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

Phase 2

Completed

• Conditions: Diabetes; Diabetes Mellitus, Type 2; Cholesterolemia
• Interventions: Drug: Bempedoic acid + Ezetimibe FDC Oral Tablet; Drug: Ezetimibe 10 mg Oral Tablet; Drug: Placebo oral capsule; Drug: Placebo Oral Tablet

• Registration Number: NCT03531905
• Lead Sponsor: Esperion Therapeutics, Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-05-09
• Study First Submitted: 2018-05-09
• Study First Submitted QC: 2018-05-09
• Study First Posted: 2018-05-22
• Primary Completion: 2019-06-18
• Study Completion: 2019-06-18
• Results First Submitted: 2020-03-25
• Status Verified: 2020-04
• Results First Submitted QC: 2020-04-08
• Last Update Submitted: 2020-04-08
• Results First Posted: 2020-04-09
• Last Update Posted: 2020-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 242

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Bempedoic acid + Ezetimibe FDC	Bempedoic acid + Ezetimibe FDC Oral Tablet	Bempedoic acid + Ezetimibe FDC Oral Tablet; Placebo oral capsule
Bempedoic acid + Ezetimibe FDC	Placebo oral capsule	Bempedoic acid + Ezetimibe FDC Oral Tablet; Placebo oral capsule
Ezetimibe 10 mg	Placebo Oral Tablet	Ezetimibe 10Mg Oral Tablet; Placebo Oral Tablet
Placebo	Placebo Oral Tablet	Placebo Oral Tablet, Placebo oral capsule
Placebo	Placebo oral capsule	Placebo Oral Tablet, Placebo oral capsule
Ezetimibe 10 mg	Ezetimibe 10 mg Oral Tablet	Ezetimibe 10Mg Oral Tablet; Placebo Oral Tablet

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 12/End of Study (EOS) in Low-density Lipoprotein Cholesterol (LDL-C)	Baseline; 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 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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12/EOS in LDL-C (Comparing Ezetimibe With Placebo)	Baseline; 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. 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.
Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12 in Triglycerides (TGs)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)	Baseline; Week 12	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.
Number of Participants With LDL-C <70 Milligrams Per Deciliter (mg/dL) at Week 12	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.
Secondary Outcome Measure: Number of Participants With an LDL-C Reduction of ≥50% From Baseline at Week 12	Baseline; 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.
Change From Baseline to Week 12 in Hemoglobin A1C (HbA1c)	Baseline; Week 12	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.
Percent Change From Baseline to Week 12 in HbA1c	Baseline; Week 12	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.

Trial Locations

Locations (4)

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

FInlay Medical Research; 🇺🇸 Miami, Florida, United States

L-MARC Research Center; 🇺🇸 Louisville, Kentucky, United States

Hampton Roads Center for Clinical Research; 🇺🇸 Suffolk, Virginia, United States