Clinical trial NCT04068259: Single Ascending Dose Study of PBI-4547 in Healthy Subjects
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of PBI-4547 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Liminal BioSciences Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2019-08-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: 5-6 days
measure: Number of participants with clinically significant laboratory evaluation findings
timeFrame: 5-6 days
measure: Number of participants with clinically significant electrocardiogram (ECG) Findings
timeFrame: 5-6 days
measure: Number of participants with clinically significant vital sign findings
timeFrame: 5-6 days
measure: Number of participants with physical examination findings
timeFrame: 5-6 days
Secondary outcomes:
measure: AUC0-t for PBI-4547
timeFrame: 48 hours
measure: AUC0-inf for PBI-4547
timeFrame: 48 hours
measure: Cmax for PBI-4547
timeFrame: 48 hours
measure: Residual area for PBI-4547
timeFrame: 48 hours
measure: Tmax for PBI-4547
timeFrame: 48 hours
measure: T1/2 el for PBI-4547
timeFrame: 48 hours
measure: Kel for PBI-4547
timeFrame: 48 hours
measure: Rkel for PBI-4547
timeFrame: 48 hours
measure: MRT for PBI-4547
timeFrame: 48 hours
measure: Cl/F for PBI-4547
timeFrame: 48 hours
measure: Vd/F for PBI-4547
timeFrame: 48 hours
measure: AUC0-t for PBI-4547 under fed condition
timeFrame: 48 hours
measure: AUC0-inf for PBI-4547 under fed condition
timeFrame: 48 hours
measure: Cmax for PBI-4547 under fed condition
timeFrame: 48 hours
measure: Tmax for PBI-4547 under fed condition
timeFrame: 48 hours
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Syneos Health
state: Quebec
city: Québec
country: Canada
facility: Syneos Health
Study officials:
affiliation: Prometic Pharma SMT Ltd.
name: John Moran, MD
role: STUDY_DIRECTOR
affiliation: Syneos Health
name: Richard Larouche, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leduc M, Grouix B, Tremblay M, GervaisL, Sarra-Bournet F, Felton X, Simard J, Leblond FA, Laurin P and Gagnon L. PBI-4547 Improves Glucose Metabolism and Insulin Resistance, and Reduces Liver Damage in a High-Fat Diet Mouse Model of Obesity and Metabolic Syndrome. Diabetes 2018 Jul; 67(Supplement 1).
citation: Gagnon L, Laverdure A, Sarra-Bournet F, Cloutier M, Felton A, Treemblay M, Richard J, Gervais L, Laurin P, Leblond FA and Grouix B. PBI-4547 Reverses Diabetes and Metabolic Syndrome through Regulation of Lipid/Glucose Metabolism, ß-Oxidation and Fibrosis in Liver, and White Adipose Tissue in ob/ob Mice. Diabetes 2018 Jul; 67(Supplement 1).
citation: Sarra-Bournet F, Grouix B, Hince K, Felton A, Tremblay M, Abbott S, Duceppe JS, Zacharie B, Laurin P, Gagnon G. PBI-4547 decreases hepatic stellate cell activation via AMPK signaling pathway, and reduces fibrosis in carbon tetrachloride (CCL4)-induced hepatic fibrosis model. Journal of Hepatology 2018, 68:S365-S604.