Clinical Trials
Esperion Has Extensive Development and Clinical Trial Experience in Lipid Management
To fulfill our singular vision for lipid management, ESPERION has two
LDL-C lowering therapies in development: bempedoic acid and bempedoic acid/ezetimibe combination tablet, both designed to meet an unmet need.

ESPERION owns the exclusive worldwide rights to the franchise of products based on bempedoic acid.

The global, pivotal, Phase 3, clinical trials for both drugs concluded in 2018.1 The results from these
trials are the foundation for the New Drug Application (NDA) and Marketing Authorization Application (MAA) global regulatory submissions for an LDL-C lowering indication.

These submissions were made in the first quarter of 2019 for the US and Europe.

LDL-C=low-density lipoprotein cholesterol.
Bempedoic Acid Phase 3 Clinical Development
This global, pivotal Phase 3 program was designed to evaluate the safety, tolerability, and LDL-C lowering efficacy of bempedoic acid, and bempedoic acid/ezetimibe combination tablet. It included patients with atherosclerotic cardiovascular disease (ASCVD) or who are at a high risk for ASCVD and have hypercholesterolemia, who continue to have elevated levels of LDL-C while taking maximally-tolerated statins and ezetimibe, leaving them at high risk for cardiovascular events.1

The program included studies in approximately 4,000 patients: 4 trials for bempedoic acid and 1 for bempedoic acid/ezetimibe combination tablet.1

Cholesterol Lowering via BEmpedoic Acid, an ACL-inhibiting Regimen (CLEAR) Trials: LDL-C Lowering Indication (Total N=3,623)1
ASCVD and/or HeFH
Statin Add-On
 
CLEAR Harmony
(1002-040); N=2,230
52
weeks
safety
12
weeks
LDL-C
85% of patients using moderate-to-high intensity statins
 
CLEAR Wisdom
(1002-047); N=779
52
weeks
safety
12
weeks
LDL-C
93% of patients using moderate-to-high intensity statins
 
85% of patients using moderate-to-high intensity statins
 
93% of patients using moderate-to-high intensity statins
ASCVD and/or HeFH
Low, Very Low or No Statin Background Therapy
 
CLEAR Serenity
(1002-046); N=345
24
weeks
safety
12
weeks
LDL-C
0% of patients using moderate-to-high intensity statins;
8% on very low-dose statins
 
CLEAR Tranquility
(1002-048); N=269
12
weeks safety
LDL-C
0% of patients using moderate-to-high intensity statins;
31% on statins at/below lowest recommended dose
 
0% of patients using moderate-to-high intensity statins;
8% on very low-dose statins
 
0% of patients using moderate-to-high intensity statins;
31% on statins at/below lowest recommended dose
CHOLESTEROL LOWERING VIA BEMPEDOIC ACID/EZETIMIBE COMBINATION TABLET:
LDL-C LOWERING INDICATION (N=382)1
ASCVD and/or HeFH
Statin Add-On
 
(1002-053); N=382
12
weeks safety
LDL-C
 
37% of patients using high-intensity statins
High-intensity statins=atorvastatin 40-80mg; rosuvastatin 20-40mg

Moderate-intensity statins=atorvastatin 10-20mg; rosuvastatin 5-10mg; simvastatin 20-40mg; pravastatin 40-80mg; lovastatin 40mg; fluvastatin XL 80mg; fluvastatin 40mg; pitavastatin 2-4mg

All 5 trials were1:
Randomized • Double blind • Placebo controlled • Parallel group • Multicenter
Phase 3 Clinical Trials1
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-18.1%
(P<0.001)
BA:
-16.5%
Placebo:
+1.6%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-21.5%
(P<0.001)
BA:
-22.4%
Placebo:
+2.6%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Nasopharyngitis
(9.8% vs 11.7%)
Myalgia (6.0% vs 6.1%)
Prevalence of Serious AEs
(BA vs placebo)
12.4% vs 9.4%
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
10.9% vs 7.1%
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-17.4%
(P<0.001)
BA:
-15.1%
Placebo:
+2.4%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-8.7%
(P<0.001)
BA:
-18.7%
Placebo:
-9.4%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Nasopharyngitis
(5.2% vs 5.1%)
Urinary Tract Infection (5.0% vs 1.9%)
Prevalence of Serious AEs
(BA vs placebo)
20.3% vs 18.7%
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
10.9% vs 8.6%
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-21.4%
(P<0.001)
BA:
-22.6%
Placebo:
-1.2%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-24.3%
(P<0.001)
BA:
-25.4%
Placebo:
+2.7%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Athralgia
(6.0% vs 4.5%)
Pain in extremity
(5.6% vs 3.6%)
Myalgia (4.7% vs 7.2%)
Prevalence of Serious AEs
(BA vs placebo)
6.0% vs 3.6%
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
18.4% vs 11.7%
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-28.5%
(P<0.001)
BA:
-23.5%
Placebo:
+5.0%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-31.0%
(P<0.001)
BA:
-32.5%
Placebo:
+2.1%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Blood uric acid increased
(7.7% vs 2.3%)
Prevalence of Serious AEs
(BA vs placebo)
2.8% vs 3.4%
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
6.1% vs 5.7%
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-29.0%
(P<0.001)
BA/EZE:
-31.5%
BA:
-17.7%
Ezetimibe:
-21.0%
Placebo:
-2.5%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-37.2%
(P<0.001)
BA/EZE:
-34.0%
BA:
-20.0%
Ezetimibe:
-8.5%
Placebo:
+4.0%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Urinary tract
infection (7.5% for BA/EZE, 2.7% for BA, 2.8% for EZE, 3.6% for placebo)
Nasopharyngitis
(3.7% for BA/EZE, 5.5% for BA, 3.7% for EZE, 1.8% for placebo)
Prevalence of Serious AEs
(BA vs placebo)
7.5% for BA/EZE FDC
9.2% for ezetimibe
6.4% for BA
1.8% for placebo
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
6.5% for BA/EZE
9.2% for ezetimibe
8.2% for BA
3.6% for placebo
 
CLEAR
Harmony
(1002-040)
(N=2,230)
(BA: n=1,488)
(placebo: n=742)
CLEAR
Wisdom
(1002-047)
(N=779)
(BA: n=522)
(placebo: n=257)
CLEAR
Serenity
(1002-046)
(N=345)
(BA: n=234)
(placebo: n=111)
CLEAR
Tranquility
(1002-048)
(N=269)
(BA: n=181)
(placebo: n=88)
Bempedoic Acid/Ezetimibe Combination Tablet
(1002FDC-053)
(N=382)
(BA/EZE: n=108)
(BA: n=110)
(EZE:
n=109)
(placebo: n=55)
LDL-C Reduction
(% reduction from baseline, placebo corrected)
-18.1%
(P<0.001)
BA:
-16.5%
Placebo:
+1.6%
-17.4%
(P<0.001)
BA:
-15.1%
Placebo:
+2.4%
-21.4%
(P<0.001)
BA:
-22.6%
Placebo:
-1.2%
-28.5%
(P<0.001)
BA:
-23.5%
Placebo:
+5.0%
-29.0%
(P<0.001)
BA/EZE:
-31.5%
BA:
-17.7%
Ezetimibe:
-21.0%
Placebo:
-2.5%
hsCRP Reduction
(median percentage change from baseline, placebo corrected)
-21.5%
(P<0.001)
BA:
-22.4%
Placebo:
+2.6%
-8.7%
(P<0.001)
BA:
-18.7%
Placebo:
-9.4%
-24.3%
(P<0.001)
BA:
-25.4%
Placebo:
+2.7%
-31.0%
(P<0.001)
BA:
-32.5%
Placebo:
+2.1%
-37.2%
(P<0.001)
BA/EZE:
-34.0%
BA:
-20.0%
Ezetimibe:
-8.5%
Placebo:
+4.0%
Prevalence of Most Common AEs
(≥5%, BA vs placebo)
Nasopharyngitis (9.8% vs 11.7%)
Myalgia (6.0% vs 6.1%)
Nasopharyngitis (5.2% vs 5.1%)
Urinary Tract
Infection
(5.0% vs 1.9%)
Athralgia
(6.0% vs 4.5%)
Pain in
extremity
(5.6% vs 3.6%)
Myalgia
(4.7% vs 7.2%)
Blood uric acid
increased
(7.7% vs 2.3%)
Urinary tract
infection
(7.5% for BA/EZE,
2.7% for BA,
2.8%
for EZE, 3.6% for placebo)
Nasopharyngitis
(3.7% for BA/EZE,
5.5% for BA, 3.7%
for
EZE, 1.8%
for placebo)
Prevalence of Serious AEs
(BA vs placebo)
12.4% vs
9.4%
20.3% vs
18.7%
6.0% vs
3.6%
2.8% vs
3.4%
7.5% for BA/EZE FDC
6.4% for BA
9.2% for ezetimibe
1.8% for placebo
Discontinuation of IMP Due to AEs
(percent, BA vs placebo)
10.9% vs
7.1%
10.9% vs
8.6%
18.4% vs
11.7%
6.1% vs
5.7%
6.5% for BA/EZE
8.2% for BA
9.2% for ezetimibe
3.6% for placebo
LDL-C=low-density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; BA=bempedoic acid;
EZE=ezetimibe; BA/EZE=bempedoic acid/ezetimibe combination tablet; FDC=fixed-dose combination;
AEs=adverse events; IMP=investigational medicinal product.
A Cardiovascular Outcomes Trial Is in Progress
In addition to the bempedoic acid Phase 3 clinical program, ESPERION has initiated a global cardiovascular outcomes trial (CVOT)—CLEAR Outcomes—and plans to submit the trial results to health
authorities in 2022 for inclusion in product labeling.
CV Risk Reduction Indication1
ASCVD/High-risk Primary Prevention
CLEAR Outcomes:
(N=~12,600)
4.75
years
CLEAR Outcomes (1002-043) is a cardiovascular event-driven, global, randomized, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients.2

CLEAR Outcomes takes place at more than 1,200 sites in 30 countries.2 The study is expected to enroll patients over a 30-month period, with a total estimated study duration of approximately 4.75 years.3

For a comprehensive look at inclusion and exclusion criteria, and endpoint information, please visit clinicaltrials.gov.

To See the Results of the Phase 2 Trials for Bempedoic Acid, Read Our Press Releases
Phase 2 trials are generally smaller and shorter than Phase 3 trials. They are designed as a preliminary exploration to help guide the design of the pivotal Phase 3 trials.

This 8-week study evaluated the LDL-C lowering efficacy and safety of bempedoic acid added on to background therapy with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

ESPERION Announces Positive Top-Line Results from Phase 2 Study of Bempedoic Acid Added-On to a PCSK9 Inhibitor in Patients with Hypercholesterolemia

This 6-week study evaluated the LDL-C lowering efficacy and safety of bempedoic acid/ezetimibe combination therapy plus atorvastatin 20 mg

ESPERION Announces Positive Top-Line Results From Phase 2 Study of Bempedoic Acid/Ezetimibe
Combination Plus Atorvastatin

For more information about our clinical trials, contact ESPERION Therapeutics, Inc. or visit clinicaltrials.gov.

Get updates about ESPERION and our clinical trials
References: 1. Data on file. ESPERION Therapeutics, Inc. 2019. 2. Evaluation of major cardiovascular events in patients with, or at high risk for, cardiovascular disease who are statin intolerant treated with bempedoic acid (ETC1002) or placebo (CLEAR Outcomes). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02993406. Accessed February 8, 2019. 3. M. Ruscica, M. Banach, A. Sahebkar, A. Corsini & C. R. Sirtori. ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials. Exp Opin Pharmacother. 2019. doi:10.1080/14656566.2019.1583209.