HyperammonemiaPhase 1NCT05349435
A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate
A Phase 1 study testing Fezagepras and Sodium phenylbutyrate in people with Hyperammonemia, run by Liminal BioSciences Ltd. at 1 site in United Kingdom.
Trial summary
The purpose of this study is to compare the safety, tolerability and pharmacokinetic profile of fezagepras (PBI-4050) to that of sodium phenylbutyrate (PBA) when both products are given as single ascending doses to healthy adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperammonemia
- What is being tested?
- Fezagepras and Sodium phenylbutyrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 May 2022to 30 Jun 2022
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy, adult, male or female (of non childbearing potential only*), 18 to 65 years of age, inclusive, at the screening visit.
- Females of childbearing potential are defined as fertile, following menarche and until becoming post menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- Females of non-childbearing potential are defined as females who have undergone a sterilization procedure at least 6 months prior to the first dosing or females who are postmenopausal.
- Male subjects must follow protocol specified contraception guidance
- Continuous non smoker who has not used nicotine and tobacco containing products for at least 3 months prior to the first dosing based on subject self-reporting.
- Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 and body weight of ≥ 50 kg for males and ≥ 45.0 kg for females, at the screening visit.
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- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs and ECGs, as deemed by the PI or designee, including the following:
- Seated blood pressure is ≥ 90/40 mmHg and ≤ 140/90 mmHg at the screening visit.
- Seated heart rate is ≥ 40 bpm and ≤ 99 bpm at the screening visit.
- QTcF interval is ≤ 460 msec (males) and ≤ 470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit.
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min at the screening visit.
- Hemoglobin ≥ 128 g/L (males) or ≥ 115 g/L (females) and hematocrit ≥ 0.36 L/L (males) or ≥ 0.32 L/L (females) at screening.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ upper limit of normal (ULN), total bilirubin ≤ 2 ULN or creatinine is ≤ ULN.
- Able to swallow multiple tablets.
- Understands the study procedures in the informed consent form (ICF), able to provide written consent and be willing and able to comply with the protocol to completion of the study (including follow-up visit).
Who cannot join
- Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- History or presence of clinically significant medical or psychiatric condition or disease, including but not limited to neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- History of any illness that might confound the results of the study or pose an additional risk to the subject by their participation in the study.
- History of significant drug abuse within 18 months prior to screening or use of soft drugs (such as marijuana) within 6 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 18 months prior to screening.
- Drink alcohol in excess of 21 units per week for males or 14 glasses/units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
- History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
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- History or presence of:
- Clinically significant allergic reactions (e.g., anaphylactic reaction and angioedema) to any drug at the discretion of the PI or designee.
- Clinically significant illness or surgery within 4 weeks prior to dosing at the discretion of the PI or designee. Subjects vomiting within 24 hours pre-dose will be carefully evaluated for upcoming illness/disease. Inclusion pre-dosing is at the discretion of the PI or designee.
- Female subjects of childbearing potential.
- Female subject with a positive pregnancy test at the screening visit or at check in or who are lactating.
- Positive urine drug or alcohol results at the screening visit or check in.
- Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at the screening visit.
- Unable to refrain from or anticipates the use of:
- Over-the-counter products and natural health products (including herbal remedies, homeopathic medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to dosing
- Any drugs, including prescription and non prescription medications beginning 14 days prior to the first dosing.
- Any drugs known to be significant inducers of CYP2C9 enzymes and/or P-gp, including St. John's Wort, for 28 days prior to the first dosing
- Any depot injection or an implant of any drug within 3 months prior to first dosing.
- Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing.
- Donation of blood (e.g approximately 500 mL) or plasma within 60 days prior to the first dosing.
- Donation of bone marrow within the last 6 months prior to the first dosing.
- Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first (if applicable) dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first (if applicable) dosing, or concomitant participation in an investigational study involving no drug or device administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomised, Open-Label, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of PBI-4050 Compared to Sodium Phenylbutyrate in Healthy Subjects
The purpose of this study is to compare the safety, tolerability and pharmacokinetic profile of fezagepras (PBI-4050) to that of sodium phenylbutyrate (PBA) when both products are given as single ascending doses to healthy adult subjects.
- Conditions
- Hyperammonemia
- Being tested
- Fezagepras, Sodium phenylbutyrate
- Medical subject headings
- Hyperammonemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FezageprasDrug
Also called PBI-4050
Investigational drug
Sodium phenylbutyrateDrug
Investigational drug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Dose Level 1 | Experimental | Drug: Fezagepras and sodium PBA Receives: Drug: Fezagepras; Drug: Sodium phenylbutyrate |
| Cohort 2 Dose Level 2 | Experimental | Drug: Fezagepras and sodium PBA Receives: Drug: Fezagepras; Drug: Sodium phenylbutyrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Number and Severity of Treatment Emergent Adverse Events
Measured: Day -2 to Day 8 (+/- 3 days)
Secondary outcomes (3)
AUC
Area under the concentration-time curve
Measured: Day 1 and Day 3
Cmax
Maximum plasma concentration
Measured: Day 1 and Day 3
Tmax
Time to reach maximum plasma concentration
Measured: Day 1 and Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2022
- Study start13 May 2022
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Why it stopped: Sponsor has decided to discontinue development of fezegepras based on initial pharmacokinetic results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperammonemiaStudies of the same condition, open and under way.
- 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liminal BioSciences Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sami Omar, Study director, Liminal BioSciences Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05349435
- Sponsor's protocol ID
- PBI-4050-CT-9-21
- Status last verified
- Jul 2022
- First submitted
- 21 Apr 2022
- Last updated
- 1 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomised, Open-Label, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of PBI-4050 Compared to Sodium Phenylbutyrate in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05349435
- Acronym / sponsor ID
- PBI-4050-CT-9-21
- Conditions
- Hyperammonemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor has decided to discontinue development of fezegepras based on initial pharmacokinetic results
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Liminal BioSciences Ltd.Industry (pharma, biotech, devices)
- Study start
- 13 May 2022 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 27 Apr 2022 (actual)
- 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 compare the safety, tolerability and pharmacokinetic profile of fezagepras (PBI-4050) to that of sodium phenylbutyrate (PBA) when both products are given as single ascending doses to healthy adult subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Dose Level 1 | Experimental | Drug: Fezagepras, Drug: Sodium phenylbutyrateDrug: Fezagepras and sodium PBA |
| Cohort 2 Dose Level 2 | Experimental | Drug: Fezagepras, Drug: Sodium phenylbutyrateDrug: Fezagepras and sodium PBA |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Healthy, adult, male or female (of non childbearing potential only*), 18 to 65 years of age, inclusive, at the screening visit.
- Male subjects must follow protocol specified contraception guidance
- Continuous non smoker who has not used nicotine and tobacco containing products for at least 3 months prior to the first dosing based on subject self-reporting.
- Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 and body weight of ≥ 50 kg for males and ≥ 45.0 kg for females, at the screening visit.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs and ECGs, as deemed by the PI or designee, including the following:
Key exclusion criteria (22 listed)
- Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- History or presence of clinically significant medical or psychiatric condition or disease, including but not limited to neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- History of any illness that might confound the results of the study or pose an additional risk to the subject by their participation in the study.
- History of significant drug abuse within 18 months prior to screening or use of soft drugs (such as marijuana) within 6 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 18 months prior to screening.
- Drink alcohol in excess of 21 units per week for males or 14 glasses/units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
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 |
|---|---|---|
| FezageprasAlso: PBI-4050Investigational drug | Drug | Cohort 1 Dose Level 1, Cohort 2 Dose Level 2 |
| Sodium phenylbutyrateInvestigational drug | Drug | Cohort 1 Dose Level 1, Cohort 2 Dose Level 2 |
Primary outcome
Safety and tolerability
Time frame: Day -2 to Day 8 (+/- 3 days)
Number and Severity of Treatment Emergent Adverse Events
3 secondary outcomes
AUC
Time frame: Day 1 and Day 3
Cmax
Time frame: Day 1 and Day 3
Tmax
Time frame: Day 1 and Day 3
Results and safety
The study was stopped early (reason given: Sponsor has decided to discontinue development of fezegepras based on initial pharmacokinetic results). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
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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.
Sami Omar study director
Liminal BioSciences Ltd.
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 Fezagepras and Sodium phenylbutyrate in people with Hyperammonemia, run by Liminal BioSciences Ltd. at 1 site in United Kingdom.
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 22 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 1 Aug 2022. 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 United Kingdom. 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 was stopped early (reason given: Sponsor has decided to discontinue development of fezegepras based on initial pharmacokinetic results). Results are not available in the source record.
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?
Safety and tolerability (time frame: Day -2 to Day 8 (+/- 3 days)). 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 1 Aug 2022.