Single Ascending Dose Study of PBI-4547 in Healthy Subjects

Liminal BioSciences

Status and phase: Terminated; Phase 1

Conditions: Healthy Subjects

Treatments: Other: Placebo; Drug: PBI-4547

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04068259

180271 (Other Identifier)

PBI-4547-CT-9-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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24 participants in 5 patient groups

Cohort 1, Dose 1 of PBI-4547 or Placebo

Experimental group

Description:

Dose 1 of PBI-4547 or matching Placebo tablets by mouth

Treatment:

Drug: PBI-4547

Other: Placebo

Cohort 2, Dose 2 of PBI-4547 or Placebo

Experimental group

Description:

Dose 2 of PBI-4547 or matching Placebo tablets by mouth

Treatment:

Drug: PBI-4547

Other: Placebo

Cohort 3, Dose 3 of PBI-4547 or Placebo

Experimental group

Description:

Dose 3 of PBI-4547 or matching Placebo tablets by mouth

Treatment:

Drug: PBI-4547

Other: Placebo

Cohort 4, Dose 4 of PBI-4547 or Placebo

Experimental group

Description:

Dose 4 of PBI-4547 or matching Placebo tablets by mouth

Treatment:

Drug: PBI-4547

Other: Placebo

Cohort 5, Dose 5 of PBI-4547 or Placebo

Experimental group

Description:

Dose 5 of PBI-4547 or matching Placebo tablets by mouth

Treatment:

Drug: PBI-4547

Other: Placebo