenylbutyrate)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Ucyclyd Pharma, Inc.
- Study start
- Mar 2005
- Study completion
- Jul 2005 (actual)
- First posted
- 16 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.
To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects.
Detailed description
A randomized, open-label, four-treatment, four-period crossover study in which healthy male subjects received a single dose of each of the following four treatments on four separate dosing days, 7 days apart:
- Oral sodium phenylbutyrate (Buphenyl®) equivalent to 3 g/m2 of 4-phenylbutyric acid (PBA) per dose
- Oral GT4P-F mole equivalents to 3 g/m2 of PBA per dose
- Oral GT4P-API mole equivalents to 3 g/m2 of PBA per dose
- Intravenous 10% sodium phenylacetate plus 10% sodium benzoate (Ammonul®) 2.75 g/m2
Study acquired from Horizon in 2024.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GT4P-F | Experimental | Drug: HPN-100GT4P-F (80% GT4P) was supplied as an odorless, colorless, tasteless liquid oil in 125 ml bottles. This formulation was designed to be mixed in water and create a self-emulsifying suspension, thus administered in water for the trial. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-F was mixed in 50 ml of water, taken orally, and then the cup rinsed with 50 ml of water and taken orally. GT4P-F was stored at ambient temperature away from light. |
| GT4P-API | Experimental | Drug: HPN-100GT4P-API was supplied as an odorless, colorless, tasteless oil in 125 ml bottles. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-API was taken orally and washed down with 100 ml of water. GT4P-API was stored at ambient temperature, away from light. |
| Ammonul | Active comparator | Drug: AmmonulAmmonul® was supplied as single-use glass vials of 10% sodium phenylacetate and 10% sodium benzoate for intravenous injection. Ammonul® was diluted before use with sterile dextrose injection 10% to a concentration of 9 mg/ml. Once diluted it was kept at room temperature and used within 24 hours. The dose was 2.75 g/m2 and was administered as an intravenous infusion over a 120-minute period. Ammonul® was stored at 25°C, within a range of 15-30°C. |
| Buphenyl | Active comparator | Drug: BuphenylSodium phenylbutyrate or Buphenyl® was supplied as a white powder in 250 g bottles. The required amount of powder (equivalent to 3 g/m2 of PBA) was weighed out, mixed in 100 ml of water, and administered orally. Doses were calculated on a weight/volume basis and corrected for sodium content and purity. Buphenyl® was stored at ambient temperature. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Subjects were required to fulfill the following criteria in order to participate in the study:
- Males aged 18 to 45 years of age
- Ability 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
- Subjects who were in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, 12 lead ECG, and vital signs
- Weight within the range of 60-120 kg
Key exclusion criteria (16 listed)
- Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurologic, immunologic, or psychiatric disorder(s), as determined by the investigator
- Clinically significant abnormal laboratory values (as determined by the investigator)
- Significant illness within 14 days prior to screening
- Any disorder that might significantly interfere with the absorption, distribution, metabolism, or excretion of any drug
- Use of any prescription medication within 14 days prior to screening
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 Buphenyl. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbutyric acid (PBA). PBA is converted to phenyl acetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers equivalent amount of PBA that 40 tablets of NaPBA do. | Drug | GT4P-API, GT4P-F |
| Ammonul | Drug | Ammonul |
| Buphenyl | Drug | Buphenyl |
Primary outcome
The rate of adverse events
Time frame: 33 Days
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
1 site 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, Ammonul and Buphenyl in people with Healthy, run by Amgen at 1 site 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 5 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: 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 1 site 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 events (time frame: 33 Days). 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 NCT00977600, 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.