Randomized Trial Comparing Colesevelam vs. Ezetimibe

Type 2 Diabetes Mellitus Clinical Trial

— GOAL-RCT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02682680
• Other study ID #: GOAL RCT
• Status: Completed
• Phase: Phase 4
• Start date: January 11, 2016
• Est. completion date: May 25, 2017

Study information

• Verified date: November 2019
• Source: LMC Diabetes & Endocrinology Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 25, 2017
• Est. primary completion date: May 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Colesevelam
Colesevelam 3.75 g daily for 24 weeks
• Ezetimibe
Ezetimibe 10 mg daily for 24 weeks

Locations

Country	Name	City	State
Canada	LMC Barrie	Barrie	Ontario
Canada	LMC Brampton	Brampton	Ontario
Canada	LMC Calgary	Calgary	Alberta
Canada	LMC Etobicoke	Etobicoke	Ontario
Canada	LMC Markham	Markham	Ontario
Canada	LMC Oakville	Oakville	Ontario
Canada	LMC Thornhill	Thornhill	Ontario
Canada	LMC Bayview	Toronto	Ontario
Canada	Manna Toronto	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
LMC Diabetes & Endocrinology Ltd.	Bausch Health Americas, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in body weight		24 weeks
Other	Change in body mass index (BMI)		24 weeks
Other	Change in waist circumference		24 weeks
Other	Effect of colesevelam versus ezetimibe on the increased LDL cholesterol levels typically observed with initiation of SGLT2i therapy		24 weeks
Other	Persistence of therapy of colesevelam versus ezetimibe		24 weeks
Other	Persistence of therapy of colesevelam versus ezetimibe in the sub-group of subjects on SGLT2i therapy		24 weeks
Other	Mean dose of colesevelam		12 weeks and 24 weeks
Primary	Proportion of subjects who achieve target HbA1c and LDL cholesterol	target HbA1c: = 7.0%; target LDL cholesterol: = 2.0 mmol/L	24 weeks
Secondary	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
Secondary	Absolute change in LDL cholesterol		24 weeks
Secondary	Absolute change in non-high-density lipoprotein (non-HDL) cholesterol		24 weeks
Secondary	Absolute change in fasting plasma glucose (FPG)		24 weeks
Secondary	Absolute change in HbA1c		24 weeks
Secondary	Absolute change in LDL cholesterol in sub-group of subjects on SGLT2i therapy		24 weeks
Secondary	Absolute change in non-HDL cholesterol in sub-group of subjects on SGLT2i therapy		24 weeks
Secondary	Absolute change in FPG in sub-group of subjects on SGLT2i therapy		12 weeks and 24 weeks
Secondary	Absolute change in HbA1c in sub-group of subjects on SGLT2i therapy		12 weeks and 24 weeks
Secondary	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
Secondary	Proportion of subjects achieving a composite target of glycemic control with no hypoglycemia and no weight gain		24 weeks
Secondary	Proportion of subjects with = 0.3% reduction in HbA1c and = 10% reduction in LDL cholesterol from baseline		24 weeks
Secondary	Proportion of subjects with = 0.5% reduction in HbA1c and = 15% reduction in LDL cholesterol		24 weeks
Secondary	Absolute change in high-sensitivity C-reactive protein (hs-CRP) levels from baseline		24 weeks
Secondary	Absolute change in triglyceride levels from baseline		24 weeks
Secondary	Proportion of subjects achieving target HbA1c and LDL cholesterol in the sub-group of subjects on non-insulin therapies		24 weeks
Secondary	Absolute change in FPG in the sub-group of subjects on non-insulin therapies		24 weeks
Secondary	Absolute change in HbA1c in the sub-group of subjects on non-insulin therapies		24 weeks
Secondary	Absolute change in LDL cholesterol in the sub-group of subjects on non-insulin therapies		24 weeks
Secondary	Absolute change in non-HDL cholesterol in the sub-group of subjects on non-insulin therapies		24 weeks
Secondary	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
Secondary	Absolute change in alanine aminotransferase (ALT)		24 weeks
Secondary	Absolute change in creatine kinase (CK)		24 weeks