Ignite Creation Date:
2025-12-24 @ 2:23 PM
Ignite Modification Date:
2026-01-02 @ 2:53 AM
Study NCT ID:
NCT04068259
Status:
TERMINATED
Last Update Posted:
2020-12-08
First Post:
2019-08-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Single Ascending Dose Study of PBI-4547 in Healthy Subjects
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000712519', 'term': 'PBI-4547'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'whyStopped': 'PK data from first 3 cohorts does not support study continuation.There was no safety concerns', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2019-09-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-12', 'completionDateStruct': {'date': '2019-10-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-07', 'studyFirstSubmitDate': '2019-08-22', 'studyFirstSubmitQcDate': '2019-08-22', 'lastUpdatePostDateStruct': {'date': '2020-12-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-08-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-10-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of participants with treatment-emergent adverse events (TEAEs)', 'timeFrame': '5-6 days', 'description': '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.'}, {'measure': 'Number of participants with clinically significant laboratory evaluation findings', 'timeFrame': '5-6 days', 'description': '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).'}, {'measure': 'Number of participants with clinically significant electrocardiogram (ECG) Findings', 'timeFrame': '5-6 days', 'description': '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.'}, {'measure': 'Number of participants with clinically significant vital sign findings', 'timeFrame': '5-6 days', 'description': '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).'}, {'measure': 'Number of participants with physical examination findings', 'timeFrame': '5-6 days', 'description': 'Brief physical examination will be conducted upon admission and at discharge. A complete physical examination will be conducted at screening and follow-up visit.'}], 'secondaryOutcomes': [{'measure': 'AUC0-t for PBI-4547', 'timeFrame': '48 hours', 'description': 'Area under the concentration-time curve from time zero to the last non-zero concentration'}, {'measure': 'AUC0-inf for PBI-4547', 'timeFrame': '48 hours', 'description': 'Area under the concentration-time curve from time zero to infinity (extrapolated)'}, {'measure': 'Cmax for PBI-4547', 'timeFrame': '48 hours', 'description': 'Maximum observed concentration'}, {'measure': 'Residual area for PBI-4547', 'timeFrame': '48 hours', 'description': 'Residual area calculated as 100\\*(1- AUC0-t / AUC0-inf)'}, {'measure': 'Tmax for PBI-4547', 'timeFrame': '48 hours', 'description': 'Time of observed Cmax'}, {'measure': 'T1/2 el for PBI-4547', 'timeFrame': '48 hours', 'description': 'Elimination half-life'}, {'measure': 'Kel for PBI-4547', 'timeFrame': '48 hours', 'description': 'Elimination rate constant'}, {'measure': 'Rkel for PBI-4547', 'timeFrame': '48 hours', 'description': 'Accumulation factor based on elimination rate constant'}, {'measure': 'MRT for PBI-4547', 'timeFrame': '48 hours', 'description': 'Mean residence time'}, {'measure': 'Cl/F for PBI-4547', 'timeFrame': '48 hours', 'description': 'Total body clearance, calculated as Dose/AUC0-inf;Cl/F normalized for subject body weight in kg will be calculated'}, {'measure': 'Vd/F for PBI-4547', 'timeFrame': '48 hours', 'description': 'Apparent volume of distribution, calculated as Dose/(Kel x AUC0-inf). Vd/F normalized for subject body weight in kg will be calculated'}, {'measure': 'AUC0-t for PBI-4547 under fed condition', 'timeFrame': '48 hours', 'description': 'Area under the concentration-time curve from time zero to the last non-zero concentration after a high-fat diet'}, {'measure': 'AUC0-inf for PBI-4547 under fed condition', 'timeFrame': '48 hours', 'description': 'Area under the concentration-time curve from time zero to infinity (extrapolated) after a high-fat diet'}, {'measure': 'Cmax for PBI-4547 under fed condition', 'timeFrame': '48 hours', 'description': 'Maximum observed concentration after a high-fat diet'}, {'measure': 'Tmax for PBI-4547 under fed condition', 'timeFrame': '48 hours', 'description': 'Time of observed Cmax after a high-fat diet'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Healthy Subjects']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', '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).'}, {'type': 'BACKGROUND', '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).'}, {'type': 'BACKGROUND', '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.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of PBI-4547 in healthy adult participants.', 'detailedDescription': '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.\n\nA 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.\n\nA 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy male participants or non-childbearing potential female participants, ≥18 and ≤55 years.\n* 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.\n* Continuous non-smoker who has not used tobacco or nicotine-containing products for at least 3 months prior to screening.\n* 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.\n* Male participants must be willing not to donate sperm until 90 days after study drug administration.\n\nExclusion Criteria:\n\n* Any clinically significant abnormality or abnormal laboratory test results.\n* An estimated glomerular filtration rate (eGFR) \\<60 mL/min/1.73 m\\^2.\n* Positive urine drug screen and history of significant drug abuse.\n* History of significant allergic reactions to any drug.\n* Use of any drugs known to induce or inhibit hepatic drug metabolism.\n* Positive pregnancy test or breast-feeding participant.\n* Clinically significant abnormalities in ECG, blood pressure, and heart rate at screening.\n* History of significant alcohol abuse or regular use of alcohol.\n* Use of medication other than topical products without significant systemic absorption.\n* Donation of plasma.'}, 'identificationModule': {'nctId': 'NCT04068259', 'briefTitle': 'Single Ascending Dose Study of PBI-4547 in Healthy Subjects', 'organization': {'class': 'INDUSTRY', 'fullName': 'Liminal BioSciences Ltd.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'PBI-4547-CT-9-01'}, 'secondaryIdInfos': [{'id': '180271', 'type': 'OTHER', 'domain': 'Syneos Health'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1, Dose 1 of PBI-4547 or Placebo', 'description': 'Dose 1 of PBI-4547 or matching Placebo tablets by mouth', 'interventionNames': ['Drug: PBI-4547', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2, Dose 2 of PBI-4547 or Placebo', 'description': 'Dose 2 of PBI-4547 or matching Placebo tablets by mouth', 'interventionNames': ['Drug: PBI-4547', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 3, Dose 3 of PBI-4547 or Placebo', 'description': 'Dose 3 of PBI-4547 or matching Placebo tablets by mouth', 'interventionNames': ['Drug: PBI-4547', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 4, Dose 4 of PBI-4547 or Placebo', 'description': 'Dose 4 of PBI-4547 or matching Placebo tablets by mouth', 'interventionNames': ['Drug: PBI-4547', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 5, Dose 5 of PBI-4547 or Placebo', 'description': 'Dose 5 of PBI-4547 or matching Placebo tablets by mouth', 'interventionNames': ['Drug: PBI-4547', 'Other: Placebo']}], 'interventions': [{'name': 'PBI-4547', 'type': 'DRUG', 'description': 'PBI-4547 tablet', 'armGroupLabels': ['Cohort 1, Dose 1 of PBI-4547 or Placebo', 'Cohort 2, Dose 2 of PBI-4547 or Placebo', 'Cohort 3, Dose 3 of PBI-4547 or Placebo', 'Cohort 4, Dose 4 of PBI-4547 or Placebo', 'Cohort 5, Dose 5 of PBI-4547 or Placebo']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Placebo tablet', 'armGroupLabels': ['Cohort 1, Dose 1 of PBI-4547 or Placebo', 'Cohort 2, Dose 2 of PBI-4547 or Placebo', 'Cohort 3, Dose 3 of PBI-4547 or Placebo', 'Cohort 4, Dose 4 of PBI-4547 or Placebo', 'Cohort 5, Dose 5 of PBI-4547 or Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'H3X 2H9', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Syneos Health', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'zip': 'G1P 0A2', 'city': 'Québec', 'country': 'Canada', 'facility': 'Syneos Health', 'geoPoint': {'lat': 46.81228, 'lon': -71.21454}}], 'overallOfficials': [{'name': 'John Moran, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Prometic Pharma SMT Ltd.'}, {'name': 'Richard Larouche, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Syneos Health'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Liminal BioSciences Ltd.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Syneos Health', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}