A Study Of Pharmacokinetics, Pharmacodynamics And Safety Of Adding ETC-1002 To Atorvastatin 80 mg

Overview

The purpose of this research study is to measure the amount of atorvastatin and ETC-1002 in the blood, to determine how ETC-1002 affects the level of LDL-cholesterol (bad cholesterol) and other markers of health and disease in blood and urine, and to see how ETC-1002 is tolerated in the body compared to placebo when added to stable atorvastatin 80 mg background therapy in statin-treated patients.

Full Title of Study: “A Study to Assess the Pharmacokinetics, Pharmacodynamics and Safety of Adding ETC-1002 180 mg to Atorvastatin 80 mg Background Therapy in Statin-Treated Patients”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2016

Interventions

  • Drug: ETC-1002
    • Blinded ETC-1002 180 mg tablet once daily for 4 weeks (Weeks 1 to 4)
  • Drug: Atorvastatin
    • Atorvastatin 80 mg tablet once daily for 8 weeks (Weeks -4 to 4)
  • Drug: Placebo
    • Blinded ETC-1002-matched placebo tablet once daily for 4 weeks (Weeks 1 to 4)

Arms, Groups and Cohorts

  • Experimental: ETC-1002 + Atorvastatin
    • ETC-1002 180 mg treatment, oral once daily added-on to Atorvastatin 80 mg once daily
  • Placebo Comparator: Placebo + Atorvastatin
    • Placebo treatment, oral once daily added-on to Atorvastatin 80 mg once daily

Clinical Trial Outcome Measures

Primary Measures

  • Peak plasma concentration (Cmax) pharmacokinetics of atorvastatin and its active metabolites
    • Time Frame: 2 weeks
    • Fold change in Cmax from prior-to to following 2 week treatment with ETC-1002
  • 24-hour area under the curve (AUC) pharmacokinetics of atorvastatin and its active metabolites
    • Time Frame: 2 weeks
    • Fold change in AUC from prior-to to following 2 week treatment with ETC-1002
  • Percent change in LDL-cholesterol
    • Time Frame: 4 weeks
    • Percent Change from baseline to 4 week treatment, incremental lowering of LDL-C

Secondary Measures

  • Percent change in hsCRP
    • Time Frame: 4 weeks
    • Percent change from baseline to following 4 week treatment with ETC-1002
  • Percent change in total cholesterol
    • Time Frame: 4 weeks
    • Percent change from baseline to following 4 week treatment with ETC-1002
  • Percent change in non-HDL-cholesterol
    • Time Frame: 4 weeks
    • Percent change from baseline to following 4 week treatment with ETC-1002
  • Percent change in apolipoprotein B
    • Time Frame: 4 weeks
    • Percent change from baseline to following 4 week treatment with ETC-1002
  • 24-hour post dose plasma concentration pharmacokinetics of ETC-1002 and its active metabolite
    • Time Frame: 2 weeks
    • Fold change in trough exposure from prior-to to following 2 week treatment with ETC-1002

Participating in This Clinical Trial

Inclusion Criteria

  • Taking daily stable statin doses for at least 4 weeks prior to screening visit. – LDL-C between 100-220 mg/dL for patients taking daily high-intensity statin (for 4 weeks prior to switching to sponsor -provided atorvastatin 80 mg/day and stopping all other lipid-regulating drugs and supplements) at the screening visit; or, – LDL-C between 115-220 mg/dL for patients taking moderate- or low-intensity statin (for 4 weeks prior to switching to sponsor -provided atorvastatin 80 mg/day and stopping all other lipid-regulating drugs and supplements) at the screening visit. – Must be willing to discontinue other lipid-regulating therapies during the study Exclusion Criteria:

  • History of acute significant cardiovascular disease. – Current clinically significant cardiovascular disease. – History of inability to tolerate any statin at any dose due to muscle-related pain or weakness.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Esperion Therapeutics, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mary McGowan, MD, Study Director, Esperion Therapeutics, Inc.

References

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.

Nikolic D, Mikhailidis DP, Davidson MH, Rizzo M, Banach M. ETC-1002: a future option for lipid disorders? Atherosclerosis. 2014 Dec;237(2):705-10. doi: 10.1016/j.atherosclerosis.2014.10.099. Epub 2014 Oct 31.

Filippov S, Pinkosky SL, Newton RS. LDL-cholesterol reduction in patients with hypercholesterolemia by modulation of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase. Curr Opin Lipidol. 2014 Aug;25(4):309-15. doi: 10.1097/MOL.0000000000000091.

Gutierrez MJ, Rosenberg NL, Macdougall DE, Hanselman JC, Margulies JR, Strange P, Milad MA, McBride SJ, Newton RS. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):676-83. doi: 10.1161/ATVBAHA.113.302677. Epub 2014 Jan 2.

Ballantyne CM, Davidson MH, Macdougall DE, Bays HE, Dicarlo LA, Rosenberg NL, Margulies J, Newton RS. Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. J Am Coll Cardiol. 2013 Sep 24;62(13):1154-62. doi: 10.1016/j.jacc.2013.05.050. Epub 2013 Jun 13.

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