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

Phase 2
Completed
Conditions
Dyslipidemia
Interventions
Drug: Placebo for LY2484595
Drug: Placebo for Statins
Registration Number
NCT01105975
Lead Sponsor
Eli Lilly and Company
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
398
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
10 mg Rosuvastatin monotherapyPlacebo for LY2484595-
100 mg LY2484595 monotherapyPlacebo for Statins-
100 mg LY2484595 + 10 mg RosuvastatinLY2484595-
30 milligram (mg) LY2484595 monotherapyPlacebo for Statins-
20 mg Atorvastatin monotherapyPlacebo for LY2484595-
40 mg Simvastatin monotherapyPlacebo for LY2484595-
100 mg LY2484595 + 40 mg SimvastatinLY2484595-
100 mg LY2484595 monotherapyLY2484595-
PlaceboPlacebo for Statins-
30 milligram (mg) LY2484595 monotherapyLY2484595-
500 mg LY2484595 monotherapyLY2484595-
500 mg LY2484595 monotherapyPlacebo for Statins-
PlaceboPlacebo for LY2484595-
100 mg LY2484595 + 20 mg AtorvastatinLY2484595-
100 mg LY2484595 + 20 mg AtorvastatinAtorvastatin-
100 mg LY2484595 + 10 mg RosuvastatinRosuvastatin-
20 mg Atorvastatin monotherapyAtorvastatin-
40 mg Simvastatin monotherapySimvastatin-
100 mg LY2484595 + 40 mg SimvastatinSimvastatin-
10 mg Rosuvastatin monotherapyRosuvastatin-
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin MonotherapyBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin MonotherapyBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and PlaceboBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

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 MonotherapyBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) ActivityBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) MassBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to 12 Weeks Endpoint in Serum SodiumBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and PlaceboBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-StateBaseline up to 12 weeks
Change From Baseline to 12 Weeks Endpoint in Serum BicarbonateBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) ScoreBaseline up to Week 18

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.

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 MonotherapyBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP)Baseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to 12 Weeks Endpoint in Serum PotassiumBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

The Number of Episodes of Rashes at Any Time From Baseline Through Week 12Baseline 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.

Change From Baseline to 12 Weeks Endpoint in Serum AldosteroneBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to 12 Weeks Endpoint in Plasma Renin ActivityBaseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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Birmingham, United Kingdom

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