A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate

NCT05349435 | Terminated Phase 1

• 1 other identifier: PBI-4050-CT-9-21
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hyperammonemia

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Number and Severity of Treatment Emergent Adverse Events

  Day -2 to Day 8 (+/- 3 days)

Secondary Outcomes (3)

• AUC

  Day 1 and Day 3

• Cmax

  Day 1 and Day 3

• Tmax

  Day 1 and Day 3

Study Arms (2)

Cohort 1 Dose Level 1

EXPERIMENTAL

Drug: Fezagepras and sodium PBA

Drug: Fezagepras; Drug: Sodium phenylbutyrate

Cohort 2 Dose Level 2

EXPERIMENTAL

Drug: Fezagepras and sodium PBA

Drug: Fezagepras; Drug: Sodium phenylbutyrate

Interventions

Fezagepras DRUG

Investigational drug

Also known as: PBI-4050

Cohort 1 Dose Level 1; Cohort 2 Dose Level 2

Sodium phenylbutyrate DRUG

Investigational drug

Cohort 1 Dose Level 1; Cohort 2 Dose Level 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Liminal BioSciences Ltd.: lead

Study Sites (1)

Celerion

Belfast, Northern Ireland, BT9 6AD, United Kingdom

Location

MeSH Terms

Conditions

Hyperammonemia

Interventions

setogepram; 4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sami Omar

  Liminal BioSciences Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: April 27, 2022
• Study Start: May 13, 2022
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: August 1, 2022

Record last verified: 2022-07

Locations

GB (1)