A Study of LY2484595 in Patients With High LDL-C or Low HDL-C

Study Overview
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Brief Summary
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The primary purpose of your participation in this study is to help answer the following research question(s) Whether LY2484595 in combination with a statin drug (atorvastatin, simvastatin or rosuvastatin; currently used to treat abnormal fat or cholesterol in blood) improves the blood fat profile more than statins alone. Whether LY2484595 alone improves blood fats profile compared to sugar pills. Whether LY2484595 interferes with break down or functioning of statins. Whether LY2484595 has any side effects that would not support testing it in future studies.

Detailed Description
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Patients will be stratified according to baseline levels of serum triglycerides (<150 or greater than or equal to 150 milligram/deciliter (mg/dL), HDL-C (<45 or greater than or equal to 45 mg/dL for men; <50 or greater than or equal to 50 mg/dL for women), and region (United States or Europe). After a diet lead-in and prior therapy washout phase, subjects meeting all entry criteria will be randomized to one of 10 double-blind treatment groups for a 12 week treatment phase. After randomization, patients will self-administer the study drugs once a day with a low fat meal as their first meal of the day.

Official Title
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A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: LY2484595
* Drug: Atorvastatin
* Drug: Simvastatin
* Drug: Rosuvastatin
* Drug: Placebo for LY2484595
* Drug: Placebo for Statins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Diagnosed with Low High Density Lipoprotein Cholesterol (HDL-C) or hypercholesterolemia, after diet lead-in/washout of lipid therapies Exclusion Criteria: History of coronary heart disease, or hardening of the arteries, or heart does not pump sufficiently well Hypertension or high blood pressure that is not under control or your study physician does not consider the electrical activity of heart (Electrocardiogram [ECG]) to be compatible with participation in the study History of a bad skin rash, a prior rash due to a drug or a history of chronic skin disorder (such as psoriasis or eczema) Intolerance to certain lipid modifying drugs (including statins and Cholesteryl Ester Transfer Protein (CETP) inhibitors) Not willing to stop taking prescription or over the counter drugs you use to control fats in your blood (like fish oil, niacin or statin) or pills to decrease your weight, including herbs Not willing to follow the diet (low-fat) that the study physician will recommend Have disease of liver, kidneys, muscles or other organs of body, a serious infection or cancer, or abnormal laboratory tests that study physician does not consider compatible with participation in the study Breastfeeding woman or a woman who can still become pregnant, but are not willing to use a valid birth control measure to prevent pregnancies

Ages Eligible for Study
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Minimum Age: 18 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: 30 milligram (mg) LY2484595 monotherapy<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for Statins<br>* Administered daily by mouth for 12 weeks<br>|
| Experimental: 100 mg LY2484595 monotherapy<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for Statins<br>* Administered daily by mouth for 12 weeks<br>|
| Experimental: 500 mg LY2484595 monotherapy<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for Statins<br>* Administered daily by mouth for 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo for LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for Statins<br>* Administered daily by mouth for 12 weeks<br>|
| Active Comparator: 20 mg Atorvastatin monotherapy<br> | Drug: Atorvastatin<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for LY2484595<br>* Administered daily by mouth for 12 weeks<br>|
| Experimental: 100 mg LY2484595 + 20 mg Atorvastatin<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Atorvastatin<br>* Administered daily by mouth for 12 weeks<br>|
| Active Comparator: 40 mg Simvastatin monotherapy<br> | Drug: Simvastatin<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for LY2484595<br>* Administered daily by mouth for 12 weeks<br>|
| Experimental: 100 mg LY2484595 + 40 mg Simvastatin<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Simvastatin<br>* Administered daily by mouth for 12 weeks<br>|
| Active Comparator: 10 mg Rosuvastatin monotherapy<br> | Drug: Rosuvastatin<br>* Administered daily by mouth for 12 weeks<br>Drug: Placebo for LY2484595<br>* Administered daily by mouth for 12 weeks<br>|
| Experimental: 100 mg LY2484595 + 10 mg Rosuvastatin<br> | Drug: LY2484595<br>* Administered daily by mouth for 12 weeks<br>Drug: Rosuvastatin<br>* Administered daily by mouth for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Simvastatin or Rosuvastatin and Simvastatin/Rosuvastatin Monotherapy | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Simvastatin or Rosuvastatin and Simvastatin/Rosuvastatin Monotherapy | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State |  | Baseline up to 12 weeks | 
| Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | All rash cases were adjudicated by a central dermatologist blinded to treatment assignment according to a study-specific Clinical Events Committee (CEC) charter. Rash events were assessed according to clinical relevance (high risk, low risk, not a relevant dermatosis, or insufficient documentation for determination). A participant could be reported in multiple categories. | Baseline through Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Serum Potassium | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Serum Sodium | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline, Week 12 | 
| Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | EQ-5D is a health-related, quality-of-life instrument. It allows participants to rate their health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score 1 -3 is generated for each domain, with 1=no problem and 3= extreme problems. The outcome ratings on the 5 domains are mapped to a single index through an algorithm. The index ranges 0-1, with the higher score indicating a better health state perceived by the participants. LS Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. | Baseline up to Week 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyslipidemias, Mixed dyslipidemia, Hypercholesterolemia, Atherosclerosis, Atorvastatin, Simvastatin, Rosuvastatin, Metabolic Diseases, Antilipemic Agents, Enzyme Inhibitors, Anticholesteremic Agents, Cholesteryl Ester Transfer Protein Inhibitors, Cholesteryl Ester, Lipid Metabolism Disorders