Study to Evaluate Safety, Efficacy of PBI-4050 & Its Effect on Relevant Biomarkers in T2DM Patients With Metabolic Syndrome

A Phase 2, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of PBI-4050 in Type 2 Diabetes Mellitus Patients With Metabolic Syndrome

This is a Phase 2, multi-center, double-blind, placebo-controlled study of the safety and effect of PBI-4050 at doses ranging from 400 mg to 1200 mg on relevant biomarkers in subjects with inadequately-controlled T2DMS on stable background antidiabetic therapy.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus; Metabolic Syndrome
• Intervention / Treatment: Other: Placebo; Drug: PBI-4050

Detailed Description

This Phase 2 study will be performed by 15 sites in Canada. The total duration of study participation for each subject is approximately 20 weeks and comprises 6 study visits

A total of approximately 268 subjects will be enrolled in the study and randomly assigned to one of the following 4 treatment groups:

• PBI-4050 400 mg
• PBI-4050 800 mg
• PBI-4050 1200 mg
• Placebo

All subjects will receive the assigned study drug for 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Barrie, Canada
    • LMC Clinical Research Inc.
  • Calgary, Canada
    • C-health - C-endo Division
  • Laval, Canada
    • Centre de Recherche Clinique de Laval
  • Montréal, Canada
    • Institut de recherches cliniques de Montréal (IRCM)
  • Montréal, Canada
    • LMC Clinical Research Inc.
  • Quebec City, Canada
    • Manna Research
  • Sherwood Park, Canada
    • Synergy Medical Clinic
  • Toronto, Canada
    • Manna Research
  • Vancouver, Canada
    • Manna Research
  • Alberta
    • Edmonton, Alberta, Canada
      • C-health
  • Quebec
    • Mirabel, Quebec, Canada
      • Omnispec Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is 18 years of age or older.
2. Subject has signed written informed consent.
3. Subject has a clinical diagnosis of T2DM with an HbA1c level between ≥ 7.5% and ≤ 10%.
4. Subject has been receiving stable antidiabetic therapy (with or without basal insulin) for a minimum of 3 months before the screening visit.
5. Subject is able and willing to self-monitor blood glucose level at home.
6. Subject has a body mass index (BMI) of ≥ 27 kg/m2 and ≤ 45 kg/m2.
7. Subject has metabolic syndrome, having at least 3 of the 5 risk factors.

Exclusion Criteria:

1. Subject is using prandial insulin or pre-mixed insulin in addition to oral hypoglycaemic agents for blood glucose control.
2. Subject is taking basal insulin dose > 1.0 U/kg/day.
3. Subject has recent or on-going infection requiring systemic treatment with an anti-infective agent within 30 days before screening.
4. Subject has a history of pancreatitis or diabetic ketoacidosis.
5. Subject has had at least one episode of severe hypoglycaemia in the past 12 months.
6. Subject has evidence of significant cardiovascular disease within 3 months before screening.
7. Subject has an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.
8. Subject has uncontrolled hypertension.
9. Subject has a diagnosis of rheumatic or inflammatory disease; or other autoimmune or inflammatory disease.
10. Subject is concurrently taking and plans to routinely continue taking anti-inflammatory medications during the study.
11. Subject is currently using medications for the indication of (or at the doses indicated for) weight loss.
12. Subject has significantly elevated liver enzyme levels.
13. History of malignancy of any organ system, treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
14. Subject has a history of chronic alcohol or other substance abuse.
15. Subject has a history of an allergic reaction to PBI-4050 or any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Daily dose of 6 capsules of placebo	Other: Placebo; Placebo soft gelatine capsule
ACTIVE_COMPARATOR: PBI-4050 400 mg; Daily dose of 2 capsules of PBI-4050 and 4 capsules of placebo	Other: Placebo; Placebo soft gelatine capsule; Drug: PBI-4050; Soft gelatine capsule containing 200 mg of the active ingredient per capsule
ACTIVE_COMPARATOR: PBI-4050 800 mg; Daily dose of 4 capsules of PBI-4050 and 2 capsules of placebo	Other: Placebo; Placebo soft gelatine capsule; Drug: PBI-4050; Soft gelatine capsule containing 200 mg of the active ingredient per capsule
ACTIVE_COMPARATOR: PBI-4050 1200 mg; Daily dose of 6 capsules of PBI-4050	Drug: PBI-4050; Soft gelatine capsule containing 200 mg of the active ingredient per capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of PBI-4050 400 mg, 800 mg, and 1200 mg as assessed by the number of subjects with abnormal laboratory values and/or adverse events that are related to treatment	Number of subjects with abnormal laboratory values and/or adverse events that are related to treatment	4 months
To evaluate the efficacy of PBI-4050 400 mg, 800 mg, and 1200 mg	Change from baseline on HbA1c levels	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on diabetic biomarkers	% reduction and/or increase of diabetic biomarkers such as fasting glucose, fasting insulin, fasting C-peptide	3 months
Change from baseline on pro-inflammatory/inflammatory biomarkers	% reduction and/or increase of biomarkers such as IL-6, IL-18, adiponectin	3 months
To evaluate the effect of PBI-4050 on frequency of hypoglycaemia events	Frequency of hypoglycaemia events	3 months

Collaborators and Investigators

• Sponsor: Liminal BioSciences Ltd.
• Investigators: Study Chair: John Moran, MD, ProMetic Life Sciences Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 29, 2017
• Primary Completion (ACTUAL): September 6, 2018
• Study Completion (ACTUAL): September 6, 2018

Study Registration Dates

• First Submitted: March 10, 2017
• First Submitted That Met QC Criteria: March 15, 2017
• First Posted (ACTUAL): March 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease; Insulin Resistance; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: PBI-4050-CT-9-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No