Single Ascending Dose Study of PBI-4547 in Healthy Subjects

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04068259
• Other study ID #: PBI-4547-CT-9-01
• Secondary ID: 180271
• Status: Terminated
• Phase: Phase 1
• Start date: September 5, 2019
• Est. completion date: October 8, 2019

Study information

• Verified date: December 2020
• Source: Liminal BioSciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of PBI-4547 in healthy adult participants.

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 information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: October 8, 2019
• Est. primary completion date: October 8, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• PBI-4547
PBI-4547 tablet

Other:
• Placebo
Placebo tablet

Locations

Country	Name	City	State
Canada	Syneos Health	Montréal	Quebec
Canada	Syneos Health	Québec

Sponsors (2)

Lead Sponsor	Collaborator
Liminal BioSciences Ltd.	Syneos Health

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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).

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).

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (TEAEs)	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.	5-6 days
Primary	Number of participants with clinically significant laboratory evaluation findings	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).	5-6 days
Primary	Number of participants with clinically significant electrocardiogram (ECG) Findings	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.	5-6 days
Primary	Number of participants with clinically significant vital sign findings	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).	5-6 days
Primary	Number of participants with physical examination findings	Brief physical examination will be conducted upon admission and at discharge. A complete physical examination will be conducted at screening and follow-up visit.	5-6 days
Secondary	AUC0-t for PBI-4547	Area under the concentration-time curve from time zero to the last non-zero concentration	48 hours
Secondary	AUC0-inf for PBI-4547	Area under the concentration-time curve from time zero to infinity (extrapolated)	48 hours
Secondary	Cmax for PBI-4547	Maximum observed concentration	48 hours
Secondary	Residual area for PBI-4547	Residual area calculated as 100*(1- AUC0-t / AUC0-inf)	48 hours
Secondary	Tmax for PBI-4547	Time of observed Cmax	48 hours
Secondary	T1/2 el for PBI-4547	Elimination half-life	48 hours
Secondary	Kel for PBI-4547	Elimination rate constant	48 hours
Secondary	Rkel for PBI-4547	Accumulation factor based on elimination rate constant	48 hours
Secondary	MRT for PBI-4547	Mean residence time	48 hours
Secondary	Cl/F for PBI-4547	Total body clearance, calculated as Dose/AUC0-inf;Cl/F normalized for subject body weight in kg will be calculated	48 hours
Secondary	Vd/F for PBI-4547	Apparent volume of distribution, calculated as Dose/(Kel x AUC0-inf). Vd/F normalized for subject body weight in kg will be calculated	48 hours
Secondary	AUC0-t for PBI-4547 under fed condition	Area under the concentration-time curve from time zero to the last non-zero concentration after a high-fat diet	48 hours
Secondary	AUC0-inf for PBI-4547 under fed condition	Area under the concentration-time curve from time zero to infinity (extrapolated) after a high-fat diet	48 hours
Secondary	Cmax for PBI-4547 under fed condition	Maximum observed concentration after a high-fat diet	48 hours
Secondary	Tmax for PBI-4547 under fed condition	Time of observed Cmax after a high-fat diet	48 hours