Trial Outcomes & Findings for Bempedoic Acid + Ezetimibe Fixed-Dose Combination (FDC) Study in Patients With Type 2 Diabetes and Elevated LDL-C (NCT NCT03531905)

NCT ID: NCT03531905

Last Updated: 2020-04-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 242 participants
• Primary outcome timeframe: Baseline; Week 12
• Results posted on: 2020-04-09

Participant Flow

Participant milestones

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Overall Study STARTED	81	81	80
Overall Study COMPLETED	74	76	77
Overall Study NOT COMPLETED	7	5	3

Reasons for withdrawal

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Overall Study Withdrawal by Subject	3	3	2
Overall Study Lost to Follow-up	2	2	1
Overall Study Participant was out of town	1	0	0
Overall Study Could not speak with the participant	1	0	0

Baseline Characteristics

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at 3 study sites

Baseline characteristics by cohort

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=81 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=81 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=80 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.	Total n=242 Participants Total of all reporting groups
Age, Continuous	61.3 years STANDARD_DEVIATION 8.65 • n=81 Participants	61.0 years STANDARD_DEVIATION 8.00 • n=81 Participants	62.1 years STANDARD_DEVIATION 8.63 • n=80 Participants	61.4 years STANDARD_DEVIATION 8.41 • n=242 Participants
Sex: Female, Male Female	36 Participants n=81 Participants	39 Participants n=81 Participants	42 Participants n=80 Participants	117 Participants n=242 Participants
Sex: Female, Male Male	45 Participants n=81 Participants	42 Participants n=81 Participants	38 Participants n=80 Participants	125 Participants n=242 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=81 Participants	38 Participants n=81 Participants	30 Participants n=80 Participants	100 Participants n=242 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=81 Participants	43 Participants n=81 Participants	50 Participants n=80 Participants	142 Participants n=242 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=81 Participants	0 Participants n=81 Participants	0 Participants n=80 Participants	0 Participants n=242 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=81 Participants	0 Participants n=81 Participants	0 Participants n=80 Participants	2 Participants n=242 Participants
Race (NIH/OMB) Asian	3 Participants n=81 Participants	0 Participants n=81 Participants	2 Participants n=80 Participants	5 Participants n=242 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=81 Participants	0 Participants n=81 Participants	0 Participants n=80 Participants	0 Participants n=242 Participants
Race (NIH/OMB) Black or African American	15 Participants n=81 Participants	15 Participants n=81 Participants	16 Participants n=80 Participants	46 Participants n=242 Participants
Race (NIH/OMB) White	61 Participants n=81 Participants	65 Participants n=81 Participants	62 Participants n=80 Participants	188 Participants n=242 Participants
Race (NIH/OMB) More than one race	0 Participants n=81 Participants	0 Participants n=81 Participants	0 Participants n=80 Participants	0 Participants n=242 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=81 Participants	1 Participants n=81 Participants	0 Participants n=80 Participants	1 Participants n=242 Participants
Low-density lipoprotein cholesterol (LDL-C)	145.06 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 31.504 • n=60 Participants • Efficacy Analysis Set: all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at 3 study sites	139.24 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 28.121 • n=60 Participants • Efficacy Analysis Set: all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at 3 study sites	143.36 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.421 • n=59 Participants • Efficacy Analysis Set: all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at 3 study sites	142.55 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 28.715 • n=179 Participants • Efficacy Analysis Set: all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at 3 study sites
High-sensitivity C-reactive protein (hsCRP)	2.570 milligrams per liter (mg/ L) n=60 Participants • Efficacy Analysis Set	2.420 milligrams per liter (mg/ L) n=60 Participants • Efficacy Analysis Set	3.480 milligrams per liter (mg/ L) n=59 Participants • Efficacy Analysis Set	2.610 milligrams per liter (mg/ L) n=179 Participants • Efficacy Analysis Set
Non-high-density lipoprotein cholesterol (non-HDL-C)	181.69 mg/dL STANDARD_DEVIATION 36.659 • n=60 Participants • Efficacy Analysis Set	172.87 mg/dL STANDARD_DEVIATION 33.277 • n=60 Participants • Efficacy Analysis Set	177.38 mg/dL STANDARD_DEVIATION 29.116 • n=59 Participants • Efficacy Analysis Set	177.31 mg/dL STANDARD_DEVIATION 33.194 • n=179 Participants • Efficacy Analysis Set
Total cholesterol (TC)	230.34 mg/dL STANDARD_DEVIATION 37.234 • n=60 Participants • Efficacy Analysis Set	221.33 mg/dL STANDARD_DEVIATION 33.592 • n=60 Participants • Efficacy Analysis Set	225.94 mg/dL STANDARD_DEVIATION 32.830 • n=59 Participants • Efficacy Analysis Set	225.87 mg/dL STANDARD_DEVIATION 34.619 • n=179 Participants • Efficacy Analysis Set
Apolipoprotein B (Apo B)	121.6 mg/dL STANDARD_DEVIATION 22.95 • n=60 Participants • Efficacy Analysis Set	117.3 mg/dL STANDARD_DEVIATION 22.96 • n=60 Participants • Efficacy Analysis Set	120.8 mg/dL STANDARD_DEVIATION 18.53 • n=59 Participants • Efficacy Analysis Set	119.9 mg/dL STANDARD_DEVIATION 21.56 • n=179 Participants • Efficacy Analysis Set
Triglycerides (TGs)	172.25 mg/dL n=60 Participants • Efficacy Analysis Set	159.25 mg/dL n=60 Participants • Efficacy Analysis Set	163.00 mg/dL n=59 Participants • Efficacy Analysis Set	163.00 mg/dL n=179 Participants • Efficacy Analysis Set
High-density lipoprotein cholesterol (HDL-C)	48.73 mg/dL STANDARD_DEVIATION 13.067 • n=60 Participants • Efficacy Analysis Set	47.95 mg/dL STANDARD_DEVIATION 10.847 • n=60 Participants • Efficacy Analysis Set	48.53 mg/dL STANDARD_DEVIATION 13.482 • n=59 Participants • Efficacy Analysis Set	48.40 mg/dL STANDARD_DEVIATION 12.447 • n=179 Participants • Efficacy Analysis Set
Hemoglobin A1C (HbA1c)	7.86 Percent STANDARD_DEVIATION 0.927 • n=60 Participants • Efficacy Analysis Set	7.96 Percent STANDARD_DEVIATION 1.279 • n=60 Participants • Efficacy Analysis Set	8.02 Percent STANDARD_DEVIATION 0.773 • n=59 Participants • Efficacy Analysis Set	7.95 Percent STANDARD_DEVIATION 1.013 • n=179 Participants • Efficacy Analysis Set
Fasting plasma glucose	162.4 mg/dL STANDARD_DEVIATION 46.10 • n=58 Participants • Efficacy Analysis Set	153.3 mg/dL STANDARD_DEVIATION 46.73 • n=58 Participants • Efficacy Analysis Set	174.2 mg/dL STANDARD_DEVIATION 57.53 • n=57 Participants • Efficacy Analysis Set	163.2 mg/dL STANDARD_DEVIATION 50.78 • n=173 Participants • Efficacy Analysis Set
HOMA-IR index	6.709 units on a scale STANDARD_DEVIATION 6.200 • n=57 Participants • Efficacy Analysis Set	10.847 units on a scale STANDARD_DEVIATION 18.074 • n=56 Participants • Efficacy Analysis Set	13.267 units on a scale STANDARD_DEVIATION 21.305 • n=53 Participants • Efficacy Analysis Set	10.199 units on a scale STANDARD_DEVIATION 16.503 • n=166 Participants • Efficacy Analysis Set

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: Efficacy Analysis Set (EAS): all randomized participants who received at least one dose of investigational medicinal product (Full Analysis Set), excluding participants at three study sites. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=59 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12/End of Study (EOS) in Low-density Lipoprotein Cholesterol (LDL-C)	-38.8 Percent change Standard Error 2.24	-19.2 Percent change Standard Error 2.16	0.9 Percent change Standard Error 2.20

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=59 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=57 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12/EOS in LDL-C (Comparing Ezetimibe With Placebo)	-19.2 Percent change Standard Error 2.16	0.9 Percent change Standard Error 2.20	—

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)	-25.347 Percent change Interval -48.98 to 3.292	2.078 Percent change Interval -22.61 to 48.77	14.085 Percent change Interval -21.642 to 50.776

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=59 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	-33.0 Percent change Standard Error 2.01	-17.8 Percent change Standard Error 1.94	0.1 Percent change Standard Error 1.97

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=59 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	-27.3 Percent change Standard Error 1.61	-13.9 Percent change Standard Error 1.55	-0.1 Percent change Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=59 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)	-27.5 Percent change Standard Error 1.94	-14.8 Percent change Standard Error 1.88	-0.3 Percent change Standard Error 1.91

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Triglycerides (TGs)	-9.20 Percent change Interval -27.97 to 19.39	-13.59 Percent change Interval -28.58 to 1.33	-5.11 Percent change Interval -19.84 to 12.15

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=59 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)	-5.1 Percent change Standard Error 1.53	2.1 Percent change Standard Error 1.48	0.8 Percent change Standard Error 1.50

SECONDARY outcome

Timeframe: Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Number of Participants With LDL-C <70 Milligrams Per Deciliter (mg/dL) at Week 12	21 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Secondary Outcome Measure: Number of Participants With an LDL-C Reduction of ≥50% From Baseline at Week 12	22 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Change From Baseline to Week 12 in Hemoglobin A1C (HbA1c)	0.01 mg/dL Standard Deviation 0.849	-0.06 mg/dL Standard Deviation 0.851	0.03 mg/dL Standard Deviation 0.667

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=54 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=56 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=57 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in HbA1c	0.1 Percent change Standard Error 1.31	-0.7 Percent change Standard Error 1.28	0.4 Percent change Standard Error 1.27

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=53 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=55 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=55 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Fasting Plasma Glucose	4.2 Percent change Standard Error 3.29	3.7 Percent change Standard Error 3.28	1.7 Percent change Standard Error 3.27

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=55 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=53 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=50 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in 2-hour Post Prandial Plasma Glucose (PPG)	1.9 Percent change Standard Deviation 24.25	0.2 Percent change Standard Deviation 31.88	2.2 Percent change Standard Deviation 25.39

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline; Week 12

Population: EAS. Only participants with available data were analyzed.

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=51 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=53 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=55 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Index	3.0 Percent change Standard Error 9.85	2.5 Percent change Standard Error 9.59	18.9 Percent change Standard Error 9.79

OTHER_PRE_SPECIFIED outcome

Timeframe: up to approximately 16 weeks

Population: Safety Analysis Set: all randomized participants who received at least one dose of IMP

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.

Outcome measures

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=81 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=81 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=80 Participants Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	55 Participants	45 Participants	46 Participants

Adverse Events

Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Ezetimibe 10 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=81 participants at risk Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=81 participants at risk Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=80 participants at risk Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	0.00% 0/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	1.2% 1/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).
Gastrointestinal disorders Duodenal ulcer	0.00% 0/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	1.2% 1/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	0.00% 0/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).

Other adverse events

Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=81 participants at risk Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Ezetimibe 10 mg n=81 participants at risk Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=80 participants at risk Participants received placebo to match the FDC 180 mg/10 mg tablet or the ezetimibe 10 mg overencapsulated tablet, taken orally, once daily for 12 weeks.
Infections and infestations Bronchitis	0.00% 0/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	3.7% 3/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	0.00% 0/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).
Infections and infestations Urinary tract infection	3.7% 3/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	3.7% 3/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	3.8% 3/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).
Investigations Blood glucose increased	3.7% 3/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	0.00% 0/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	0.00% 0/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).
Investigations Glycosylated haemoglobin increased	2.5% 2/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	1.2% 1/81 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).	5.0% 4/80 • up to approximately 16 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind investigational medicinal product (IMP) through 30 days after the last dose of double-blind IMP, were collected in members of the Safety Population (all randomized participants who received at least 1 dose of blinded IMP).

Additional Information

Medical Director

Esperion Therapeutics, Inc.

Phone: 1-833-377-7633

Email: medinfo@esperion.com

Results disclosure agreements

• Principal investigator is a sponsor employee If the Principal Investigator plans to publish information from the study, a copy of the manuscript should be provided to the Sponsor for review before submission for publication or presentation. The Sponsor may request that that publication be withheld.
• Publication restrictions are in place

Restriction type: OTHER