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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Drug: ETC-1002
* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETC-1002 + Atorvastatin<br>ETC-1002 180 mg treatment, oral once daily added-on to Atorvastatin 80 mg once daily | Drug: ETC-1002<br>* Blinded ETC-1002 180 mg tablet once daily for 4 weeks (Weeks 1 to 4)<br>* Other names: bempedoic acid;Drug: Atorvastatin<br>* Atorvastatin 80 mg tablet once daily for 8 weeks (Weeks -4 to 4)<br>|
| Placebo Comparator: Placebo + Atorvastatin<br>Placebo treatment, oral once daily added-on to Atorvastatin 80 mg once daily | Drug: Atorvastatin<br>* Atorvastatin 80 mg tablet once daily for 8 weeks (Weeks -4 to 4)<br>Drug: Placebo<br>* Blinded ETC-1002-matched placebo tablet once daily for 4 weeks (Weeks 1 to 4)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Percent change in LDL-cholesterol | Percent Change from baseline to 4 week treatment, incremental lowering of LDL-C | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in hsCRP | Percent change from baseline to following 4 week treatment with ETC-1002 | 4 weeks | 
| Percent change in total cholesterol | Percent change from baseline to following 4 week treatment with ETC-1002 | 4 weeks | 
| Percent change in non-HDL-cholesterol | Percent change from baseline to following 4 week treatment with ETC-1002 | 4 weeks | 
| Percent change in apolipoprotein B | Percent change from baseline to following 4 week treatment with ETC-1002 | 4 weeks | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL-cholesterol, Hypercholesterolemia, ETC-1002, Adenosine triphosphate citrate lyase, Atorvastatin