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

Phase 2

Terminated

• Conditions: Type 2 Diabetes Mellitus; Metabolic Syndrome
• Interventions: Drug: PBI-4050; Other: Placebo

• Registration Number: NCT03081598
• Lead Sponsor: Liminal BioSciences Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-03-10
• Study First Submitted QC: 2017-03-15
• Study First Posted: 2017-03-16
• Study Start: 2017-05-29
• Primary Completion: 2018-09-06
• Study Completion: 2018-09-06
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-07
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 104

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PBI-4050 400 mg	PBI-4050	Daily dose of 2 capsules of PBI-4050 and 4 capsules of placebo
PBI-4050 400 mg	Placebo	Daily dose of 2 capsules of PBI-4050 and 4 capsules of placebo
PBI-4050 800 mg	Placebo	Daily dose of 4 capsules of PBI-4050 and 2 capsules of placebo
Placebo	Placebo	Daily dose of 6 capsules of placebo
PBI-4050 1200 mg	PBI-4050	Daily dose of 6 capsules of PBI-4050
PBI-4050 800 mg	PBI-4050	Daily dose of 4 capsules of PBI-4050 and 2 capsules of placebo

Primary Outcome Measures

Name	Time	Method
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	4 months	Number of subjects with abnormal laboratory values and/or adverse events that are related to treatment
To evaluate the efficacy of PBI-4050 400 mg, 800 mg, and 1200 mg	3 months	Change from baseline on HbA1c levels

Secondary Outcome Measures

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

Trial Locations

Locations (8)

Omnispec Clinical Research; 🇨🇦 Mirabel, Quebec, Canada

C-Health; 🇨🇦 Edmonton, Alberta, Canada

LMC Clinical Research Inc.; 🇨🇦 Montréal, Canada

Centre de recherche clinique de Laval; 🇨🇦 Laval, Canada

C-health - C-endo Division; 🇨🇦 Calgary, Canada

Institut de Recherches Cliniques de Montreal (IRCM); 🇨🇦 Montréal, Canada

Manna Research; 🇨🇦 Vancouver, Canada

Synergy Medical Clinic; 🇨🇦 Sherwood Park, Canada