NCT03001076

Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C (CLEAR Tranquility)

Completed Phase 3 Results posted Last updated 11 May 2020

What this trial tests

Phase 3 trial testing Bempedoic acid in Hypercholesterolemia in 269 participants. Completed in 12 February 2018.

Timeline

29 November 2016

Primary endpoint
11 January 2018

12 February 2018

Quick facts

Lead sponsor	Esperion Therapeutics, Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	269
Start date	29 November 2016
Primary completion	11 January 2018
Estimated completion	12 February 2018
Sites	1 location across United States

Drugs / interventions tested

• Bempedoic acid (BEMPEDOIC ACID) — full drug profile →
• Ezetimibe (EZETIMIBE) — full drug profile →
• Placebo

Conditions studied

• Hypercholesterolemia — all drugs for Hypercholesterolemia →
• Atherosclerosis — all drugs for Atherosclerosis →
• Statin Adverse Reaction — all drugs for Statin Adverse Reaction →

Sponsor

Esperion Therapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with Hypercholesterolemia or Atherosclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Primary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Bempedoic Acid = BA. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment as

Group	Value	95% CI
Placebo	4.99	± 2.299
Bempedoic Acid	-23.46	± 1.945

Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for non-HDL-C. Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: (\[non-HDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline

Group	Value	95% CI
Placebo	5.19	± 2.202
Bempedoic Acid	-18.38	± 1.668

Percent Change From Baseline to Week 12 in Total Cholesterol (TC) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for TC. Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: (\[TC value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. In the ANCOV

Group	Value	95% CI
Placebo	2.88	± 1.553
Bempedoic Acid	-15.11	± 1.282

Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for apoB. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in apoB was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing apoB data at We

Group	Value	95% CI
Placebo	4.74	± 1.786
Bempedoic Acid	-14.58	± 1.497

Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for hsCRP. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100.

Group	Value	95% CI
Placebo	2.088	-32.143 – 49.224
Bempedoic Acid	-32.521	-55.556 – 10.714

Percent Change From Baseline to Week 12 in Triglycerides (TGs) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to D 1. Percent change from baseline was calculated as: \[(TGs value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.

Group	Value	95% CI
Placebo	9.23	± 4.218
Bempedoic Acid	4.70	± 3.068

Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) Secondary · Week 12

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was defined as the mean of the HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.

Group	Value	95% CI
Placebo	-1.38	± 1.389
Bempedoic Acid	-7.27	± 1.214

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · Up to approximately 16 weeks

TEAEs, defined as an adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and prior to the last dose of double-blind study drug + 30 days, were collected and reported.

TEAEs

Group	Value	95% CI
Placebo	39
Bempedoic Acid	88

Non-serious TEAEs

Group	Value	95% CI
Placebo	18
Bempedoic Acid	46

Serious TEAEs

Group	Value	95% CI
Placebo	3
Bempedoic Acid	5

Deaths

Group	Value	95% CI
Placebo	0
Bempedoic Acid	0

Percent Change From Baseline to Weeks 4 and 8 in LDL-C Secondary · Week 4 and Week 8

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(LDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate

Week 4

Group	Value	95% CI
Placebo	3.05	± 1.442
Bempedoic Acid	-28.04	± 1.704

Week 8

Group	Value	95% CI
Placebo	3.61	± 1.773
Bempedoic Acid	-25.51	± 1.773

Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C Secondary · Week 4 and Week 8

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for Non-HDL-C. Baseline was defined as the mean of the Non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(Non-HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baselin

Week 4

Group	Value	95% CI
Placebo	3.08	± 1.362
Bempedoic Acid	-22.17	± 1.457

Week 8

Group	Value	95% CI
Placebo	3.71	± 1.660
Bempedoic Acid	-20.04	± 1.531

Percent Change From Baseline to Weeks 4 and 8 in TC Secondary · Week 4 and Week 8

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(TC value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.

Week 4

Group	Value	95% CI
Placebo	2.08	± 1.000
Bempedoic Acid	-18.33	± 1.129

Week 8

Group	Value	95% CI
Placebo	1.82	± 1.110
Bempedoic Acid	-16.63	± 1.215

Percent Change From Baseline to Weeks 4 and 8 in TGs Secondary · Week 4 and Week 8

Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(TGs value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.

Week 4

Group	Value	95% CI
Placebo	6.00	± 4.273
Bempedoic Acid	5.20	± 2.536

Week 8

Group	Value	95% CI
Placebo	7.68	± 4.246
Bempedoic Acid	7.60	± 2.849

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 16 weeks. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 3/87 (3%)

Deaths: 0/87

Bempedoic Acid

Serious: 5/181 (3%)

Deaths: 0/181

Serious adverse events (11 terms)

Reaction	System	Placebo	Bempedoic Acid
Intestinal obstruction	Gastrointestinal disorders	—	—
Bronchitis	Infections and infestations	—	—
Pneumonia bacterial	Infections and infestations	—	—
Poisoning deliberate	Injury, poisoning and procedural complications	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—
Subdural haemorrhage	Injury, poisoning and procedural complications	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Syncope	Nervous system disorders	—	—
Dysuria	Renal and urinary disorders	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Placebo	Bempedoic Acid
Blood uric acid increase	Investigations	—	—
Headache	Nervous system disorders	—	—
Liver function test increased	Investigations	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Glomerular filtration rate decreased	Investigations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Vertigo	Ear and labyrinth disorders	—	—
Vulvovaginal mycotic infection	Infections and infestations	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Intestinal obstruction, Bronchitis, Pneumonia bacterial, Poisoning deliberate, Subdural haematoma, Subdural haemorrhage, Osteoarthritis, Breast cancer.

Data from ClinicalTrials.gov NCT03001076 adverse events section.

Sponsor's own description

The purpose of this study is to determine if bempedoic acid (ETC-1002) added-on to ezetimibe therapy is effective and safe versus placebo in patients with elevated LDL cholesterol.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Reprogramming of fatty acid metabolism in cancer.
   Koundouros N, Poulogiannis G. · · 2020 · cited 1177× · PMID 31819192 · DOI 10.1038/s41416-019-0650-z
2. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study.
   Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, et al · · 2018 · cited 272× · PMID 29910030 · DOI 10.1016/j.atherosclerosis.2018.06.002
3. Multifunctional nanoparticle-mediated combining therapy for human diseases.
   Li X, Peng X, Zoulikha M, Boafo GF, et al · · 2024 · cited 207× · PMID 38161204 · DOI 10.1038/s41392-023-01668-1
4. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia.
   Banach M, Duell PB, Gotto AM, Laufs U, et al · · 2020 · cited 124× · PMID 32609313 · DOI 10.1001/jamacardio.2020.2314
5. Role of Bempedoic Acid in Clinical Practice.
   Ballantyne CM, Bays H, Catapano AL, Goldberg A, et al · · 2021 · cited 97× · PMID 33818688 · DOI 10.1007/s10557-021-07147-5
6. Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis.
   Cicero AFG, Fogacci F, Hernandez AV, Banach M, et al · · 2020 · cited 71× · PMID 32673317 · DOI 10.1371/journal.pmed.1003121
7. Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: A post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials.
   Leiter LA, Banach M, Catapano AL, Duell PB, et al · · 2022 · cited 48× · PMID 34981622 · DOI 10.1111/dom.14645
8. Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome.
   Biolo G, Vinci P, Mangogna A, Landolfo M, et al · · 2022 · cited 43× · PMID 36386319 · DOI 10.3389/fcvm.2022.1028355