Randomized Trial Comparing Colesevelam vs. Ezetimibe

Goal Achievement of A1c and LDL in a Randomized Trial Comparing Colesevelam vs. Ezetimibe as Add-on to Baseline Statin Therapy: The GOAL-RCT Trial

Sponsors

Lead Sponsor: LMC Diabetes & Endocrinology Ltd.

Collaborator: Bausch Health Americas, Inc.

Source LMC Diabetes & Endocrinology Ltd.
Brief Summary

A 24-week, randomized, open-label study investigating the efficacy, safety and tolerability of colesevelam 3.75 g daily compared to ezetimibe 10 mg daily, as an add-on to baseline statin therapy in patients with type 2 diabetes mellitus (T2DM) who are not at target for glycated hemoglobin (HbA1c) (> 7.0%) and low-density lipoprotein (LDL) cholesterol (> 2.0 mmol/L).

Detailed Description

This study will enroll 200 adult patients with T2DM who are not at target for HbA1c and LDL cholesterol. Patients who are on baseline statin therapy will be randomly assigned in a 1:1 ratio to colesevelam 3.75 g daily for 24 weeks, or ezetimibe 10 mg daily for 24 weeks. If a patient has statin intolerance, they may be on a fibrate and/or niacin, or on no lipid lowering therapy. The primary efficacy objectives are

1. to demonstrate that colesevelam 3.75 g daily is non-inferior to ezetimibe 10 mg daily as add-on to statin therapy for patients achieving a composite target of HbA1c (≤ 7.0%) and LDL cholesterol (≤ 2.0 mmol/L) at week 24, and

2. to compare the proportion of patients achieving a composite target of HbA1c (≤ 7.0%) and LDL cholesterol (≤ 2.0 mmol/L) at week 24.

This study will also assess the primary composite outcome in a sub-group of patients on sodium/glucose cotransporter 2 inhibitor (SGLT2i) therapy.

Overall Status Completed
Start Date January 11, 2016
Completion Date May 25, 2017
Primary Completion Date May 25, 2017
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of subjects who achieve target HbA1c and LDL cholesterol 24 weeks
Secondary Outcome
Measure Time Frame
Proportion of subjects who achieve the primary outcome measure in the sub-group of subjects on sodium/glucose cotransporter 2 inhibitor (SGLT2i) therapy 24 weeks
Absolute change in LDL cholesterol 24 weeks
Absolute change in non-high-density lipoprotein (non-HDL) cholesterol 24 weeks
Absolute change in fasting plasma glucose (FPG) 24 weeks
Absolute change in HbA1c 24 weeks
Absolute change in LDL cholesterol in sub-group of subjects on SGLT2i therapy 24 weeks
Absolute change in non-HDL cholesterol in sub-group of subjects on SGLT2i therapy 24 weeks
Absolute change in FPG in sub-group of subjects on SGLT2i therapy 12 weeks and 24 weeks
Absolute change in HbA1c in sub-group of subjects on SGLT2i therapy 12 weeks and 24 weeks
Proportion of subjects achieving a composite target of glycemic control, LDL cholesterol control and blood pressure control 24 weeks
Proportion of subjects achieving a composite target of glycemic control with no hypoglycemia and no weight gain 24 weeks
Proportion of subjects with ≥ 0.3% reduction in HbA1c and ≥ 10% reduction in LDL cholesterol from baseline 24 weeks
Proportion of subjects with ≥ 0.5% reduction in HbA1c and ≥ 15% reduction in LDL cholesterol 24 weeks
Absolute change in high-sensitivity C-reactive protein (hs-CRP) levels from baseline 24 weeks
Absolute change in triglyceride levels from baseline 24 weeks
Proportion of subjects achieving target HbA1c and LDL cholesterol in the sub-group of subjects on non-insulin therapies 24 weeks
Absolute change in FPG in the sub-group of subjects on non-insulin therapies 24 weeks
Absolute change in HbA1c in the sub-group of subjects on non-insulin therapies 24 weeks
Absolute change in LDL cholesterol in the sub-group of subjects on non-insulin therapies 24 weeks
Absolute change in non-HDL cholesterol in the sub-group of subjects on non-insulin therapies 24 weeks
Rate of non-severe and severe hypoglycemia 24 weeks
Absolute change in alanine aminotransferase (ALT) 24 weeks
Absolute change in creatine kinase (CK) 24 weeks
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: Colesevelam

Description: Colesevelam 3.75 g daily for 24 weeks

Arm Group Label: Colesevelam

Intervention Type: Drug

Intervention Name: Ezetimibe

Description: Ezetimibe 10 mg daily for 24 weeks

Arm Group Label: Ezetimibe

Eligibility

Criteria:

Inclusion Criteria:

1. Diagnosis of type 2 diabetes > 6 months

2. HbA1c level between 7.1 to 10.0% (inclusive) within three months of study enrollment

3. LDL cholesterol > 2.0 mmol/L within three months of study enrollment

4. Receiving a stable dose of statin for a minimum of three months, which the investigator does not plan to change over the 24-week trial period. If patient has documented statin intolerance, may be on a fibrate and/or niacin, or on no lipid lowering therapy

5. Stable diabetes medications for previous three months (apart from adjustment of insulin dose)

6. Informed consent

Exclusion Criteria:

1. Use of a second lipid lowering therapy other than statin within three months of study enrolment, unless on a fibrate and/or niacin if patient has statin intolerance

2. Triglycerides ≥ 5.0 mmol/L or incalculable LDL cholesterol

3. Significant liver enzyme or CK elevation defined as CK or ALT ≥ 3x upper limit of normal (ULN)

5) Pregnant or breast feeding or planning to become pregnant or breast feed during the study 6) Chronic kidney disease (CKD) stage ≥4 or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m-squared 7) Severe gastroparesis or history of significant bowel resection 8) Current use of any Investigational Product

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Harpreet Bajaj, MD Principal Investigator LMC Diabetes & Endocrinology
Location
Facility:
LMC Calgary | Calgary, Alberta, Canada
LMC Barrie | Barrie, Ontario, Canada
LMC Brampton | Brampton, Ontario, L6S 0C9, Canada
LMC Etobicoke | Etobicoke, Ontario, Canada
LMC Markham | Markham, Ontario, Canada
LMC Oakville | Oakville, Ontario, Canada
LMC Thornhill | Thornhill, Ontario, Canada
Manna Toronto | Toronto, Ontario, M9W 4L6, Canada
LMC Bayview | Toronto, Ontario, Canada
Location Countries

Canada

Verification Date

November 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: LMC Diabetes & Endocrinology Ltd.

Investigator Full Name: Dr. Harpreet Bajaj

Investigator Title: Endocrinologist

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Colesevelam

Type: Experimental

Description: Colesevelam 3.75 g daily (tablets or oral suspension) for 24 weeks

Label: Ezetimibe

Type: Active Comparator

Description: Ezetimibe 10 mg once daily for 24 weeks

Acronym GOAL-RCT
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov