Hypercholesterolemia
Conditions
Keywords
LDL, HDL
Brief summary
The purpose of this study is to determine if Pitavastatin lowers CoQ10 less than Atorvastatin or Rosuvastatin.
Detailed description
Statins are known effectively treat high cholesterol and heart disease. However, statins may lower endogenous levels of Coenzyme10 (CoQ10). This decrease in CoQ10 levels may be responsible for side effects such as myalgia. Previous studies have shown that Pitavastatin may not affect CoQ10 levels as other statins do, while still lowering cholesterol. In this study, investigators intend to compare the plasma levels of CoQ10 in patients taking 3 different FDA-approved statins, in equipotent doses.
Interventions
Sponsors
Kowa Pharmaceuticals America, Inc.
Eli Lilly and Company
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* LDL-C levels of 100-200mg/dl; triglycerides \</=200mg/dl at screening visit * Willing to discontinue use of all lipid-altering doses fo medication or supplements for the duration of the study
Exclusion criteria
* LDL-C \<100mg/dl or \>200mg/dl, Triglycerides \>200mg/dl * History of diabetes mellitus or documented fasting blood glucose \>125mg/dl or HbA1c \>6.4% * History of coronary artery disease * history of chronic renal or hepatic disease * known sensitivity of intolerance to a statin * persistent elevated liver enzymes or CPK (\>3 x upper normal limit) * currently taking CoQ10 supplements and unable discontinue for duration of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Plasma CoQ10 Levels | Change from Baseline to 12 Weeks | Change in levels will be measured by taking difference between Baseline and Week 12 measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Major Lipid Parameters - VLDL Size | Change from Baseline to 12 Weeks | Change in levels will be measured by difference in levels at 12 weeks. Measure based on VLDL size. |
| Changes to Glucose Metabolism - HbA1c and Insulin | Change from Baseline to 12 weeks | Change in levels will be measured by levels at 12 weeks minus levels at baseline. Changes measured based in HbA1c, and insulin. |
| Changes in HDL and LDL Size | Change from Baseline to 12 Weeks | Change in levels will be measured by difference in levels at 12 weeks |
| Changes to Glucose Metabolism - Fructosamine | Change from Baseline to 12 weeks | Change in levels will be measured by levels at 12 weeks minus levels at baseline. Changes measured based in fructosamine. |
| Changes HDL Particle Number and LDL Particle Number | Change from Baseline to 12 Weeks | Change in levels will be measured by difference in levels at 12 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin 20mg Atorvastatin 20mg, once daily by mouth for 12 weeks | 45 |
| Pitavastatin 4mg Pitavastatin 4mg, once daily by mouth for 12 weeks | 45 |
| Rosuvastatin 5 mg Rosuvastatin 5mg, once daily by mouth for 12 weeks | 44 |
| Total | 134 |
Baseline characteristics
| Characteristic | Atorvastatin 20mg | Pitavastatin 4mg | Rosuvastatin 5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 54.68 years STANDARD_DEVIATION 12.52 | 56.66 years STANDARD_DEVIATION 9.93 | 56.08 years STANDARD_DEVIATION 12.28 | 55.80 years STANDARD_DEVIATION 11.57 |
| Gender Female | 28 Participants | 30 Participants | 36 Participants | 94 Participants |
| Gender Male | 17 Participants | 15 Participants | 8 Participants | 40 Participants |
| Region of Enrollment United States | 45 participants | 45 participants | 44 participants | 134 participants |
| Waist Size | 36.41 inches STANDARD_DEVIATION 5.76 | 37.45 inches STANDARD_DEVIATION 4.2 | 34.54 inches STANDARD_DEVIATION 5.6 | 36.12 inches STANDARD_DEVIATION 5.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 45 | 2 / 45 | 5 / 44 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 | 0 / 44 |
Outcome results
Primary
Changes in Plasma CoQ10 Levels
Change in levels will be measured by taking difference between Baseline and Week 12 measures.
Time frame: Change from Baseline to 12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin 20mg | Changes in Plasma CoQ10 Levels | Ubiquinone | -96.70 μg/g | Standard Deviation 224.24 |
| Atorvastatin 20mg | Changes in Plasma CoQ10 Levels | Upiquinol | -624.39 μg/g | Standard Deviation 669.45 |
| Atorvastatin 20mg | Changes in Plasma CoQ10 Levels | Total CoQ10 | -721.09 μg/g | Standard Deviation 830.47 |
| Pitavastatin 4mg | Changes in Plasma CoQ10 Levels | Ubiquinone | -110.42 μg/g | Standard Deviation 136.29 |
| Pitavastatin 4mg | Changes in Plasma CoQ10 Levels | Total CoQ10 | -464.85 μg/g | Standard Deviation 571.37 |
| Pitavastatin 4mg | Changes in Plasma CoQ10 Levels | Upiquinol | -354.43 μg/g | Standard Deviation 544.42 |
| Rosuvastatin 5 mg | Changes in Plasma CoQ10 Levels | Ubiquinone | -103.91 μg/g | Standard Deviation 237.27 |
| Rosuvastatin 5 mg | Changes in Plasma CoQ10 Levels | Upiquinol | -538.52 μg/g | Standard Deviation 709.53 |
| Rosuvastatin 5 mg | Changes in Plasma CoQ10 Levels | Total CoQ10 | -642.43 μg/g | Standard Deviation 874.99 |
Secondary
Changes HDL Particle Number and LDL Particle Number
Change in levels will be measured by difference in levels at 12 weeks.
Time frame: Change from Baseline to 12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin 20mg | Changes HDL Particle Number and LDL Particle Number | HDL Particle Number | 0.64 particle number | Standard Deviation 5.24 |
| Atorvastatin 20mg | Changes HDL Particle Number and LDL Particle Number | LDL Particle Number | -873.48 particle number | Standard Deviation 353.76 |
| Pitavastatin 4mg | Changes HDL Particle Number and LDL Particle Number | HDL Particle Number | 2.55 particle number | Standard Deviation 4.19 |
| Pitavastatin 4mg | Changes HDL Particle Number and LDL Particle Number | LDL Particle Number | -768.26 particle number | Standard Deviation 334.01 |
| Rosuvastatin 5 mg | Changes HDL Particle Number and LDL Particle Number | HDL Particle Number | 2.05 particle number | Standard Deviation 5.17 |
| Rosuvastatin 5 mg | Changes HDL Particle Number and LDL Particle Number | LDL Particle Number | -626.61 particle number | Standard Deviation 341.28 |
Secondary
Changes in HDL and LDL Size
Change in levels will be measured by difference in levels at 12 weeks
Time frame: Change from Baseline to 12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin 20mg | Changes in HDL and LDL Size | LDL Size | -0.02 nanometre (nm) | Standard Deviation 0.44 |
| Atorvastatin 20mg | Changes in HDL and LDL Size | HDL Size | 0.23 nanometre (nm) | Standard Deviation 0.27 |
| Pitavastatin 4mg | Changes in HDL and LDL Size | HDL Size | 0.23 nanometre (nm) | Standard Deviation 0.26 |
| Pitavastatin 4mg | Changes in HDL and LDL Size | LDL Size | -0.11 nanometre (nm) | Standard Deviation 0.43 |
| Rosuvastatin 5 mg | Changes in HDL and LDL Size | HDL Size | 0.12 nanometre (nm) | Standard Deviation 0.32 |
| Rosuvastatin 5 mg | Changes in HDL and LDL Size | LDL Size | -0.09 nanometre (nm) | Standard Deviation 0.41 |
Secondary
Changes in Major Lipid Parameters - VLDL Size
Change in levels will be measured by difference in levels at 12 weeks. Measure based on VLDL size.
Time frame: Change from Baseline to 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 20mg | Changes in Major Lipid Parameters - VLDL Size | 0.68 nanometre (nm) | Standard Deviation 5.63 |
| Pitavastatin 4mg | Changes in Major Lipid Parameters - VLDL Size | 0.81 nanometre (nm) | Standard Deviation 5.84 |
| Rosuvastatin 5 mg | Changes in Major Lipid Parameters - VLDL Size | 3.17 nanometre (nm) | Standard Deviation 6.25 |
Secondary
Changes to Glucose Metabolism - Fructosamine
Change in levels will be measured by levels at 12 weeks minus levels at baseline. Changes measured based in fructosamine.
Time frame: Change from Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 20mg | Changes to Glucose Metabolism - Fructosamine | 1.91 µmol | Standard Deviation 17.16 |
| Pitavastatin 4mg | Changes to Glucose Metabolism - Fructosamine | -1.17 µmol | Standard Deviation 13.74 |
| Rosuvastatin 5 mg | Changes to Glucose Metabolism - Fructosamine | -3.07 µmol | Standard Deviation 14.77 |
Secondary
Changes to Glucose Metabolism - HbA1c and Insulin
Change in levels will be measured by levels at 12 weeks minus levels at baseline. Changes measured based in HbA1c, and insulin.
Time frame: Change from Baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin 20mg | Changes to Glucose Metabolism - HbA1c and Insulin | HbA1c | 0.00 percentage change from baseline measure | Standard Deviation 0.03 |
| Atorvastatin 20mg | Changes to Glucose Metabolism - HbA1c and Insulin | Insulin | 0.16 percentage change from baseline measure | Standard Deviation 0.47 |
| Pitavastatin 4mg | Changes to Glucose Metabolism - HbA1c and Insulin | HbA1c | 0.00 percentage change from baseline measure | Standard Deviation 0.04 |
| Pitavastatin 4mg | Changes to Glucose Metabolism - HbA1c and Insulin | Insulin | 0.01 percentage change from baseline measure | Standard Deviation 0.43 |
| Rosuvastatin 5 mg | Changes to Glucose Metabolism - HbA1c and Insulin | HbA1c | 0.00 percentage change from baseline measure | Standard Deviation 0.04 |
| Rosuvastatin 5 mg | Changes to Glucose Metabolism - HbA1c and Insulin | Insulin | 0.17 percentage change from baseline measure | Standard Deviation 0.38 |