Clinical trial NCT02659397: A Study Of Pharmacokinetics, Pharmacodynamics And Safety Of Adding ETC-1002 To Atorvastatin 80 mg
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperlipidemia
Keywords: LDL-cholesterol
Hypercholesterolemia
ETC-1002
Adenosine triphosphate citrate lyase
Atorvastatin
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Peak plasma concentration (Cmax) pharmacokinetics of atorvastatin and its active metabolites
timeFrame: 2 weeks
measure: 24-hour area under the curve (AUC) pharmacokinetics of atorvastatin and its active metabolites
timeFrame: 2 weeks
measure: Percent change in LDL-cholesterol
timeFrame: 4 weeks
Secondary outcomes:
measure: Percent change in hsCRP
timeFrame: 4 weeks
measure: Percent change in total cholesterol
timeFrame: 4 weeks
measure: Percent change in non-HDL-cholesterol
timeFrame: 4 weeks
measure: Percent change in apolipoprotein B
timeFrame: 4 weeks
measure: 24-hour post dose plasma concentration pharmacokinetics of ETC-1002 and its active metabolite
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Northridge
country: United States
state: California
city: Clearwater
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Berlin
country: United States
state: New Jersey
city: Rapid City
country: United States
state: South Dakota
city: Carrollton
country: United States
state: Texas
city: West Jordan
country: United States
state: Utah
city: Arlington
country: United States
state: Virginia
city: Lynchburg
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Renton
country: United States
state: Washington
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Mary McGowan, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
citation: 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.