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

NCT03193047 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1002-039
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia

Keywords

Cholesterol; PCSK9; Repatha; evolocumab; LDL-C

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percent Change From Baseline in LDL-C at Month 1

  Baseline; Month 1

• Absolute Change From Baseline in LDL-C at Month 1 and Month 2

  Baseline; Month 1 and Month 2

• Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2

  Baseline; Month 1 and Month 2

• Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2

  Baseline; Month 1 and Month 2

• Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)

  up to Month 2 (until 30 days after last dose)

Study Arms (2)

bempedoic acid

EXPERIMENTAL

Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly

Drug: bempedoic acid 180mg; Drug: evolocumab

placebo

PLACEBO COMPARATOR

Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly

Other: placebo; Drug: evolocumab

Interventions

bempedoic acid 180mg DRUG

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

Also known as: ETC-1002

bempedoic acid

placebo OTHER

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

placebo

evolocumab DRUG

Monthly PCSK9i (evolocumab) background therapy

Also known as: Repatha

bempedoic acid; placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead

Study Sites (1)

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Related 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.

  PMID: 27892461 BACKGROUND

• 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.

  PMID: 24222016 BACKGROUND

• 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.

  PMID: 11535564 BACKGROUND

• Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. doi: 10.1001/jama.289.13.1681.

  PMID: 12672737 BACKGROUND

Related Links

• World Health Organization Fact Sheet No. 317

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; evolocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Esperion Therapeutics, Inc.

medinfo@esperion.com

1-833-377-7633

Study Officials

• Ron Haberman, MD

  Esperion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 20, 2017
• Study Start: April 7, 2017
• Primary Completion: January 29, 2018
• Study Completion: February 19, 2018
• Last Updated: April 3, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)