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

Hyperlipidemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02659397
• Other study ID #: 1002-035
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: July 2016

Study information

• Verified date: March 2019
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak plasma concentration (Cmax) pharmacokinetics of atorvastatin and its active metabolites	Fold change in Cmax from prior-to to following 2 week treatment with ETC-1002	2 weeks
Primary	24-hour area under the curve (AUC) pharmacokinetics of atorvastatin and its active metabolites	Fold change in AUC from prior-to to following 2 week treatment with ETC-1002	2 weeks
Primary	Percent change in LDL-cholesterol	Percent Change from baseline to 4 week treatment, incremental lowering of LDL-C	4 weeks
Secondary	Percent change in hsCRP	Percent change from baseline to following 4 week treatment with ETC-1002	4 weeks
Secondary	Percent change in total cholesterol	Percent change from baseline to following 4 week treatment with ETC-1002	4 weeks
Secondary	Percent change in non-HDL-cholesterol	Percent change from baseline to following 4 week treatment with ETC-1002	4 weeks
Secondary	Percent change in apolipoprotein B	Percent change from baseline to following 4 week treatment with ETC-1002	4 weeks
Secondary	24-hour post dose plasma concentration pharmacokinetics of ETC-1002 and its active metabolite	Fold change in trough exposure from prior-to to following 2 week treatment with ETC-1002	2 weeks