Healthy Subjects
Conditions
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.
Interventions
DRUGPBI-4547
PBI-4547 tablet
OTHERPlacebo
Placebo tablet
Sponsors
Syneos Health
Liminal BioSciences Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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). |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T1/2 el for PBI-4547 | 48 hours | Elimination half-life |
| Kel for PBI-4547 | 48 hours | Elimination rate constant |
| Rkel for PBI-4547 | 48 hours | Accumulation factor based on elimination rate constant |
| MRT for PBI-4547 | 48 hours | Mean residence time |
| 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 |
| AUC0-t for PBI-4547 | 48 hours | Area under the concentration-time curve from time zero to the last non-zero concentration |
| 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-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 |
| Tmax for PBI-4547 under fed condition | 48 hours | Time of observed Cmax after a high-fat diet |
| 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-inf for PBI-4547 | 48 hours | Area under the concentration-time curve from time zero to infinity (extrapolated) |
| Cmax for PBI-4547 | 48 hours | Maximum observed 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 |
Countries
Canada
Outcome results
None listed