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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03531905
• Other study ID #: 1002FDC-058
• Status: Completed
• Phase: Phase 2
• Start date: May 9, 2018
• Est. completion date: June 18, 2019

Study information

• Verified date: April 2020
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: June 18, 2019
• Est. primary completion date: June 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholesterolemia
• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Bempedoic acid + Ezetimibe FDC Oral Tablet
Experimental therapy of bempedoic acid 180 mg + ezetimibe 10 mg FDC tablet
• Ezetimibe 10 mg Oral Tablet
Ezetimibe 10 mg tablet, overencapsulated for blinding purposes
• Placebo Oral Tablet
Placebo tablet, matched for the FDC product for blinding purposes
• Placebo oral capsule
Placebo over-encapsulated for blinding purposes

Locations

Country	Name	City	State
United States	Clinical Trials Research	Lincoln	California
United States	L-MARC Research Center	Louisville	Kentucky
United States	FInlay Medical Research	Miami	Florida
United States	Hampton Roads Center for Clinical Research	Suffolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gutierrez MJ, Rosenberg NL, Macdougall DE, Hanselman JC, Margulies JR, Strange P, Milad MA, McBride SJ, Newton RS. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):676-83. doi: 10.1161/ATVBAHA.113.302677. Epub 2014 Jan 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change From Baseline to Week 12 in Fasting Plasma Glucose	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for fasting plasma glucose. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for fasting plasma glucose was analyzed using ANCOVA, with treatment as factor and Baseline fasting plasma glucose as a covariate. Percent change from Baseline for fasting plasma glucose was calculated as: ([fasting plasma glucose value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For fasting plasma glucose, if a measured fasting plasma glucose value was available, measured fasting plasma glucose was used.	Baseline; Week 12
Other	Percent Change From Baseline to Week 12 in 2-hour Post Prandial Plasma Glucose (PPG)	Blood samples were drawn 2 hours ± 5 minutes after the start of the meal. Samples were collected and analyzed for PPG. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for PPG was calculated as: ([PPG value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100. For PPG, if a measured PPG value was available, measured PPG was used.	Baseline; Week 12
Other	Percent Change From Baseline to Week 12 in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Index	The HOMA-IR index was calculated from the fasting glucose and insulin values that were obtained at each clinic visit (Day 1/Visit T1, Week 4/Visit T2, and Week 12/Visit T3) during the double-blind treatment period, using the formula: (fasting glucose [millimoles per milliliter {mmol/ml}] x fasting insulin [micro International Units per milliliter {µIU/ml}]) divided by 22.5. Percent change from Baseline for HOMA-IR index was analyzed using ANCOVA, with treatment as factor and Baseline HOMA-IR index as a covariate. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for HOMA-IR index was calculated as: ([HOMA-IR index value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.	Baseline; Week 12
Other	Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind IMP through 30 days after the last dose of double-blind IMP. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, including control, and which does not necessarily have a causal relationship with treatment. An AE is: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (e.g., electrocardiogram or x-ray) that results in symptoms, a change in treatment, or discontinuation from IMP; or an adverse drug reaction.	up to approximately 16 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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	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
Secondary	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
Secondary	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