Randomized Trial Comparing Colesevelam vs. Ezetimibe

Study Overview
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Brief Summary
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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
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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 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 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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Colesevelam
* Drug: Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of type 2 diabetes > 6 months HbA1c level between 7.1 to 10.0% (inclusive) within three months of study enrollment LDL cholesterol > 2.0 mmol/L within three months of study enrollment 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 Stable diabetes medications for previous three months (apart from adjustment of insulin dose) Informed consent Exclusion Criteria: 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 Triglycerides ≥ 5.0 mmol/L or incalculable LDL cholesterol 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colesevelam<br>Colesevelam 3.75 g daily (tablets or oral suspension) for 24 weeks | Drug: Colesevelam<br>* Colesevelam 3.75 g daily for 24 weeks<br>* Other names: Welchol;|
| Active Comparator: Ezetimibe<br>Ezetimibe 10 mg once daily for 24 weeks | Drug: Ezetimibe<br>* Ezetimibe 10 mg daily for 24 weeks<br>* Other names: Zetia;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, hyperlipidaemia, colesevelam, ezetimibe, LDL cholesterol, glycated hemoglobin