Randomized Trial Comparing Colesevelam vs. Ezetimibe (GOAL-RCT)

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Colesevelam; Drug: Ezetimibe

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • LMC Calgary
  • Ontario
    • Barrie, Ontario, Canada
      • LMC Barrie
    • Brampton, Ontario, Canada, L6S 0C9
      • LMC Brampton
    • Etobicoke, Ontario, Canada
      • LMC Etobicoke
    • Markham, Ontario, Canada
      • LMC Markham
    • Oakville, Ontario, Canada
      • LMC Oakville
    • Thornhill, Ontario, Canada
      • LMC Thornhill
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Toronto
    • Toronto, Ontario, Canada
      • LMC Bayview

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. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colesevelam; Colesevelam 3.75 g daily (tablets or oral suspension) for 24 weeks	Drug: Colesevelam; Colesevelam 3.75 g daily for 24 weeks; Other Names: Welchol; Lodalis
Active Comparator: Ezetimibe; Ezetimibe 10 mg once daily for 24 weeks	Drug: Ezetimibe; Ezetimibe 10 mg daily for 24 weeks; Other Names: Zetia; Ezetrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects who achieve target HbA1c and LDL cholesterol	target HbA1c: ≤ 7.0%; target LDL cholesterol: ≤ 2.0 mmol/L	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	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	glycemic control: A1c ≤ 7.0%; LDL cholesterol control: ≤ 2.0 mmol/L; blood pressure control: ≤ 130/80 mm Hg	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	Severe hypoglycemia is defined as hypoglycemia requiring third party intervention of another person to actively administer carbohydrate, glucagon or other resuscitative actions.	24 weeks
Absolute change in alanine aminotransferase (ALT)		24 weeks
Absolute change in creatine kinase (CK)		24 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change in body weight	24 weeks
Change in body mass index (BMI)	24 weeks
Change in waist circumference	24 weeks
Effect of colesevelam versus ezetimibe on the increased LDL cholesterol levels typically observed with initiation of SGLT2i therapy	24 weeks
Persistence of therapy of colesevelam versus ezetimibe	24 weeks
Persistence of therapy of colesevelam versus ezetimibe in the sub-group of subjects on SGLT2i therapy	24 weeks
Mean dose of colesevelam	12 weeks and 24 weeks

Collaborators and Investigators

• Sponsor: LMC Diabetes & Endocrinology Ltd.
• Collaborators: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Harpreet Bajaj, MD, LMC Diabetes & Endocrinology

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2016
• Primary Completion (Actual): May 25, 2017
• Study Completion (Actual): May 25, 2017

Study Registration Dates

• First Submitted: February 8, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimate): February 15, 2016

Study Record Updates

• Last Update Posted (Actual): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 22, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: diabetes; LDL cholesterol; glycated hemoglobin; ezetimibe; colesevelam; hyperlipidaemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride; Ezetimibe
• Other Study ID Numbers: GOAL RCT

Plan for Individual participant data (IPD)

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