Hypercholesterolemia With Concomitant Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to compare the effect of rosuvastatin and atorvastatin on lipid lowering effect and glucose metabolism in hypercholesterolemia patients with diabetes mellitus.
Interventions
DRUGAtorvastatin
Atorvastatin 10 mg (atorvastatin 10 mg tablet x 1 or atorvastatin 5 mg tablet x 2), orally,once daily for 12 months. (When not reach the LDL-C level of target in the Japan Atherosclerosis Society \[JAS\] Guidelines \[GL\] after 3 months, had the atorvastatin \[ATV\] dose of 20 mg.)
DRUGRosuvastatin
Rosuvastatin 5 mg (rosuvastatin 5 mg tablet x1 or rosuvastatin 2.5 mg tablet x 2), orally, once daily for 12 months. (When not reach the LDL-C level of target in JAS GL after 3 months, had the rosuvastatin \[RSV\] dose of 10 mg.)
Sponsors
Listen Trial Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Hypercholesterolemia patients • Patients who have not achieved the target control levels of LDL-C in the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2007 2. Type 2 diabetes patients * Patients diagnosed with type 2 diabetes and receiving diet therapy, exercise therapy, or medication * Patients who received constant therapy for three months before registration and have no plan for therapy change * Patients with kept HbA1c level (Japan Diabetes Society \[JDS\] level) of less than 7.0% (or, National Glycohemoglobin Standardization Program \[NGSP\] level of less than 7.4%) within three months before registration * Patients receiving or not receiving medication at present 3. Patients giving voluntary written consent to participate in the study 4. Male or female patients at 20 years or older
Exclusion criteria
1. Patients who administered rosuvastatin, atorvastatin or ezetimibe within three month at the registration 2. Patients with severe hypertension (systolic blood pressure \[SBP\] ≥ 180 mmHg or diastolic blood pressure \[DBP\] ≥ 110 mmHg) 3. Patients with type 1 diabetes 4. Patients judged to have familial hypercholesterolemia 5. Patients with a serum triglyceride level of ≥ 400 mg/dL 6. Patients who had the onset of cardiovascular or cerebrovascular disease within three months 7. Patients with serious heart failure (NYHA classification III - IV) 8. Patients with a history of hypersensitivity to statins 9. Patients with a history of drug-induced myopathy 10. Patients with severe complication of diabetes 11. Patients receiving insulin 12. Patients with serious liver or kidney disease 13. Patients with serious concurrent disease such as malignancy, or patients with severely limited lifespan 14. Patients who are or may be pregnant 15. Patients judged by the investigators to be ineligible for participation in the study for any other reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level | Baseline, and 12 months after administration |
| Change in HbA1c Level | Baseline, 12 months after administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in 1,5-AG Level | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa |
| Change in HbA1c Level | Baseline, 3, 6 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | — |
| Percent Change in Blood Glucose Level (Fasting) | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | — |
| Change in Blood Glucose Level (Fasting) | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | — |
| Percent Change in Insulin Level | Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa. |
| Change From Baseline in Insulin Level | Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa |
| Occurrence of Deterioration of Diabetic Treatment Status | Baseline, 12 months after administration | Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of \> 0.5%. |
| Frequency of Serious Adverse Events (SAE) | Up to 12 months | — |
| Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment | — |
| Percent Change in Non-HDL-C Level | Baseline, 3 and 6 months after administration, the end of starting dose and the end of study treatment | — |
| Percent Changes in Lipids and Inflammatory Marker (Hs-CRP) and Their Correlation | Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment | Correlation between percent changes in lipids (LDL-C, HDL-C, non-HDL-C, TG, non-HDL-C/HDL-C ratio, LDL-C/HDL-C ratio, TC and FFA) and inflammatory marker (hs-CRP) |
| Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | 3 months after administration, the end of starting dose and the end of study treatment | Percentage of participants achieving the target LDL-C levels \<100 mg/dL for participants with history of coronary artery diseases (CAD) and \<120 mg/dL for participants without history of CAD are presented. |
| Change From Baseline in 1,5-AG Level | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa |
| Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease) | From the start of the treatment to the end of study treatment | — |
| Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Baseline, 3, 6, 12 months after administration | Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of \> 0.5%. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Administration Group Atorvastatin: Atorvastatin 10 mg (atorvastatin 10 mg tablet x 1 or atorvastatin 5 mg tablet x 2), orally,once daily for 12 months.
(When not reach the LDL-C level of target in JAS GL after 3 months, had the ATV dose of 20 mg.) | 504 |
| Rosuvastatin Administration Group Rosuvastatin: Rosuvastatin 5 mg (rosuvastatin 5 mg tablet x1 or rosuvastatin 2.5 mg tablet x 2), orally, once daily for 12 months.
(When not reach the LDL-C level of target in JAS GL after 3 months, had the RSV dose of 10 mg.) | 514 |
| Total | 1,018 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administered prohibit prior medication | 1 | 0 |
| Overall Study | Not performed pre-dose examination | 1 | 2 |
| Overall Study | Physician Decision | 4 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 7 |
Baseline characteristics
| Characteristic | Total | Atorvastatin Administration Group | Rosuvastatin Administration Group |
|---|---|---|---|
| 1,5-anhydro-D-glucitol (1,5-AG) | 15.40 μg/mL STANDARD_DEVIATION 8.01 | 15.40 μg/mL STANDARD_DEVIATION 7.91 | 15.39 μg/mL STANDARD_DEVIATION 8.1 |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 11.1 | 66.6 years STANDARD_DEVIATION 10.6 | 66.3 years STANDARD_DEVIATION 11.6 |
| Angina pectoris With events | 62 participants | 31 participants | 31 participants |
| Angina pectoris Without events | 956 participants | 473 participants | 483 participants |
| Blood glucose | 118.9 mg/dL STANDARD_DEVIATION 29.2 | 118.8 mg/dL STANDARD_DEVIATION 27 | 119.1 mg/dL STANDARD_DEVIATION 31.2 |
| Cardiac arrhythmias With events | 57 participants | 31 participants | 26 participants |
| Cardiac arrhythmias Without events | 961 participants | 473 participants | 488 participants |
| Cardiovascular and Cerebrovascular events before entry With events | 206 participants | 103 participants | 103 participants |
| Cardiovascular and Cerebrovascular events before entry Without events | 812 participants | 401 participants | 411 participants |
| Cerebral haemorrhage With events | 9 participants | 3 participants | 6 participants |
| Cerebral haemorrhage Without events | 1009 participants | 501 participants | 508 participants |
| Cerebral infarction With events | 51 participants | 21 participants | 30 participants |
| Cerebral infarction Without events | 967 participants | 483 participants | 484 participants |
| Complications related to diabetes With diabetic complications | 116 participants | 49 participants | 67 participants |
| Complications related to diabetes Without diabetic complications | 902 participants | 455 participants | 447 participants |
| Diabetic foot With diabetic foot | 1 participants | 0 participants | 1 participants |
| Diabetic foot Without diabetic foot | 1017 participants | 504 participants | 513 participants |
| Diabetic nephropathy With diabetic nephropathy | 34 participants | 13 participants | 21 participants |
| Diabetic nephropathy Without diabetic nephropathy | 984 participants | 491 participants | 493 participants |
| Diabetic neuropathy With diabetic neuropathy | 46 participants | 23 participants | 23 participants |
| Diabetic neuropathy Without diabetic neuropathy | 972 participants | 481 participants | 491 participants |
| Diabetic retinopathy With diabetic retinopathy | 13 participants | 4 participants | 9 participants |
| Diabetic retinopathy Without diabetic retinopathy | 1005 participants | 500 participants | 505 participants |
| Free fatty acids (FFA) | 0.584 mEq/L STANDARD_DEVIATION 0.298 | 0.585 mEq/L STANDARD_DEVIATION 0.297 | 0.584 mEq/L STANDARD_DEVIATION 0.299 |
| HbA1c | 6.39 % (NGSP value) STANDARD_DEVIATION 0.63 | 6.38 % (NGSP value) STANDARD_DEVIATION 0.59 | 6.40 % (NGSP value) STANDARD_DEVIATION 0.66 |
| HDL-C | 54.9 mg/dL STANDARD_DEVIATION 14.1 | 55.8 mg/dL STANDARD_DEVIATION 14.6 | 54.1 mg/dL STANDARD_DEVIATION 13.6 |
| Heart failure With events | 18 participants | 10 participants | 8 participants |
| Heart failure Without events | 1000 participants | 494 participants | 506 participants |
| Hypertension With hypertension | 645 participants | 307 participants | 338 participants |
| Hypertension Without hypertension | 373 participants | 197 participants | 176 participants |
| Insulin | 11.77 μU/mL STANDARD_DEVIATION 19.39 | 10.95 μU/mL STANDARD_DEVIATION 18.66 | 12.57 μU/mL STANDARD_DEVIATION 20.07 |
| LDL-C/HDL-C ratio | 2.69 ratio STANDARD_DEVIATION 0.86 | 2.66 ratio STANDARD_DEVIATION 0.81 | 2.73 ratio STANDARD_DEVIATION 0.91 |
| Low-density lipoprotein cholesterol (LDL-C) | 139.4 mg/dL STANDARD_DEVIATION 30 | 139.6 mg/dL STANDARD_DEVIATION 27.9 | 139.2 mg/dL STANDARD_DEVIATION 31.9 |
| Myocardial infarction With events | 14 participants | 7 participants | 7 participants |
| Myocardial infarction Without events | 1004 participants | 497 participants | 507 participants |
| Non-HDL-C/HDL-C ratio | 3.30 ratio STANDARD_DEVIATION 1.2 | 3.25 ratio STANDARD_DEVIATION 1.07 | 3.36 ratio STANDARD_DEVIATION 1.31 |
| Non-high-density lipoprotein cholesterol (HDL-C) | 168.9 mg/dL STANDARD_DEVIATION 33.3 | 169.0 mg/dL STANDARD_DEVIATION 30.6 | 168.9 mg/dL STANDARD_DEVIATION 35.8 |
| Revascularization With events | 12 participants | 3 participants | 9 participants |
| Revascularization Without events | 1006 participants | 501 participants | 505 participants |
| Sex/Gender, Customized Male | 1018 participants | 504 participants | 514 participants |
| Statin administration before entry Administered | 241 participants | 120 participants | 121 participants |
| Statin administration before entry Not administered | 777 participants | 384 participants | 393 participants |
| Total cholesterol (TC) | 223.9 mg/dL STANDARD_DEVIATION 34 | 224.8 mg/dL STANDARD_DEVIATION 31.8 | 223.0 mg/dL STANDARD_DEVIATION 36 |
| Transient ischaemic attack With events | 9 participants | 5 participants | 4 participants |
| Transient ischaemic attack Without events | 1009 participants | 499 participants | 510 participants |
| Triglyceride (TG) | 152.1 mg/dL STANDARD_DEVIATION 115.8 | 149.6 mg/dL STANDARD_DEVIATION 89.1 | 154.5 mg/dL STANDARD_DEVIATION 137.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 87 / 506 | 88 / 516 |
| serious Total, serious adverse events | 14 / 506 | 19 / 516 |
Outcome results
Primary
Change in HbA1c Level
Time frame: Baseline, 12 months after administration
Population: Participants in FAS except the ones who had no HbA1c data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin Administration Group | Change in HbA1c Level | 0.120 Amount of change (%) | Standard Deviation 0.65 |
| Rosuvastatin Administration Group | Change in HbA1c Level | 0.10 Amount of change (%) | Standard Deviation 0.67 |
Primary
Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level
Time frame: Baseline, and 12 months after administration
Population: Participants in full analysis set (FAS) except the ones who had no HDL-C data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin Administration Group | Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level | -31.3 Percent change | Standard Deviation 19.1 |
| Rosuvastatin Administration Group | Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level | -32.8 Percent change | Standard Deviation 18.1 |
Secondary
Change From Baseline in 1,5-AG Level
An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 3 months | -0.51 μg/mL | Standard Deviation 3.48 |
| Atorvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 6 months | -1.28 μg/mL | Standard Deviation 4.23 |
| Atorvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 12 months | -0.88 μg/mL | Standard Deviation 4.33 |
| Atorvastatin Administration Group | Change From Baseline in 1,5-AG Level | Baseline 1,5-AG level | 15.40 μg/mL | Standard Deviation 7.91 |
| Rosuvastatin Administration Group | Change From Baseline in 1,5-AG Level | Baseline 1,5-AG level | 15.39 μg/mL | Standard Deviation 8.1 |
| Rosuvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 3 months | -0.21 μg/mL | Standard Deviation 3.77 |
| Rosuvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 12 months | -1.09 μg/mL | Standard Deviation 4.66 |
| Rosuvastatin Administration Group | Change From Baseline in 1,5-AG Level | At 6 months | -0.94 μg/mL | Standard Deviation 4.64 |
Secondary
Change From Baseline in Insulin Level
An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Population: Full analysis set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Change From Baseline in Insulin Level | At 3 months | -0.10 μU/mL | Standard Deviation 20.26 |
| Atorvastatin Administration Group | Change From Baseline in Insulin Level | At 6 months | 0.66 μU/mL | Standard Deviation 18.63 |
| Atorvastatin Administration Group | Change From Baseline in Insulin Level | At 12 months | -1.50 μU/mL | Standard Deviation 18.69 |
| Atorvastatin Administration Group | Change From Baseline in Insulin Level | Baseline Insulin level | 10.95 μU/mL | Standard Deviation 18.66 |
| Rosuvastatin Administration Group | Change From Baseline in Insulin Level | Baseline Insulin level | 12.57 μU/mL | Standard Deviation 20.07 |
| Rosuvastatin Administration Group | Change From Baseline in Insulin Level | At 3 months | -0.54 μU/mL | Standard Deviation 18.56 |
| Rosuvastatin Administration Group | Change From Baseline in Insulin Level | At 12 months | -2.91 μU/mL | Standard Deviation 19.02 |
| Rosuvastatin Administration Group | Change From Baseline in Insulin Level | At 6 months | -0.44 μU/mL | Standard Deviation 19.86 |
Secondary
Change in Blood Glucose Level (Fasting)
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 3 months | 2.6 mg/dL | Standard Deviation 24.5 |
| Atorvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 6 months | 6.8 mg/dL | Standard Deviation 30.2 |
| Atorvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 12 months | 3.6 mg/dL | Standard Deviation 30.7 |
| Rosuvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 3 months | 0.1 mg/dL | Standard Deviation 31.2 |
| Rosuvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 6 months | 4.3 mg/dL | Standard Deviation 31.5 |
| Rosuvastatin Administration Group | Change in Blood Glucose Level (Fasting) | At 12 months | 1.5 mg/dL | Standard Deviation 35 |
Secondary
Change in HbA1c Level
Time frame: Baseline, 3, 6 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Population: Full analysis set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Change in HbA1c Level | At 3 months | 0.05 Amount of change (%) | Standard Deviation 0.42 |
| Atorvastatin Administration Group | Change in HbA1c Level | At 6 months | 0.13 Amount of change (%) | Standard Deviation 0.57 |
| Rosuvastatin Administration Group | Change in HbA1c Level | At 3 months | 0.00 Amount of change (%) | Standard Deviation 0.5 |
| Rosuvastatin Administration Group | Change in HbA1c Level | At 6 months | 0.12 Amount of change (%) | Standard Deviation 0.65 |
Secondary
Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease)
Time frame: From the start of the treatment to the end of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin Administration Group | Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease) | 5 Number of patients with any events |
| Rosuvastatin Administration Group | Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease) | 9 Number of patients with any events |
Secondary
Frequency of Serious Adverse Events (SAE)
Time frame: Up to 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin Administration Group | Frequency of Serious Adverse Events (SAE) | 14 Number of patients with SAE |
| Rosuvastatin Administration Group | Frequency of Serious Adverse Events (SAE) | 19 Number of patients with SAE |
Secondary
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status
Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of \> 0.5%.
Time frame: Baseline, 3, 6, 12 months after administration
Population: Full analysis set - All participants who received at least 1 dose of open-label study drug except the ones who had no HbA1c or non-HDL-C data or a protocol deviation of the administration of study drugs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 6-12 months | 32 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 3-6 months | 5 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 3-6 months | 12 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 6-12 months | 8 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 0-3 months | 6 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | No deterioration | 421 participants |
| Atorvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 0-3 months | 20 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | No deterioration | 453 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 0-3 months | 14 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 3-6 months | 8 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification: 6-12 months | 23 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 0-3 months | 5 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 3-6 months | 5 participants |
| Rosuvastatin Administration Group | Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Other: 6-12 months | 6 participants |
Secondary
Occurrence of Deterioration of Diabetic Treatment Status
Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of \> 0.5%.
Time frame: Baseline, 12 months after administration
Population: Full analysis set - All participants who received at least 1 dose of open-label study drug except the ones who had no HbA1c or non-HDL-C data or a protocol deviation of the administration of study drugs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin Administration Group | Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification | 64 Participants |
| Atorvastatin Administration Group | Occurrence of Deterioration of Diabetic Treatment Status | Deterioration in HbA1c of > 0.5% | 177 Participants |
| Rosuvastatin Administration Group | Occurrence of Deterioration of Diabetic Treatment Status | Therapy intensification | 45 Participants |
| Rosuvastatin Administration Group | Occurrence of Deterioration of Diabetic Treatment Status | Deterioration in HbA1c of > 0.5% | 162 Participants |
Secondary
Percent Change in 1,5-AG Level
An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
Population: Participants in FAS except the ones who had no 1,5-AG data at 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Percent Change in 1,5-AG Level | At 3 months | -1.6 Percent change | Standard Deviation 30.8 |
| Atorvastatin Administration Group | Percent Change in 1,5-AG Level | At 6 months | -6.5 Percent change | Standard Deviation 35.8 |
| Atorvastatin Administration Group | Percent Change in 1,5-AG Level | At 12 months | -3.8 Percent change | Standard Deviation 35.1 |
| Rosuvastatin Administration Group | Percent Change in 1,5-AG Level | At 3 months | 5.5 Percent change | Standard Deviation 72.6 |
| Rosuvastatin Administration Group | Percent Change in 1,5-AG Level | At 6 months | 2.6 Percent change | Standard Deviation 83.7 |
| Rosuvastatin Administration Group | Percent Change in 1,5-AG Level | At 12 months | 3.5 Percent change | Standard Deviation 98 |
Secondary
Percent Change in Blood Glucose Level (Fasting)
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
Population: Participants in FAS except the ones who had no blood glucose level data at 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 3 months | 3.3 Percent change | Standard Deviation 19.3 |
| Atorvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 6 months | 7.0 Percent change | Standard Deviation 24.1 |
| Atorvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 12 months | 4.6 Percent change | Standard Deviation 24.3 |
| Rosuvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 3 months | 2.7 Percent change | Standard Deviation 25 |
| Rosuvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 6 months | 5.9 Percent change | Standard Deviation 25.7 |
| Rosuvastatin Administration Group | Percent Change in Blood Glucose Level (Fasting) | At 12 months | 3.7 Percent change | Standard Deviation 26.1 |
Secondary
Percent Change in Insulin Level
An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa.
Time frame: Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Population: Full analysis set - All participants who received at least 1 dose of open-label study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Percent Change in Insulin Level | At 3 months | 40.7 Percent change | Standard Deviation 211.2 |
| Atorvastatin Administration Group | Percent Change in Insulin Level | At 6 months | 45.1 Percent change | Standard Deviation 193.9 |
| Atorvastatin Administration Group | Percent Change in Insulin Level | At 12 months | 17.4 Percent change | Standard Deviation 132.9 |
| Rosuvastatin Administration Group | Percent Change in Insulin Level | At 3 months | 31.3 Percent change | Standard Deviation 166.4 |
| Rosuvastatin Administration Group | Percent Change in Insulin Level | At 6 months | 35.5 Percent change | Standard Deviation 142.8 |
| Rosuvastatin Administration Group | Percent Change in Insulin Level | At 12 months | 13.8 Percent change | Standard Deviation 148.1 |
Secondary
Percent Change in Non-HDL-C Level
Time frame: Baseline, 3 and 6 months after administration, the end of starting dose and the end of study treatment
Population: Participants in FAS except the ones who had no non-HDL-C level data at 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Percent Change in Non-HDL-C Level | At 3 months | -33.8 Percent change | Standard Deviation 17.6 |
| Atorvastatin Administration Group | Percent Change in Non-HDL-C Level | At 6 months | -33.2 Percent change | Standard Deviation 16.6 |
| Rosuvastatin Administration Group | Percent Change in Non-HDL-C Level | At 3 months | -35.5 Percent change | Standard Deviation 18.4 |
| Rosuvastatin Administration Group | Percent Change in Non-HDL-C Level | At 6 months | -33.5 Percent change | Standard Deviation 18.8 |
Secondary
Percent Changes in Lipids and Inflammatory Marker (Hs-CRP) and Their Correlation
Correlation between percent changes in lipids (LDL-C, HDL-C, non-HDL-C, TG, non-HDL-C/HDL-C ratio, LDL-C/HDL-C ratio, TC and FFA) and inflammatory marker (hs-CRP)
Time frame: Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment
Secondary
Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA)
Time frame: Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment
Population: Participants in FAS except the ones who had no lipids level data at 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 3 months | -36.6 Percent change | Standard Deviation 19.2 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 6 months | -35.6 Percent change | Standard Deviation 19.4 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 12 months | -33.2 Percent change | Standard Deviation 21.5 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 3 months | 4.1 Percent change | Standard Deviation 14.3 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 6 months | 7.1 Percent change | Standard Deviation 15.1 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 12 months | 4.9 Percent change | Standard Deviation 14.7 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 3 months | -24.7 Percent change | Standard Deviation 13.3 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 6 months | -23.5 Percent change | Standard Deviation 13 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 12 months | -22.7 Percent change | Standard Deviation 14.3 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG at 3 months | -12.7 Percent change | Standard Deviation 38 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG: at 6 months | -12.4 Percent change | Standard Deviation 45.9 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG: at 12 months | -12.6 Percent change | Standard Deviation 62.2 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 3 months | -34.8 Percent change | Standard Deviation 22.6 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 6 months | -36.1 Percent change | Standard Deviation 19.4 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 12 months | -33.1 Percent change | Standard Deviation 22.7 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 3 months | 19.9 Percent change | Standard Deviation 87.8 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 6 months | 13.8 Percent change | Standard Deviation 80.5 |
| Atorvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 12 months | 37.2 Percent change | Standard Deviation 125.3 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 6 months | -37.2 Percent change | Standard Deviation 20.8 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 3 months | -39.2 Percent change | Standard Deviation 21.3 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG at 3 months | -11.0 Percent change | Standard Deviation 42.2 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 6 months | -36.4 Percent change | Standard Deviation 21.8 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 12 months | 34.8 Percent change | Standard Deviation 111 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | LDL-C: at 12 months | -34.7 Percent change | Standard Deviation 21 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG: at 6 months | -11.9 Percent change | Standard Deviation 38 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 3 months | 5.6 Percent change | Standard Deviation 13.9 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 12 months | -36.0 Percent change | Standard Deviation 20.7 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 6 months | 8.2 Percent change | Standard Deviation 15.2 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TG: at 12 months | -15.9 Percent change | Standard Deviation 35.4 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | HDL-C: at 12 months | 7.7 Percent change | Standard Deviation 15.9 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 6 months | 15.9 Percent change | Standard Deviation 88.9 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 3 months | -25.9 Percent change | Standard Deviation 14.3 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | Non-HDL-C/HDL-C ratio: at 3 months | -37.7 Percent change | Standard Deviation 20.2 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 6 months | -23.8 Percent change | Standard Deviation 14.9 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | FFA: at 3 months | 25.9 Percent change | Standard Deviation 111.3 |
| Rosuvastatin Administration Group | Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) | TC: at 12 months | -23.5 Percent change | Standard Deviation 14 |
Secondary
Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007
Percentage of participants achieving the target LDL-C levels \<100 mg/dL for participants with history of coronary artery diseases (CAD) and \<120 mg/dL for participants without history of CAD are presented.
Time frame: 3 months after administration, the end of starting dose and the end of study treatment
Population: Full analysis set except participants who have reached the target LDL-C level specified at the treatment start
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin Administration Group | Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | At 3 months | 89.0 Percentage of participants |
| Atorvastatin Administration Group | Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | At the end of study treatment | 86.3 Percentage of participants |
| Rosuvastatin Administration Group | Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | At 3 months | 89.9 Percentage of participants |
| Rosuvastatin Administration Group | Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | At the end of study treatment | 87.5 Percentage of participants |