Clinical trial NCT03193047: Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy
Official title: A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg QD When Added to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: Cholesterol
PCSK9
Repatha
evolocumab
LDL-C
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-20
Enrollment: 59
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) 180mg added to PCSK9 inhibitor (evolocumab) therapy is effective and safe in patients with elevated LDL cholesterol.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years or legal age of majority depending on regional law
* Fasting, calculated LDL-C at screening ≥160 mg/dL and following PCSK9i therapy ≥70 mg/dL
* Men and nonpregnant, nonlactating women

Exclusion Criteria:

* Heterozygous (HeFH) or Homozygous (HoFH) Familial Hypercholesterolemia
* Total fasting TG ≥500 mg/dL
* Renal dysfunction or a glomerulonephropathy; eGFR \<30 mL/min/1.73 m2
* Known cardiovascular disease (CVD), peripheral arterial disease (PAD), or cerebrovascular disease (CD)
* History of type 1 or type 2 diabetes
* Uncontrolled hypertension
* Uncontrolled hypothyroidism
* Liver disease or dysfunction
* Gastrointestinal conditions or procedures (including Lap-Band® or gastric bypass)
* History of hematologic or coagulation disorders
* History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ)
* Unexplained creatine kinase (CK) \>3 × ULN
* Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, such as: anacetrapib, dalcetrapib, or evacetrapib
* Pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 30 days after the end of treatment

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Month 2
timeFrame: Baseline; Month 2
Secondary outcomes:
measure: Percent Change From Baseline in LDL-C at Month 1
timeFrame: Baseline; Month 1
measure: Absolute Change From Baseline in LDL-C at Month 1 and Month 2
timeFrame: Baseline; Month 1 and Month 2
measure: Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2
timeFrame: Baseline; Month 1 and Month 2
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2
timeFrame: Baseline; Month 1 and Month 2
measure: Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)
timeFrame: up to Month 2 (until 30 days after last dose)
measure: Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2
timeFrame: Month 1 and Month 2
Other outcomes:
Locations:
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
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: Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. No abstract available.
citation: Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W; Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001 Sep 4;104(10):1108-13. doi: 10.1161/hc3501.095214.
citation: Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. doi: 10.1001/jama.289.13.1681.