Bempedoic Acid + Ezetimibe Fixed-Dose Combination (FDC) Study in Patients With Type 2 Diabetes and Elevated LDL-C

Study Overview
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Brief Summary
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12 week study to assess the LDL-C lowering efficacy, other lipid and glycemic measures, and safety of bempedoic acid/ezetimibe FDC compared to ezetimibe and placebo in patients with type 2 diabetes (T2D) and elevated LDL-C

Detailed Description
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Assess efficacy of FDC vs. ezetimibe vs. placebo for 12 week LDL-C lowering, changes in atherogenic lipids, hsCRP and exploratory glycemic measures as well as safety in patients with type 2 diabetes and elevated LDL-C.

Official Title
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A Randomized Study to Evaluate the Efficacy and Safety of Bempedoic Acid 180 + Ezetimibe 10 Fixed-Dose Combination Compared to Ezetimibe and Placebo In Subjects With T2DM and Elevated LDL-Cholesterol

Conditions
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Diabetes Mellitus, Type 2, Cholesterolemia, Diabetes

Intervention / Treatment
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* Drug: Bempedoic acid + Ezetimibe FDC Oral Tablet
* Drug: Ezetimibe 10 mg Oral Tablet
* Drug: Placebo Oral Tablet
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes for 6 months or greater Currently taking stable diabetes medication for 3 months or greater HbA1c between 7-10% LDL-cholesterol greater than 70 mg/dL Women must not be pregnant, lactating, or planning to become pregnant within 30 days after last dose of study medication; and must be postmenopausal, surgically sterile, or willing to use 1 acceptable form of birth control during the study through 30 days after the last dose of study medication Exclusion Criteria: Body mass index > 40 kg/m2 History of documented clinically significant cardiovascular disease Fasting triglycerides > 400 mg/dL History of Type 1 diabetes Uncontrolled hypothyroidism, liver dysfunction, renal dysfunction, gastrointestinal condition that may affect drug absorption, hematologic or coagulation disorder or active malignancy History of drug or alcohol abuse within 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bempedoic acid + Ezetimibe FDC<br>Bempedoic acid + Ezetimibe FDC Oral Tablet; Placebo oral capsule | Drug: Bempedoic acid + Ezetimibe FDC Oral Tablet<br>* Experimental therapy of bempedoic acid 180 mg + ezetimibe 10 mg FDC tablet<br>Drug: Placebo oral capsule<br>* Placebo over-encapsulated for blinding purposes<br>|
| Active Comparator: Ezetimibe 10 mg<br>Ezetimibe 10Mg Oral Tablet; Placebo Oral Tablet | Drug: Ezetimibe 10 mg Oral Tablet<br>* Ezetimibe 10 mg tablet, overencapsulated for blinding purposes<br>* Other names: Zetia;Drug: Placebo Oral Tablet<br>* Placebo tablet, matched for the FDC product for blinding purposes<br>|
| Placebo Comparator: Placebo<br>Placebo Oral Tablet, Placebo oral capsule | Drug: Placebo Oral Tablet<br>* Placebo tablet, matched for the FDC product for blinding purposes<br>Drug: Placebo oral capsule<br>* Placebo over-encapsulated for blinding purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12/End of Study (EOS) in Low-density Lipoprotein Cholesterol (LDL-C) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at the Screening Visit 3 (Visit S3) and the Treatment Visit 1 (Visit T1) (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment as factor and Baseline lipid parameter as a covariate. Missing data for LDL-C was imputed using the last observation carried forward (LOCF) method. Percent change from Baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used. | Baseline; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12/EOS in LDL-C (Comparing Ezetimibe With Placebo) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for LDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for LDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to the first dose of investigational medicinal product (IMP). Percent change from Baseline for hsCRP was analyzed using a non-parametric approach. Percent change from Baseline was calculated as: ([hsCRP value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For hsCRP, if a measured hsCRP value was available, measured hsCRP was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the average of non-HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for non-HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for non-HDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For non-HDL-C, if a measured non-HDL-C value was available, measured non-HDL-C was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the average of TC values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for TC was imputed using the LOCF method. Percent change from Baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For TC, if a measured TC value was available, measured TC was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for apo B. Baseline was defined as the last value prior to the first dose of IMP. Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for apo B was imputed using the LOCF method. Percent change from Baseline was calculated as: ([apo B value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For apo B, if a measured apo B value was available, measured apo B was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Triglycerides (TGs) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the average of TG values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for TGs was analyzed using a non-parametric approach. Percent change from Baseline was calculated as: ([TG value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For TGs, if a measured TG value was available, measured TG was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was defined as the average of HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for HDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: ([HDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For HDL-C, if a measured HDL-C value was available, measured HDL-C was used. | Baseline; Week 12 | 
| Number of Participants With LDL-C <70 Milligrams Per Deciliter (mg/dL) at Week 12 | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used. | Week 12 | 
| Secondary Outcome Measure: Number of Participants With an LDL-C Reduction of ≥50% From Baseline at Week 12 | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. LDL-C reduction from Baseline was calculated as the LDL-C value at Week 12 minus the Baseline value. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used. | Baseline; Week 12 | 
| Change From Baseline to Week 12 in Hemoglobin A1C (HbA1c) | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HbA1c. Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1). Change from Baseline was calculated as the HbA1c value at Week 12 minus the Baseline value. For HbA1c, if a measured HbA1c value was available, measured HbA1c was used. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in HbA1c | Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HbA1c. Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1). Percent change from Baseline for HbA1C was analyzed using ANCOVA, with treatment as factor and Baseline HbA1C value as a covariate. Percent change from Baseline for HbA1c was calculated as: ([HbA1c value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For HbA1c, if a measured HbA1c value was available, measured HbA1c was used. | Baseline; Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, cholesterolemia, type 2 diabetes, LDL-C, T2D, diabetes mellitus