Single Ascending Dose Study of PBI-4547 in Healthy Subjects
- Registration Number
- NCT04068259
- Lead Sponsor
- Liminal BioSciences Ltd.
- Brief Summary
This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of PBI-4547 in healthy adult participants.
- Detailed Description
This is a first-in-human, single-ascending dose study of PBI-4547 in healthy adult participants. PBI-4547 is a synthetic ligand of G protein-coupled receptor (GPR)40 and GPR84, which have been reported to play a role in fibrosis in various animal models as well as in tissue culture.
A total of 40 healthy adult participants will sequentially receive 1 of 5 doses of PBI-4547 (Dose1, 2, 3, 4 or 5) or matching placebo, with each cohort of 8 participants randomized in a 3:1 ratio to receive PBI-4547 or matching placebo.
A food-effect cohort will be added after review of the PK results of at least the first dose, and the following 2 doses, if needed. In this cohort participants will initially receive the study drug under fasting conditions (Period 1) followed by the same dose after the ingestion of a high-fat meal (Period 2) after a 14-day washout period.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 24
- Healthy male participants or non-childbearing potential female participants, ≥18 and ≤55 years.
- Body mass index > 18.5 and < 30.0 kg/m^2, and body weight ≥ 50.0 kg for male participants and ≥ 45.0 kg for female participants.
- Continuous non-smoker who has not used tobacco or nicotine-containing products for at least 3 months prior to screening.
- Male participants with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after study drug administration.
- Male participants must be willing not to donate sperm until 90 days after study drug administration.
- Any clinically significant abnormality or abnormal laboratory test results.
- An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2.
- Positive urine drug screen and history of significant drug abuse.
- History of significant allergic reactions to any drug.
- Use of any drugs known to induce or inhibit hepatic drug metabolism.
- Positive pregnancy test or breast-feeding participant.
- Clinically significant abnormalities in ECG, blood pressure, and heart rate at screening.
- History of significant alcohol abuse or regular use of alcohol.
- Use of medication other than topical products without significant systemic absorption.
- Donation of plasma.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 4, Dose 4 of PBI-4547 or Placebo Placebo Dose 4 of PBI-4547 or matching Placebo tablets by mouth Cohort 1, Dose 1 of PBI-4547 or Placebo Placebo Dose 1 of PBI-4547 or matching Placebo tablets by mouth Cohort 2, Dose 2 of PBI-4547 or Placebo Placebo Dose 2 of PBI-4547 or matching Placebo tablets by mouth Cohort 3, Dose 3 of PBI-4547 or Placebo Placebo Dose 3 of PBI-4547 or matching Placebo tablets by mouth Cohort 2, Dose 2 of PBI-4547 or Placebo PBI-4547 Dose 2 of PBI-4547 or matching Placebo tablets by mouth Cohort 1, Dose 1 of PBI-4547 or Placebo PBI-4547 Dose 1 of PBI-4547 or matching Placebo tablets by mouth Cohort 3, Dose 3 of PBI-4547 or Placebo PBI-4547 Dose 3 of PBI-4547 or matching Placebo tablets by mouth Cohort 5, Dose 5 of PBI-4547 or Placebo Placebo Dose 5 of PBI-4547 or matching Placebo tablets by mouth Cohort 4, Dose 4 of PBI-4547 or Placebo PBI-4547 Dose 4 of PBI-4547 or matching Placebo tablets by mouth Cohort 5, Dose 5 of PBI-4547 or Placebo PBI-4547 Dose 5 of PBI-4547 or matching Placebo tablets by mouth
- Primary Outcome Measures
Name Time Method Number of participants with clinically significant laboratory evaluation findings 5-6 days Laboratory tests for hematology, serum chemistry and urinalysis will be performed upon admission, at discharge, and at the follow-up visit (5 ± 1 day post-dose).
Number of participants with clinically significant electrocardiogram (ECG) Findings 5-6 days Triplicate ECG will be performed upon admission, pre-dose, and approximately 1, 2, 8, and 24 hours post-dose, and at the follow-up visit (5 ± 1 day post-dose). Subjects will be continuously monitored using a Holter monitor from approximately 1 hour pre-dose until approximately 24 hours post-dose.
Number of participants with physical examination findings 5-6 days Brief physical examination will be conducted upon admission and at discharge. A complete physical examination will be conducted at screening and follow-up visit.
Number of participants with treatment-emergent adverse events (TEAEs) 5-6 days TEAE is any untoward medical occurrence in a subject who has been administered a pharmaceutical product or not, which does not necessarily have a causal relationship with this treatment.
Number of participants with clinically significant vital sign findings 5-6 days Vital signs include blood pressure, heart rate, respiratory rate, and oral body temperature will be measured upon admission, before discharge from the clinic and at the follow-up visit (5 ± 1 day post-dose).
- Secondary Outcome Measures
Name Time Method Cmax for PBI-4547 48 hours Maximum observed concentration
T1/2 el for PBI-4547 48 hours Elimination half-life
AUC0-inf for PBI-4547 under fed condition 48 hours Area under the concentration-time curve from time zero to infinity (extrapolated) after a high-fat diet
Cmax for PBI-4547 under fed condition 48 hours Maximum observed concentration after a high-fat diet
MRT for PBI-4547 48 hours Mean residence time
Vd/F for PBI-4547 48 hours Apparent volume of distribution, calculated as Dose/(Kel x AUC0-inf). Vd/F normalized for subject body weight in kg will be calculated
AUC0-t for PBI-4547 under fed condition 48 hours Area under the concentration-time curve from time zero to the last non-zero concentration after a high-fat diet
AUC0-t for PBI-4547 48 hours Area under the concentration-time curve from time zero to the last non-zero concentration
Residual area for PBI-4547 48 hours Residual area calculated as 100\*(1- AUC0-t / AUC0-inf)
Tmax for PBI-4547 48 hours Time of observed Cmax
AUC0-inf for PBI-4547 48 hours Area under the concentration-time curve from time zero to infinity (extrapolated)
Kel for PBI-4547 48 hours Elimination rate constant
Cl/F for PBI-4547 48 hours Total body clearance, calculated as Dose/AUC0-inf;Cl/F normalized for subject body weight in kg will be calculated
Rkel for PBI-4547 48 hours Accumulation factor based on elimination rate constant
Tmax for PBI-4547 under fed condition 48 hours Time of observed Cmax after a high-fat diet
Trial Locations
- Locations (1)
Syneos Health
🇨🇦Québec, Canada