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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Triplet Therapy | Experimental | Bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg taken orally, daily. |
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| placebo | Placebo Comparator | Matching placebos taken orally, daily. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bempedoic acid 180mg | Drug | bempedoic acid 180 mg |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline; Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ron Haberman, MD | Esperion Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PMG Research of Christie Clinic | Champaign | Illinois | 61820 | United States | ||
| PMG Research of Cary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27892461 | Background | Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457. | |
| 27663902 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received matching oral placebo once a day. |
| FG001 | Triplet Therapy | Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 11, 2016 | Mar 12, 2020 |
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| Ezetimibe 10mg | Drug | ezetimibe 10 mg |
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| Atorvastatin 20mg | Drug | atorvastatin 20 mg |
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| Placebo | Other | placebo |
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| Baseline; Week 6 |
| 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. | Baseline; Week 6 |
| 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. | Week 6 |
| 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. | Baseline; Week 6 |
| Cary |
| North Carolina |
| 27518 |
| United States |
| PMG Research of Charlotte | Charlotte | North Carolina | 28209 | United States |
| Sensenbrenner Primary Care | Charlotte | North Carolina | 28277 | United States |
| PMG Research of Hickory | Hickory | North Carolina | 28601 | United States |
| PMG Research of Raleigh | Raleigh | North Carolina | 27609 | United States |
| PMG Research of Rocky Mount | Rocky Mount | North Carolina | 27804 | United States |
| PMG Research Salisbury | Salisbury | North Carolina | 28144 | United States |
| PMG Research of Wilmington | Wilmington | North Carolina | 28401 | United States |
| PMG Research of Charleston | Mt. Pleasant | South Carolina | 29464 | United States |
| Hampton Roads Center for Clinical Research | Virginia Beach | Virginia | 23451 | United States |
| Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4. |
| 27206943 | Background | Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6. |
| 27138185 | Background | Ballantyne CM, McKenney JM, MacDougall DE, Margulies JR, Robinson PL, Hanselman JC, Lalwani ND. Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy. Am J Cardiol. 2016 Jun 15;117(12):1928-33. doi: 10.1016/j.amjcard.2016.03.043. Epub 2016 Apr 6. |
| 26073387 | Background | Thompson PD, Rubino J, Janik MJ, MacDougall DE, McBride SJ, Margulies JR, Newton RS. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015 May-Jun;9(3):295-304. doi: 10.1016/j.jacl.2015.03.003. Epub 2015 Mar 19. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received matching oral placebo once a day. |
| BG001 | Triplet Therapy | Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values | Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). LDL-C, low-density lipoprotein cholesterol. non-HDL-C, non-high-density lipoprotein cholesterol. TC, total cholesterol. TG, triglycerides. | Mean | Standard Deviation | milligrams per deciliter (mg/dL) |
| ||||||||||||||
| Baseline Apolipoprotein B (apoB) Values | Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. | Mean | Standard Deviation | mg/dL |
| ||||||||||||||
| Baseline High-Sensitivity C-Reactive Protein (hs-CRP) Values | Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. | Median | Full Range | milligrams per Liter |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | Standard Error | percent change | Baseline; Week 6 |
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| 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. | Modified Intent-to-Treat Population. Only those participants with data available were analyzed. | Posted | Least Squares Mean | Standard Error | percent change | Baseline; Week 6 |
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| 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. | Modified Intent-to-Treat Population. Only those participants with data available were analyzed. | Posted | Median | Inter-Quartile Range | percent change | Baseline; Week 6 |
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| 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. | Modified Intent-to-Treat Population. Only those participants with data available were analyzed. | Posted | Count of Participants | Participants | Week 6 |
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| 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. | Modified Intent-to-Treat Population. Only those participants with data available were analyzed. | Posted | Count of Participants | Participants | Baseline; Week 6 |
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up to 6 weeks plus 30 days
Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received matching oral placebo once a day. | 0 | 20 | 0 | 20 | 7 | 20 |
| EG001 | Triplet Therapy | Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day. | 0 | 43 | 0 | 43 | 15 | 43 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDra 19.1 | Systematic Assessment |
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| Liver function test increased | Investigations | MedDra 19.1 | Systematic Assessment |
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| Platelet count increased | Investigations | MedDra 19.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDra 19.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDra 19.1 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDra 19.1 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDra 19.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDra 19.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDra 19.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDra 19.1 | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDra 19.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDra 19.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDra 19.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDra 19.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDra 19.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDra 19.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDra 19.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDra 19.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDra 19.1 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDra 19.1 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDra 19.1 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDra 19.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDra 19.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDra 19.1 | Systematic Assessment |
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| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 19.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDra 19.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Esperion Therapeutics, Inc. | 1-833-377-7633 | medinfo@esperion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 3, 2017 | Mar 12, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C581236 | 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid |
| D000069438 | Ezetimibe |
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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| Male |
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| Asian |
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| Black or African American |
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| White |
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| non-HDL-C |
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| HDL-C |
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| Counts |
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| Participants |
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