Hypercholesterolemia
Conditions
Keywords
hyperlididemia, LDL, cholesterol
Brief summary
The purpose of this study is to determine if triplet therapy with bempedoic acid (ETC-1002) 180mg, ezetimibe 10mg, and atorvastatin 20mg is effective and safe versus placebo in patients with elevated LDL cholesterol.
Interventions
bempedoic acid 180 mg
DRUGEzetimibe 10mg
ezetimibe 10 mg
DRUGAtorvastatin 20mg
atorvastatin 20 mg
OTHERPlacebo
placebo
Sponsors
Esperion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fasting LDL-cholesterol between 130 - 189 mg/dL at screening following washout of all LDL-C-lowering drugs and nutritional supplements * Men and nonpregnant, nonlactating women * Sufficiently stable and suitable to undergo washout of all LDL-C-lowering drugs and nutritional supplements for 12 weeks
Exclusion criteria
* Fasting blood triglycerides greater than or equal to 400 mg/dL * Body Mass Index (BMI) greater than 50 kg/m2 * History of clinically significant cardiovascular disease * History of type 1 or type 2 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6 | Baseline; Week 6 | Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Percent change from Baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing LDL-C values were imputed using last observation carried forward (LOCF), with only post-Baseline values carried forward. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lipid Profile Parameters at Week 6 | Baseline; Week 6 | Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Baseline apolipoprotein B (apoB) was measured only at predose/Day 1. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing values were imputed using LOCF, with only post-Baseline values carried forward. non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol. |
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6 | Baseline; Week 6 | Percent change is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. If only one value is available either at Week -1 (Screening Visit 2) or Week 0 (Treatment Visit 1), then that value is used as Baseline. Missing values were imputed using LOCF, with only post-Baseline values carried forward. |
| Number of Participants With LDL-C <70 mg/dL at Week 6 | Week 6 | Analysis was based on LOCF values. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis. |
| Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6 | Baseline; Week 6 | If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching oral placebo once a day. | 20 |
| Triplet Therapy Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day. | 43 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Triplet Therapy | Total |
|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 7.77 | 61.2 years STANDARD_DEVIATION 12.26 | 61.2 years STANDARD_DEVIATION 10.97 |
| Baseline Apolipoprotein B (apoB) Values | 119.2 mg/dL STANDARD_DEVIATION 15.25 | 118.0 mg/dL STANDARD_DEVIATION 19.89 | 118.4 mg/dL STANDARD_DEVIATION 18.42 |
| Baseline High-Sensitivity C-Reactive Protein (hs-CRP) Values | 1.64 milligrams per Liter | 1.94 milligrams per Liter | 1.88 milligrams per Liter |
| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values HDL-C | 52.03 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.977 | 52.05 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.936 | 52.04 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.844 |
| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values LDL-C | 155.90 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 13.749 | 154.29 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 17.913 | 154.80 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 16.609 |
| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values non-HDL-C | 183.13 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 18.363 | 183.59 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 27.347 | 183.44 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.698 |
| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values TC | 235.13 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 21.196 | 235.67 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.992 | 235.50 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 25.125 |
| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values TG | 139.53 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 62.475 | 150.70 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 81.375 | 147.15 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 75.56 |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 7 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 34 Participants | 50 Participants |
| Sex: Female, Male Female | 14 Participants | 26 Participants | 40 Participants |
| Sex: Female, Male Male | 6 Participants | 17 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 43 |
| other Total, other adverse events | 7 / 20 | 15 / 43 |
| serious Total, serious adverse events | 0 / 20 | 0 / 43 |
Outcome results
Primary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6
Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Percent change from Baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing LDL-C values were imputed using last observation carried forward (LOCF), with only post-Baseline values carried forward. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.
Time frame: Baseline; Week 6
Population: Modified Intent-to-Treat Population: all randomized participants who received at least 1 dose of investigational medicinal product (IMP) and who had a Baseline assessment and at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of IMP. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6 | -3.1 percent change | Standard Error 3.27 |
| Triplet Therapy | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6 | -63.6 percent change | Standard Error 1.67 |
p-value: <0.00195% CI: [-68, -53]ANCOVA
Secondary
Number of Participants With LDL-C <70 mg/dL at Week 6
Analysis was based on LOCF values. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.
Time frame: Week 6
Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With LDL-C <70 mg/dL at Week 6 | 0 Participants |
| Triplet Therapy | Number of Participants With LDL-C <70 mg/dL at Week 6 | 37 Participants |
p-value: <0.001Fisher Exact
Secondary
Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6
If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.
Time frame: Baseline; Week 6
Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6 | 0 Participants |
| Triplet Therapy | Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6 | 39 Participants |
p-value: <0.001Fisher Exact
Secondary
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6
Percent change is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. If only one value is available either at Week -1 (Screening Visit 2) or Week 0 (Treatment Visit 1), then that value is used as Baseline. Missing values were imputed using LOCF, with only post-Baseline values carried forward.
Time frame: Baseline; Week 6
Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6 | -2.7 percent change |
| Triplet Therapy | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6 | -47.7 percent change |
p-value: <0.00195% CI: [-60, -21.4]Wilcoxon rank sum test
Secondary
Percent Change From Baseline in Lipid Profile Parameters at Week 6
Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Baseline apolipoprotein B (apoB) was measured only at predose/Day 1. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing values were imputed using LOCF, with only post-Baseline values carried forward. non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol.
Time frame: Baseline; Week 6
Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | non-HDL-C | -1.3 percent change | Standard Error 2.56 |
| Placebo | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | TG | 8.9 percent change | Standard Error 5.95 |
| Placebo | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | TC | -1.1 percent change | Standard Error 2.24 |
| Placebo | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | HDL-C | 0.4 percent change | Standard Error 2.26 |
| Placebo | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | apoB | 0.6 percent change | Standard Error 2.24 |
| Triplet Therapy | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | HDL-C | -1.1 percent change | Standard Error 1.47 |
| Triplet Therapy | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | TC | -47.1 percent change | Standard Error 1.63 |
| Triplet Therapy | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | apoB | -53.5 percent change | Standard Error 1.57 |
| Triplet Therapy | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | TG | -27.4 percent change | Standard Error 2.79 |
| Triplet Therapy | Percent Change From Baseline in Lipid Profile Parameters at Week 6 | non-HDL-C | -60.0 percent change | Standard Error 1.6 |
Comparison: non-HDL-Cp-value: <0.00195% CI: [-64.9, -52.6]ANCOVA
Comparison: TCp-value: <0.00195% CI: [-51.6, -40.4]ANCOVA
Comparison: apoBp-value: <0.00195% CI: [-59.7, -48.6]ANCOVA
Comparison: TGp-value: <0.00195% CI: [-49.7, -22.8]ANCOVA
Comparison: HDL-Cp-value: =0.58895% CI: [-7, 4]ANCOVA