Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03193047
• Other study ID #: 1002-039
• Status: Completed
• Phase: Phase 2
• Start date: April 7, 2017
• Est. completion date: February 19, 2018

Study information

• Verified date: March 2020
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 19, 2018
• Est. primary completion date: January 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• bempedoic acid 180mg
Daily bempedoic acid 180mg tablet in addition to monthly PCSK9i (evolocumab) background therapy

Other:
• placebo
Daily matching placebo tablet in addition to monthly PCSK9i (evolocumab) background therapy

Drug:
• evolocumab
Monthly PCSK9i (evolocumab) background therapy

Locations

Country	Name	City	State
United States	L-MARC Research Center	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396. — View Citation

Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Month 2	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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA), with treatment group as a factor and Baseline as a covariate. Missing data were imputed using last observation carried forward (LOCF) (only post-Baseline values were carried forward).	Baseline; Month 2
Secondary	Percent Change From Baseline in LDL-C at Month 1	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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis.	Baseline; Month 1
Secondary	Absolute Change From Baseline in LDL-C at Month 1 and Month 2	Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the average of the Screening Visit 4 and the Day 1 value. If only 1 value is available, then that single value is used as Baseline. Change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.	Baseline; Month 1 and Month 2
Secondary	Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2	Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline apolipoprotein B (apoB) is defined as the Day 1 value. Baseline total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) are defined as the average of the Month -1 (Screening Visit 4) and the Day 1 (Treatment Visit 1) values. If a missing value presented at Month -1 or Day 1, then the last non-missing value prior to the first dose of double-blind study medication (including unscheduled assessments) within Month -1 and Day 1 was used to compute the Baseline measurements. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.	Baseline; Month 1 and Month 2
Secondary	Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2	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 Day 1 value. Percent change from Baseline was analyzed using a non-parametric approach. Missing Month 2 data were handled by LOCF. Observed data were used for analysis at Month 1.	Baseline; Month 1 and Month 2
Secondary	Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)	Treatment-emergent AEs (TEAEs) and SAEs (TESAEs) were reported and defined as any AE that began or worsened after the first dose of investigational medicinal product.	up to Month 2 (until 30 days after last dose)
Secondary	Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2	The number of participants with ALT or AST >3x ULN was measured.	Month 1 and Month 2

External Links

•   World Health Organization Fact Sheet No. 317