Clinical trial NCT02682680: Randomized Trial Comparing Colesevelam vs. Ezetimibe
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
hyperlipidaemia
colesevelam
ezetimibe
LDL cholesterol
glycated hemoglobin
Lead sponsor: LMC Diabetes & Endocrinology Ltd.
Sponsor class: OTHER
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2016-02-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of subjects who achieve target HbA1c and LDL cholesterol
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of subjects who achieve the primary outcome measure in the sub-group of subjects on sodium/glucose cotransporter 2 inhibitor (SGLT2i) therapy
timeFrame: 24 weeks
measure: Absolute change in LDL cholesterol
timeFrame: 24 weeks
measure: Absolute change in non-high-density lipoprotein (non-HDL) cholesterol
timeFrame: 24 weeks
measure: Absolute change in fasting plasma glucose (FPG)
timeFrame: 24 weeks
measure: Absolute change in HbA1c
timeFrame: 24 weeks
measure: Absolute change in LDL cholesterol in sub-group of subjects on SGLT2i therapy
timeFrame: 24 weeks
measure: Absolute change in non-HDL cholesterol in sub-group of subjects on SGLT2i therapy
timeFrame: 24 weeks
measure: Absolute change in FPG in sub-group of subjects on SGLT2i therapy
timeFrame: 12 weeks and 24 weeks
measure: Absolute change in HbA1c in sub-group of subjects on SGLT2i therapy
timeFrame: 12 weeks and 24 weeks
measure: Proportion of subjects achieving a composite target of glycemic control, LDL cholesterol control and blood pressure control
timeFrame: 24 weeks
measure: Proportion of subjects achieving a composite target of glycemic control with no hypoglycemia and no weight gain
timeFrame: 24 weeks
measure: Proportion of subjects with ≥ 0.3% reduction in HbA1c and ≥ 10% reduction in LDL cholesterol from baseline
timeFrame: 24 weeks
measure: Proportion of subjects with ≥ 0.5% reduction in HbA1c and ≥ 15% reduction in LDL cholesterol
timeFrame: 24 weeks
measure: Absolute change in high-sensitivity C-reactive protein (hs-CRP) levels from baseline
timeFrame: 24 weeks
measure: Absolute change in triglyceride levels from baseline
timeFrame: 24 weeks
measure: Proportion of subjects achieving target HbA1c and LDL cholesterol in the sub-group of subjects on non-insulin therapies
timeFrame: 24 weeks
measure: Absolute change in FPG in the sub-group of subjects on non-insulin therapies
timeFrame: 24 weeks
measure: Absolute change in HbA1c in the sub-group of subjects on non-insulin therapies
timeFrame: 24 weeks
measure: Absolute change in LDL cholesterol in the sub-group of subjects on non-insulin therapies
timeFrame: 24 weeks
measure: Absolute change in non-HDL cholesterol in the sub-group of subjects on non-insulin therapies
timeFrame: 24 weeks
measure: Rate of non-severe and severe hypoglycemia
timeFrame: 24 weeks
measure: Absolute change in alanine aminotransferase (ALT)
timeFrame: 24 weeks
measure: Absolute change in creatine kinase (CK)
timeFrame: 24 weeks
Other outcomes:
measure: Change in body weight
timeFrame: 24 weeks
measure: Change in body mass index (BMI)
timeFrame: 24 weeks
measure: Change in waist circumference
timeFrame: 24 weeks
measure: Effect of colesevelam versus ezetimibe on the increased LDL cholesterol levels typically observed with initiation of SGLT2i therapy
timeFrame: 24 weeks
measure: Persistence of therapy of colesevelam versus ezetimibe
timeFrame: 24 weeks
measure: Persistence of therapy of colesevelam versus ezetimibe in the sub-group of subjects on SGLT2i therapy
timeFrame: 24 weeks
measure: Mean dose of colesevelam
timeFrame: 12 weeks and 24 weeks
Locations:
city: Calgary
country: Canada
facility: LMC Calgary
state: Alberta
city: Barrie
country: Canada
facility: LMC Barrie
state: Ontario
city: Brampton
country: Canada
facility: LMC Brampton
state: Ontario
city: Etobicoke
country: Canada
facility: LMC Etobicoke
state: Ontario
city: Markham
country: Canada
facility: LMC Markham
state: Ontario
city: Oakville
country: Canada
facility: LMC Oakville
state: Ontario
city: Thornhill
country: Canada
facility: LMC Thornhill
state: Ontario
city: Toronto
country: Canada
facility: Manna Toronto
state: Ontario
city: Toronto
country: Canada
facility: LMC Bayview
state: Ontario
Study officials:
affiliation: LMC Diabetes & Endocrinology
name: Harpreet Bajaj, MD
role: PRINCIPAL_INVESTIGATOR
References: