Clinical trial 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)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC 1002) 180 mg/Day as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Atherosclerosis
Statin Adverse Reaction
Keywords: hyperlididemia
LDL
cholesterol
statin intolerance
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-22
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Fasting LDL-cholesterol greater than or equal to 100 mg/dL at screening
* Men and nonpregnant, nonlactating women
* Use of stable lipid-modifying therapy for at least 4 weeks prior to screening that includes ezetimibe 10mg daily

Exclusion Criteria:

* Fasting blood triglycerides greater than or equal to 500 mg/dL
* Body Mass Index (BMI) greater than or equal to 50 kg/m2
* Recent history of clinically significant cardiovascular disease
* Use of statin therapy where doses are greater than those defined as "low-dose" within 4 weeks prior to screening; where "low-dose" is defined as an average daily dose of rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg, or pitavastatin 2 mg.

Primary outcomes:
measure: Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Week 12
Secondary outcomes:
measure: Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Week 12
measure: Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
timeFrame: Week 12
measure: Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
timeFrame: Week 12
measure: Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
timeFrame: Week 12
measure: Percent Change From Baseline to Week 12 in Triglycerides (TGs)
timeFrame: Week 12
measure: Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
timeFrame: Week 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 16 weeks
Other outcomes:
measure: Percent Change From Baseline to Weeks 4 and 8 in LDL-C
timeFrame: Week 4 and Week 8
measure: Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C
timeFrame: Week 4 and Week 8
measure: Percent Change From Baseline to Weeks 4 and 8 in TC
timeFrame: Week 4 and Week 8
measure: Percent Change From Baseline to Weeks 4 and 8 in TGs
timeFrame: Week 4 and Week 8
measure: Percent Change From Baseline to Weeks 4 and 8 in HDL-C
timeFrame: Week 4 and Week 8
measure: Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C
timeFrame: Week 4, Week 8 and Week 12
Locations:
city: Georgetown
country: United States
state: Texas
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Ron Haberman, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, Leiter LA. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018 Oct;277:195-203. doi: 10.1016/j.atherosclerosis.2018.06.002. Epub 2018 Jun 12.
citation: Ballantyne CM, Bays HE, Louie MJ, Smart J, Zhang Y, Ray KK. Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid. J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.
citation: Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Flaim J, Ye Z, Catapano AL. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol. 2020 Oct 1;5(10):1124-1135. doi: 10.1001/jamacardio.2020.2314.