Trial Outcomes & Findings for LIpid Lowering With Highly Potent Statins in Hyperlipidaemia With Type 2 Diabetes patiENts (NCT NCT01544309)

NCT ID: NCT01544309

Last Updated: 2015-03-17

Results Overview

Recruitment status

COMPLETED

Study phase

Target enrollment

1049 participants

Primary outcome timeframe

Baseline, and 12 months after administration

Results posted on

2015-03-17

Participant Flow

Participant milestones

Participant milestones
Measure	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 the Japan Atherosclerosis Society (JAS) Guidelines (GL) after 3 months, had the atorvastatin \[ATV\] dose of 20 mg.)	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 rosuvastatin \[RSV\] dose of 10 mg.)
Overall Study STARTED	524	525
Overall Study COMPLETED	504	514
Overall Study NOT COMPLETED	20	11

Reasons for withdrawal

Reasons for withdrawal
Measure	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 the Japan Atherosclerosis Society (JAS) Guidelines (GL) after 3 months, had the atorvastatin \[ATV\] dose of 20 mg.)	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 rosuvastatin \[RSV\] dose of 10 mg.)
Overall Study Withdrawal by Subject	12	7
Overall Study Protocol Violation	2	1
Overall Study Physician Decision	4	1
Overall Study Not performed pre-dose examination	1	2
Overall Study Administered prohibit prior medication	1	0

Baseline Characteristics

LIpid Lowering With Highly Potent Statins in Hyperlipidaemia With Type 2 Diabetes patiENts

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)	Total n=1018 Participants Total of all reporting groups
Age, Continuous	66.6 years STANDARD_DEVIATION 10.6 • n=5 Participants	66.3 years STANDARD_DEVIATION 11.6 • n=7 Participants	66.4 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex/Gender, Customized Male	504 participants n=5 Participants	514 participants n=7 Participants	1018 participants n=5 Participants
Statin administration before entry Administered	120 participants n=5 Participants	121 participants n=7 Participants	241 participants n=5 Participants
Statin administration before entry Not administered	384 participants n=5 Participants	393 participants n=7 Participants	777 participants n=5 Participants
Cardiovascular and Cerebrovascular events before entry With events	103 participants n=5 Participants	103 participants n=7 Participants	206 participants n=5 Participants
Cardiovascular and Cerebrovascular events before entry Without events	401 participants n=5 Participants	411 participants n=7 Participants	812 participants n=5 Participants
Myocardial infarction With events	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Myocardial infarction Without events	497 participants n=5 Participants	507 participants n=7 Participants	1004 participants n=5 Participants
Angina pectoris With events	31 participants n=5 Participants	31 participants n=7 Participants	62 participants n=5 Participants
Angina pectoris Without events	473 participants n=5 Participants	483 participants n=7 Participants	956 participants n=5 Participants
Heart failure With events	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Heart failure Without events	494 participants n=5 Participants	506 participants n=7 Participants	1000 participants n=5 Participants
Revascularization With events	3 participants n=5 Participants	9 participants n=7 Participants	12 participants n=5 Participants
Revascularization Without events	501 participants n=5 Participants	505 participants n=7 Participants	1006 participants n=5 Participants
Cardiac arrhythmias With events	31 participants n=5 Participants	26 participants n=7 Participants	57 participants n=5 Participants
Cardiac arrhythmias Without events	473 participants n=5 Participants	488 participants n=7 Participants	961 participants n=5 Participants
Cerebral haemorrhage With events	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Cerebral haemorrhage Without events	501 participants n=5 Participants	508 participants n=7 Participants	1009 participants n=5 Participants
Cerebral infarction With events	21 participants n=5 Participants	30 participants n=7 Participants	51 participants n=5 Participants
Cerebral infarction Without events	483 participants n=5 Participants	484 participants n=7 Participants	967 participants n=5 Participants
Transient ischaemic attack With events	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Transient ischaemic attack Without events	499 participants n=5 Participants	510 participants n=7 Participants	1009 participants n=5 Participants
Complications related to diabetes With diabetic complications	49 participants n=5 Participants	67 participants n=7 Participants	116 participants n=5 Participants
Complications related to diabetes Without diabetic complications	455 participants n=5 Participants	447 participants n=7 Participants	902 participants n=5 Participants
Diabetic retinopathy With diabetic retinopathy	4 participants n=5 Participants	9 participants n=7 Participants	13 participants n=5 Participants
Diabetic retinopathy Without diabetic retinopathy	500 participants n=5 Participants	505 participants n=7 Participants	1005 participants n=5 Participants
Diabetic nephropathy With diabetic nephropathy	13 participants n=5 Participants	21 participants n=7 Participants	34 participants n=5 Participants
Diabetic nephropathy Without diabetic nephropathy	491 participants n=5 Participants	493 participants n=7 Participants	984 participants n=5 Participants
Diabetic neuropathy With diabetic neuropathy	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants
Diabetic neuropathy Without diabetic neuropathy	481 participants n=5 Participants	491 participants n=7 Participants	972 participants n=5 Participants
Diabetic foot With diabetic foot	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Diabetic foot Without diabetic foot	504 participants n=5 Participants	513 participants n=7 Participants	1017 participants n=5 Participants
Hypertension With hypertension	307 participants n=5 Participants	338 participants n=7 Participants	645 participants n=5 Participants
Hypertension Without hypertension	197 participants n=5 Participants	176 participants n=7 Participants	373 participants n=5 Participants
Non-high-density lipoprotein cholesterol (HDL-C)	169.0 mg/dL STANDARD_DEVIATION 30.6 • n=5 Participants	168.9 mg/dL STANDARD_DEVIATION 35.8 • n=7 Participants	168.9 mg/dL STANDARD_DEVIATION 33.3 • n=5 Participants
Low-density lipoprotein cholesterol (LDL-C)	139.6 mg/dL STANDARD_DEVIATION 27.9 • n=5 Participants	139.2 mg/dL STANDARD_DEVIATION 31.9 • n=7 Participants	139.4 mg/dL STANDARD_DEVIATION 30.0 • n=5 Participants
HDL-C	55.8 mg/dL STANDARD_DEVIATION 14.6 • n=5 Participants	54.1 mg/dL STANDARD_DEVIATION 13.6 • n=7 Participants	54.9 mg/dL STANDARD_DEVIATION 14.1 • n=5 Participants
Total cholesterol (TC)	224.8 mg/dL STANDARD_DEVIATION 31.8 • n=5 Participants	223.0 mg/dL STANDARD_DEVIATION 36.0 • n=7 Participants	223.9 mg/dL STANDARD_DEVIATION 34.0 • n=5 Participants
Triglyceride (TG)	149.6 mg/dL STANDARD_DEVIATION 89.1 • n=5 Participants	154.5 mg/dL STANDARD_DEVIATION 137.1 • n=7 Participants	152.1 mg/dL STANDARD_DEVIATION 115.8 • n=5 Participants
Non-HDL-C/HDL-C ratio	3.25 ratio STANDARD_DEVIATION 1.07 • n=5 Participants	3.36 ratio STANDARD_DEVIATION 1.31 • n=7 Participants	3.30 ratio STANDARD_DEVIATION 1.20 • n=5 Participants
LDL-C/HDL-C ratio	2.66 ratio STANDARD_DEVIATION 0.81 • n=5 Participants	2.73 ratio STANDARD_DEVIATION 0.91 • n=7 Participants	2.69 ratio STANDARD_DEVIATION 0.86 • n=5 Participants
Free fatty acids (FFA)	0.585 mEq/L STANDARD_DEVIATION 0.297 • n=5 Participants	0.584 mEq/L STANDARD_DEVIATION 0.299 • n=7 Participants	0.584 mEq/L STANDARD_DEVIATION 0.298 • n=5 Participants
HbA1c	6.38 % (NGSP value) STANDARD_DEVIATION 0.59 • n=5 Participants	6.40 % (NGSP value) STANDARD_DEVIATION 0.66 • n=7 Participants	6.39 % (NGSP value) STANDARD_DEVIATION 0.63 • n=5 Participants
Blood glucose	118.8 mg/dL STANDARD_DEVIATION 27.0 • n=5 Participants	119.1 mg/dL STANDARD_DEVIATION 31.2 • n=7 Participants	118.9 mg/dL STANDARD_DEVIATION 29.2 • n=5 Participants
Insulin	10.95 μU/mL STANDARD_DEVIATION 18.66 • n=5 Participants	12.57 μU/mL STANDARD_DEVIATION 20.07 • n=7 Participants	11.77 μU/mL STANDARD_DEVIATION 19.39 • n=5 Participants
1,5-anhydro-D-glucitol (1,5-AG)	15.40 μg/mL STANDARD_DEVIATION 7.91 • n=5 Participants	15.39 μg/mL STANDARD_DEVIATION 8.10 • n=7 Participants	15.40 μg/mL STANDARD_DEVIATION 8.01 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=472 Participants 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.)	Rosuvastatin Administration Group n=468 Participants 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.)
Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level	-31.3 Percent change Standard Deviation 19.1	-32.8 Percent change Standard Deviation 18.1

PRIMARY outcome

Timeframe: Baseline, 12 months after administration

Population: Participants in FAS except the ones who had no HbA1c data at 12 months.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=472 Participants 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.)	Rosuvastatin Administration Group n=468 Participants 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.)
Change in HbA1c Level	0.120 Amount of change (%) Standard Deviation 0.65	0.10 Amount of change (%) Standard Deviation 0.67

SECONDARY outcome

Timeframe: 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.

"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%.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Occurrence of Deterioration of Diabetic Treatment Status Therapy intensification	64 Participants	45 Participants
Occurrence of Deterioration of Diabetic Treatment Status Deterioration in HbA1c of > 0.5%	177 Participants	162 Participants

SECONDARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Therapy intensification: 0-3 months	20 participants	14 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Therapy intensification: 3-6 months	12 participants	8 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Therapy intensification: 6-12 months	32 participants	23 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Other: 0-3 months	6 participants	5 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Other: 3-6 months	5 participants	5 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status Other: 6-12 months	8 participants	6 participants
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status No deterioration	421 participants	453 participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Percent Change in 1,5-AG Level At 3 months	-1.6 Percent change Standard Deviation 30.8	5.5 Percent change Standard Deviation 72.6
Percent Change in 1,5-AG Level At 6 months	-6.5 Percent change Standard Deviation 35.8	2.6 Percent change Standard Deviation 83.7
Percent Change in 1,5-AG Level At 12 months	-3.8 Percent change Standard Deviation 35.1	3.5 Percent change Standard Deviation 98.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Change in HbA1c Level At 3 months	0.05 Amount of change (%) Standard Deviation 0.42	0.00 Amount of change (%) Standard Deviation 0.50
Change in HbA1c Level At 6 months	0.13 Amount of change (%) Standard Deviation 0.57	0.12 Amount of change (%) Standard Deviation 0.65

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Percent Change in Blood Glucose Level (Fasting) At 6 months	7.0 Percent change Standard Deviation 24.1	5.9 Percent change Standard Deviation 25.7
Percent Change in Blood Glucose Level (Fasting) At 3 months	3.3 Percent change Standard Deviation 19.3	2.7 Percent change Standard Deviation 25.0
Percent Change in Blood Glucose Level (Fasting) At 12 months	4.6 Percent change Standard Deviation 24.3	3.7 Percent change Standard Deviation 26.1

SECONDARY outcome

Timeframe: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Change in Blood Glucose Level (Fasting) At 3 months	2.6 mg/dL Standard Deviation 24.5	0.1 mg/dL Standard Deviation 31.2
Change in Blood Glucose Level (Fasting) At 6 months	6.8 mg/dL Standard Deviation 30.2	4.3 mg/dL Standard Deviation 31.5
Change in Blood Glucose Level (Fasting) At 12 months	3.6 mg/dL Standard Deviation 30.7	1.5 mg/dL Standard Deviation 35.0

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Percent Change in Insulin Level At 3 months	40.7 Percent change Standard Deviation 211.2	31.3 Percent change Standard Deviation 166.4
Percent Change in Insulin Level At 6 months	45.1 Percent change Standard Deviation 193.9	35.5 Percent change Standard Deviation 142.8
Percent Change in Insulin Level At 12 months	17.4 Percent change Standard Deviation 132.9	13.8 Percent change Standard Deviation 148.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Change From Baseline in Insulin Level At 3 months	-0.10 μU/mL Standard Deviation 20.26	-0.54 μU/mL Standard Deviation 18.56
Change From Baseline in Insulin Level At 6 months	0.66 μU/mL Standard Deviation 18.63	-0.44 μU/mL Standard Deviation 19.86
Change From Baseline in Insulin Level At 12 months	-1.50 μU/mL Standard Deviation 18.69	-2.91 μU/mL Standard Deviation 19.02
Change From Baseline in Insulin Level Baseline Insulin level	10.95 μU/mL Standard Deviation 18.66	12.57 μU/mL Standard Deviation 20.07

SECONDARY outcome

Timeframe: From the start of the treatment to the end of study treatment

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease)	5 Number of patients with any events	9 Number of patients with any events

SECONDARY outcome

Timeframe: Up to 12 months

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=506 Participants 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.)	Rosuvastatin Administration Group n=516 Participants 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.)
Frequency of Serious Adverse Events (SAE)	14 Number of patients with SAE	19 Number of patients with SAE

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
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	15.9 Percent change Standard Deviation 88.9
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	-39.2 Percent change Standard Deviation 21.3
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	-36.4 Percent change Standard Deviation 21.8
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	-34.7 Percent change Standard Deviation 21.0
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	5.6 Percent change Standard Deviation 13.9
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	8.2 Percent change Standard Deviation 15.2
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	7.7 Percent change Standard Deviation 15.9
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	-25.9 Percent change Standard Deviation 14.3
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 13.0	-23.8 Percent change Standard Deviation 14.9
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	-23.5 Percent change Standard Deviation 14.0
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 38.0	-11.0 Percent change Standard Deviation 42.2
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	-11.9 Percent change Standard Deviation 38.0
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	-15.9 Percent change Standard Deviation 35.4
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	-37.7 Percent change Standard Deviation 20.2
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	-37.2 Percent change Standard Deviation 20.8
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	-36.0 Percent change Standard Deviation 20.7
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	25.9 Percent change Standard Deviation 111.3
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	34.8 Percent change Standard Deviation 111.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=504 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Percent Change in Non-HDL-C Level At 3 months	-33.8 Percent change Standard Deviation 17.6	-35.5 Percent change Standard Deviation 18.4
Percent Change in Non-HDL-C Level At 6 months	-33.2 Percent change Standard Deviation 16.6	-33.5 Percent change Standard Deviation 18.8

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=383 Participants 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.)	Rosuvastatin Administration Group n=366 Participants 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.)
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 Interval 85.5 to 92.0	89.9 Percentage of participants Interval 86.3 to 92.8
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 Interval 82.5 to 89.6	87.5 Percentage of participants Interval 83.7 to 90.7

SECONDARY outcome

Timeframe: Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）

Outcome measures

Outcome measures
Measure	Atorvastatin Administration Group n=503 Participants 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.)	Rosuvastatin Administration Group n=514 Participants 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.)
Change From Baseline in 1,5-AG Level At 3 months	-0.51 μg/mL Standard Deviation 3.48	-0.21 μg/mL Standard Deviation 3.77
Change From Baseline in 1,5-AG Level At 6 months	-1.28 μg/mL Standard Deviation 4.23	-0.94 μg/mL Standard Deviation 4.64
Change From Baseline in 1,5-AG Level At 12 months	-0.88 μg/mL Standard Deviation 4.33	-1.09 μg/mL Standard Deviation 4.66
Change From Baseline in 1,5-AG Level Baseline 1,5-AG level	15.40 μg/mL Standard Deviation 7.91	15.39 μg/mL Standard Deviation 8.10

Adverse Events

Atorvastatin Administration Group

Serious events: 14 serious events

Other events: 87 other events

Deaths: 0 deaths

Rosuvastatin Administration Group

Serious events: 19 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Hisao Ogawa, Ph.D; Study Chair

Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University

Phone: + 81 963735175

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Atorvastatin Administration Group n=506 participants at risk 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.)	Rosuvastatin Administration Group n=516 participants at risk 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.)
Infections and infestations Pneumonia	0.20% 1/506 • Number of events 1 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.39% 2/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Infections and infestations Diverticulitis	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Infections and infestations Nocardiosis	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Infections and infestations Keratitis fungal	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Large intestine carcinoma	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiosarcoma	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholesteatoma	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Psychiatric disorders Completed suicide	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Psychiatric disorders Mental disorder	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Nervous system disorders Cerebral infarction	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Nervous system disorders Altered state of consciousness	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Nervous system disorders Cerebellar infarction	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Nervous system disorders Cerebrovascular disorder	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Cardiac disorders Cardiac failure	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Cardiac disorders Angina unstable	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Cardiac disorders Coronary artery stenosis	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Cardiac disorders Ventricular fibrillation	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Vascular disorders Aortic dissection	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Emphysema	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Gastrointestinal disorders Colonic polyp	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastric ulcer	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
General disorders Thrombosis in device	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Compression fracture	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Spinal cord injury	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Brain contusion	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Meniscus lesion	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Skull fracture	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Upper limb fracture	0.20% 1/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.00% 0/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications In-stent coronary artery restenosis	0.00% 0/506 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.	0.19% 1/516 • At the start of the treatment, 3, 6, and 12 months after administration Analyzed: Safety analysis set - all participants who received at least 1 dose of open-label study drug.