Dyslipidemia
Conditions
Keywords
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
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.
Interventions
DRUGRosuvastatin
Administered daily by mouth for 12 weeks
DRUGPlacebo for LY2484595
Administered daily by mouth for 12 weeks
DRUGPlacebo for Statins
Administered daily by mouth for 12 weeks
DRUGLY2484595
Administered daily by mouth for 12 weeks
DRUGAtorvastatin
Administered daily by mouth for 12 weeks
DRUGSimvastatin
Administered daily by mouth for 12 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | Baseline, 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 Monotherapy | Baseline, Week 12 | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, 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 Monotherapy | Baseline, 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-State | Baseline up to 12 weeks | — |
| Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | Baseline, 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) Mass | Baseline, 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 12 | 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. |
| Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | 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 Aldosterone | 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 Plasma Renin Activity | 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 Potassium | 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 Sodium | 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 Bicarbonate | 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 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | Baseline 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. |
| 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. |
| Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | Baseline, Week 12 | Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction. |
Countries
Denmark, Germany, Netherlands, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 30 mg LY2484595 Monotherapy Administered daily by mouth for 12 weeks | 40 |
| 100 mg LY2484595 Monotherapy Administered daily by mouth for 12 weeks | 38 |
| 500 mg LY2484595 Monotherapy Administered daily by mouth for 12 weeks | 40 |
| Placebo Administered daily by mouth for 12 weeks | 38 |
| 20 mg Atorvastatin Monotherapy Administered daily by mouth for 12 weeks | 41 |
| 100 mg LY2484595 + 20 mg Atorvastatin Administered daily by mouth for 12 weeks | 35 |
| 40 mg Simvastatin Monotherapy Administered daily by mouth for 12 weeks | 41 |
| 100 mg LY2484595 + 40 mg Simvastatin Administered daily by mouth for 12 weeks | 40 |
| 10 mg Rosuvastatin Monotherapy Administered daily by mouth for 12 weeks | 39 |
| 100 mg LY2484595 + 10 mg Rosuvastatin Administered daily by mouth for 12 weeks | 41 |
| Total | 393 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal Lab/Electrocardiogram Result | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 1 | 2 | 0 |
| Overall Study | Adverse Event | 2 | 1 | 5 | 1 | 0 | 1 | 2 | 4 | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 2 | 0 | 1 | 1 | 1 | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 | 0 | 4 | 1 | 2 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | 30 mg LY2484595 Monotherapy | 100 mg LY2484595 Monotherapy | 500 mg LY2484595 Monotherapy | Placebo | 20 mg Atorvastatin Monotherapy | 100 mg LY2484595 + 20 mg Atorvastatin | 40 mg Simvastatin Monotherapy | 100 mg LY2484595 + 40 mg Simvastatin | 10 mg Rosuvastatin Monotherapy | 100 mg LY2484595 + 10 mg Rosuvastatin | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 11.1 | 58.5 years STANDARD_DEVIATION 9.2 | 58.8 years STANDARD_DEVIATION 12.2 | 55.2 years STANDARD_DEVIATION 10.5 | 57.8 years STANDARD_DEVIATION 11.3 | 57.4 years STANDARD_DEVIATION 11.8 | 61.3 years STANDARD_DEVIATION 10 | 58.4 years STANDARD_DEVIATION 9 | 57.4 years STANDARD_DEVIATION 12.6 | 59.7 years STANDARD_DEVIATION 10.1 | 58.3 years STANDARD_DEVIATION 10.8 |
| Body Mass Index (BMI) | 29.8 kilogram/square meter (kg/m²) STANDARD_DEVIATION 7.8 | 27.6 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.7 | 29.0 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.6 | 29.8 kilogram/square meter (kg/m²) STANDARD_DEVIATION 6.1 | 28.8 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.1 | 30.0 kilogram/square meter (kg/m²) STANDARD_DEVIATION 7.5 | 28.3 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5 | 29.9 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.3 | 28.3 kilogram/square meter (kg/m²) STANDARD_DEVIATION 4.2 | 28.4 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.3 | 29.0 kilogram/square meter (kg/m²) STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 28 Participants | 29 Participants | 26 Participants | 29 Participants | 25 Participants | 29 Participants | 30 Participants | 25 Participants | 34 Participants | 282 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 7 Participants | 9 Participants | 9 Participants | 10 Participants | 8 Participants | 10 Participants | 9 Participants | 13 Participants | 6 Participants | 92 Participants |
| Fasting Triglycerides | 133.9 mg/dL STANDARD_DEVIATION 56.6 | 129.8 mg/dL STANDARD_DEVIATION 51.7 | 133.1 mg/dL STANDARD_DEVIATION 69.8 | 154.4 mg/dL STANDARD_DEVIATION 93 | 144.1 mg/dL STANDARD_DEVIATION 83.4 | 133.0 mg/dL STANDARD_DEVIATION 67.8 | 145.3 mg/dL STANDARD_DEVIATION 84.6 | 142.4 mg/dL STANDARD_DEVIATION 62.4 | 142.8 mg/dL STANDARD_DEVIATION 65.6 | 138.1 mg/dL STANDARD_DEVIATION 69 | 139.8 mg/dL STANDARD_DEVIATION 71.1 |
| High-Density Lipoprotein Cholesterol (HDL-C) | 54.7 milligram/deciliter (mg/dL) STANDARD_DEVIATION 12 | 57.0 milligram/deciliter (mg/dL) STANDARD_DEVIATION 14.1 | 54.7 milligram/deciliter (mg/dL) STANDARD_DEVIATION 16.3 | 53.0 milligram/deciliter (mg/dL) STANDARD_DEVIATION 11.8 | 53.9 milligram/deciliter (mg/dL) STANDARD_DEVIATION 17 | 55.7 milligram/deciliter (mg/dL) STANDARD_DEVIATION 18.2 | 57.3 milligram/deciliter (mg/dL) STANDARD_DEVIATION 16.2 | 53.7 milligram/deciliter (mg/dL) STANDARD_DEVIATION 13.6 | 53.5 milligram/deciliter (mg/dL) STANDARD_DEVIATION 15.2 | 57.8 milligram/deciliter (mg/dL) STANDARD_DEVIATION 18.1 | 55.1 milligram/deciliter (mg/dL) STANDARD_DEVIATION 15.3 |
| Low-Density Lipoprotein Cholesterol (LDL-C) | 143.5 mg/dL STANDARD_DEVIATION 26 | 148.0 mg/dL STANDARD_DEVIATION 25 | 135.7 mg/dL STANDARD_DEVIATION 26 | 147.3 mg/dL STANDARD_DEVIATION 21.6 | 139.0 mg/dL STANDARD_DEVIATION 26.7 | 143.6 mg/dL STANDARD_DEVIATION 26 | 154.8 mg/dL STANDARD_DEVIATION 35.1 | 143.7 mg/dL STANDARD_DEVIATION 29.1 | 141.6 mg/dL STANDARD_DEVIATION 23.8 | 145.7 mg/dL STANDARD_DEVIATION 21.8 | 144.3 mg/dL STANDARD_DEVIATION 26.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 36 Participants | 35 Participants | 36 Participants | 39 Participants | 33 Participants | 39 Participants | 39 Participants | 35 Participants | 40 Participants | 365 Participants |
| Region of Enrollment Denmark | 12 Participants | 9 Participants | 8 Participants | 10 Participants | 10 Participants | 9 Participants | 12 Participants | 11 Participants | 11 Participants | 10 Participants | 102 Participants |
| Region of Enrollment Germany | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 11 Participants |
| Region of Enrollment Netherlands | 2 Participants | 2 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 6 Participants | 2 Participants | 4 Participants | 4 Participants | 39 Participants |
| Region of Enrollment Poland | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 16 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants |
| Region of Enrollment United States | 22 Participants | 23 Participants | 22 Participants | 22 Participants | 23 Participants | 18 Participants | 21 Participants | 23 Participants | 22 Participants | 22 Participants | 218 Participants |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 21 Participants | 20 Participants | 26 Participants | 18 Participants | 29 Participants | 25 Participants | 13 Participants | 23 Participants | 220 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 19 Participants | 18 Participants | 15 Participants | 17 Participants | 12 Participants | 15 Participants | 26 Participants | 18 Participants | 173 Participants |
| Weight | 84.6 kilogram STANDARD_DEVIATION 23.2 | 79.9 kilogram STANDARD_DEVIATION 18.3 | 82.6 kilogram STANDARD_DEVIATION 20.6 | 89.3 kilogram STANDARD_DEVIATION 18.5 | 81.4 kilogram STANDARD_DEVIATION 16.4 | 87.4 kilogram STANDARD_DEVIATION 22.4 | 79.6 kilogram STANDARD_DEVIATION 15.4 | 84.5 kilogram STANDARD_DEVIATION 16.7 | 85.7 kilogram STANDARD_DEVIATION 19.4 | 82.2 kilogram STANDARD_DEVIATION 18 | 83.6 kilogram STANDARD_DEVIATION 19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 40 | 25 / 38 | 21 / 40 | 23 / 38 | 29 / 41 | 22 / 35 | 29 / 41 | 27 / 40 | 31 / 39 | 27 / 41 | 7 / 40 | 4 / 38 | 6 / 40 | 8 / 38 | 6 / 41 | 8 / 35 | 7 / 41 | 4 / 40 | 6 / 39 | 5 / 41 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 | 1 / 40 | 0 / 38 | 0 / 41 | 1 / 35 | 1 / 41 | 0 / 40 | 0 / 39 | 1 / 41 | 0 / 40 | 0 / 38 | 1 / 40 | 1 / 38 | 0 / 41 | 0 / 35 | 0 / 41 | 0 / 40 | 0 / 39 | 0 / 41 |
Outcome results
Primary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 HDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | 1.4 percent change of mg/dL | Standard Error 5.7 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | 79.9 percent change of mg/dL | Standard Error 6 |
p-value: <0.00190% CI: [64.9, 92.1]mixed model repeated measures (MMRM)
Primary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 LDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | -33.6 percent change of mg/dL | Standard Error 3 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy | -47.6 percent change of mg/dL | Standard Error 3.2 |
p-value: 0.00290% CI: [-21.2, -6.7]mixed model repeated measures (MMRM)
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 BP measurements.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 1.1 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 4.4 millimeters of mercury (mmHg) | Standard Error 1.8 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 0.8 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 4.3 millimeters of mercury (mmHg) | Standard Error 1.8 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 1.2 millimeters of mercury (mmHg) | Standard Error 1.2 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 1.4 millimeters of mercury (mmHg) | Standard Error 1.8 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 1.6 millimeters of mercury (mmHg) | Standard Error 1.1 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 2.8 millimeters of mercury (mmHg) | Standard Error 1.7 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 0.2 millimeters of mercury (mmHg) | Standard Error 1.7 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 0.2 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 2.1 millimeters of mercury (mmHg) | Standard Error 1.9 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 1.2 millimeters of mercury (mmHg) | Standard Error 1.2 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 0.0 millimeters of mercury (mmHg) | Standard Error 1.7 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | -1.5 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 2.3 millimeters of mercury (mmHg) | Standard Error 1.2 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 2.3 millimeters of mercury (mmHg) | Standard Error 1.8 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | 2.2 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 0.0 millimeters of mercury (mmHg) | Standard Error 1.8 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Diastolic BP | -0.1 millimeters of mercury (mmHg) | Standard Error 1.1 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Blood Pressure (BP) | Systolic BP | 3.8 millimeters of mercury (mmHg) | Standard Error 1.8 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 renin activity measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.06 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.11 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.58 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.35 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.30 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.58 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.26 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.37 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.16 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | 0.00 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.34 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.86 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.33 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Plasma Renin Activity | -0.29 nanograms/milliliter/hour (ng/mL/h) | Standard Error 0.35 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 aldosterone measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -0.5 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | 1.0 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -0.3 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -1.0 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -1.0 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | 0.4 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | 0.0 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -1.7 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | -2.5 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Aldosterone | 0.0 nanogram/deciliter (ng/dL) | Standard Error 0.9 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 bicarbonate measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.40 milliequivalents/Liter | Standard Error 0.36 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.60 milliequivalents/Liter | Standard Error 0.36 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.51 milliequivalents/Liter | Standard Error 0.37 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.27 milliequivalents/Liter | Standard Error 0.36 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.10 milliequivalents/Liter | Standard Error 0.36 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.58 milliequivalents/Liter | Standard Error 0.38 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 1.04 milliequivalents/Liter | Standard Error 0.35 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.58 milliequivalents/Liter | Standard Error 0.37 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 0.78 milliequivalents/Liter | Standard Error 0.36 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Bicarbonate | 1.25 milliequivalents/Liter | Standard Error 0.37 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 potassium measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | -0.04 milliequivalents/Liter | Standard Error 0.05 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | 0.01 milliequivalents/Liter | Standard Error 0.05 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | -0.02 milliequivalents/Liter | Standard Error 0.05 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | -0.08 milliequivalents/Liter | Standard Error 0.05 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | 0.09 milliequivalents/Liter | Standard Error 0.05 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | 0.08 milliequivalents/Liter | Standard Error 0.05 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | 0.03 milliequivalents/Liter | Standard Error 0.05 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | 0.02 milliequivalents/Liter | Standard Error 0.05 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | -0.07 milliequivalents/Liter | Standard Error 0.05 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Potassium | -0.05 milliequivalents/Liter | Standard Error 0.05 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 sodium measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.3 milliequivalents/Liter | Standard Error 0.4 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.3 milliequivalents/Liter | Standard Error 0.4 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.5 milliequivalents/Liter | Standard Error 0.4 |
| Placebo | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.1 milliequivalents/Liter | Standard Error 0.4 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 1.3 milliequivalents/Liter | Standard Error 0.4 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.6 milliequivalents/Liter | Standard Error 0.4 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.8 milliequivalents/Liter | Standard Error 0.4 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.9 milliequivalents/Liter | Standard Error 0.4 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.5 milliequivalents/Liter | Standard Error 0.4 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 12 Weeks Endpoint in Serum Sodium | 0.3 milliequivalents/Liter | Standard Error 0.4 |
Secondary
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.
Time frame: Baseline up to Week 18
Population: Participants who had both baseline and at least one post-baseline EQ-5D measurements, last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | 0.008 units on a scale | Standard Error 0.014 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | 0.002 units on a scale | Standard Error 0.014 |
| 500 mg LY2484595 Monotherapy | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | 0.012 units on a scale | Standard Error 0.014 |
| Placebo | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.001 units on a scale | Standard Error 0.014 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.002 units on a scale | Standard Error 0.014 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.006 units on a scale | Standard Error 0.014 |
| 40 mg Simvastatin Monotherapy | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.001 units on a scale | Standard Error 0.014 |
| 100 mg LY2484595 + 40 mg Simvastatin | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.001 units on a scale | Standard Error 0.013 |
| 10 mg Rosuvastatin Monotherapy | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | 0.014 units on a scale | Standard Error 0.014 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Change From Baseline to 18 Weeks Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) Score | -0.047 units on a scale | Standard Error 0.013 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 HDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | 53.6 percent change of mg/dL | Standard Error 5.6 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | 94.6 percent change of mg/dL | Standard Error 5.7 |
| 500 mg LY2484595 Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | 128.8 percent change of mg/dL | Standard Error 5.8 |
| Placebo | Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 and Placebo | -3.0 percent change of mg/dL | Standard Error 5.6 |
p-value: <0.00190% CI: [43.6, 69.8]mixed model repeated measures (MMRM)
p-value: <0.00190% CI: [84.5, 110.8]mixed model repeated measures (MMRM)
p-value: <0.00190% CI: [118.5, 145.2]mixed model repeated measures (MMRM)
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 HDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | 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 | 7.3 percent change of mg/dL | Standard Error 5.5 |
| 100 mg LY2484595 + 20 mg Atorvastatin | 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 | 86.6 percent change of mg/dL | Standard Error 5.7 |
| 500 mg LY2484595 Monotherapy | 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 | 5.5 percent change of mg/dL | Standard Error 5.7 |
| Placebo | 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 | 94.0 percent change of mg/dL | Standard Error 5.7 |
p-value: <0.00190% CI: [66.2, 92.4]mixed model repeated measures (MMRM)
p-value: <0.00190% CI: [75.2, 101.8]mixed model repeated measures (MMRM)
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 LDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | -13.6 percent change of mg/dL | Standard Error 3 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | -22.3 percent change of mg/dL | Standard Error 3 |
| 500 mg LY2484595 Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | -35.9 percent change of mg/dL | Standard Error 3.1 |
| Placebo | Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo | 3.9 percent change of mg/dL | Standard Error 3 |
p-value: <0.00190% CI: [-24.6, -10.5]mixed model repeated measures (MMRM)
p-value: <0.00190% CI: [-33.2, -19.2]mixed model repeated measures (MMRM)
p-value: <0.00190% CI: [-47, -32.7]mixed model repeated measures (MMRM)
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 LDL-C measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | 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 | -34.9 percent change of mg/dL | Standard Error 3 |
| 100 mg LY2484595 + 20 mg Atorvastatin | 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 | -46.1 percent change of mg/dL | Standard Error 3.1 |
| 500 mg LY2484595 Monotherapy | 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 | -38.8 percent change of mg/dL | Standard Error 3 |
| Placebo | 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 | -52.3 percent change of mg/dL | Standard Error 3 |
p-value: 0.00990% CI: [-18.3, -4.2]mixed model repeated measures (MMRM)
p-value: 0.00290% CI: [-20.6, -6.4]mixed model repeated measures (MMRM)
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 CETP activity measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -49.48 percent change of picomoles/mL/minute | Standard Error 3.75 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -70.80 percent change of picomoles/mL/minute | Standard Error 3.89 |
| 500 mg LY2484595 Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -89.10 percent change of picomoles/mL/minute | Standard Error 4 |
| Placebo | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | 12.12 percent change of picomoles/mL/minute | Standard Error 3.75 |
| 100 mg LY2484595 + 40 mg Simvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -0.01 percent change of picomoles/mL/minute | Standard Error 3.81 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -72.00 percent change of picomoles/mL/minute | Standard Error 4.01 |
| 40 mg Simvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -2.23 percent change of picomoles/mL/minute | Standard Error 3.8 |
| 100 mg LY2484595 + 40 mg Simvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -64.64 percent change of picomoles/mL/minute | Standard Error 3.86 |
| 10 mg Rosuvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -7.19 percent change of picomoles/mL/minute | Standard Error 3.8 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity | -73.24 percent change of picomoles/mL/minute | Standard Error 3.96 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Participants who had both baseline and Week 12 CETP mass measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 63.94 percent change of micrograms/mL (mcg/mL) | Standard Error 5.54 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 92.27 percent change of micrograms/mL (mcg/mL) | Standard Error 5.59 |
| 500 mg LY2484595 Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 136.66 percent change of micrograms/mL (mcg/mL) | Standard Error 5.83 |
| Placebo | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 0.58 percent change of micrograms/mL (mcg/mL) | Standard Error 5.51 |
| 100 mg LY2484595 + 40 mg Simvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | -11.8 percent change of micrograms/mL (mcg/mL) | Standard Error 5.48 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 62.98 percent change of micrograms/mL (mcg/mL) | Standard Error 5.87 |
| 40 mg Simvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | -11.14 percent change of micrograms/mL (mcg/mL) | Standard Error 5.5 |
| 100 mg LY2484595 + 40 mg Simvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 65.92 percent change of micrograms/mL (mcg/mL) | Standard Error 5.63 |
| 10 mg Rosuvastatin Monotherapy | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | -16.58 percent change of micrograms/mL (mcg/mL) | Standard Error 5.62 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Percent Change From Baseline to 12 Weeks Endpoint in Plasma Cholesteryl Ester Transfer Protein (CETP) Mass | 64.08 percent change of micrograms/mL (mcg/mL) | Standard Error 5.81 |
Secondary
Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State
Time frame: Baseline up to 12 weeks
Population: Participants who were administered LY2484595 and had pharmacokinetics (PK) samples.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 2300 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| 100 mg LY2484595 + 20 mg Atorvastatin | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 5900 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| 500 mg LY2484595 Monotherapy | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 19700 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| Placebo | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 5500 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| 100 mg LY2484595 + 40 mg Simvastatin | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 5620 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| 100 mg LY2484595 + 10 mg Rosuvastatin | Pharmacokinetics - LY2484595 Area Under the Concentration-Time Curve (AUC) at Steady-State | 5960 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
Secondary
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.
Time frame: Baseline through Week 12
Population: Participants who took study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20 mg Atorvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 4 events |
| 20 mg Atorvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 20 mg Atorvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 20 mg Atorvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 20 mg Atorvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 20 mg Atorvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 20 mg Atorvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 20 mg Atorvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 100 mg LY2484595 + 20 mg Atorvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 100 mg LY2484595 + 20 mg Atorvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 5 events |
| 500 mg LY2484595 Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 500 mg LY2484595 Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 500 mg LY2484595 Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 500 mg LY2484595 Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 3 events |
| 500 mg LY2484595 Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| Placebo | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 0 events |
| Placebo | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| Placebo | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| Placebo | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| Placebo | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 1 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 2 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 40 mg Simvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 40 mg Simvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 6 events |
| 40 mg Simvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 40 mg Simvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 1 events |
| 40 mg Simvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 1 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 4 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 100 mg LY2484595 + 40 mg Simvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 10 mg Rosuvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 10 mg Rosuvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 0 events |
| 10 mg Rosuvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 0 events |
| 10 mg Rosuvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 0 events |
| 10 mg Rosuvastatin Monotherapy | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Not a Relevant Dermatoses | 1 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | High Risk (HR)- Angioedema | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Insufficient Documentation for Determination | 0 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | HR - Insufficient Documentation for Determination | 1 events |
| 100 mg LY2484595 + 10 mg Rosuvastatin | The Number of Episodes of Rashes at Any Time From Baseline Through Week 12 | Low Risk | 2 events |