Trial Outcomes & Findings for Caduet vs Usual Care in Subjects With Hypertension and Additional Risk Factors (NCT NCT00407537)

Last Updated: 2021-01-28

Results Overview

Framingham prediction of 10-year risk of CHD: Gender-specific prediction equations formulated to predict CHD risk according to age, diabetes, smoking, blood pressure categories, and total cholesterol and low density lipoprotein (LDL) cholesterol categories. The coefficients were used to derive the score calculated at the end of study treatment (Month 12).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1531 participants

Primary outcome timeframe

Baseline, Month 12

Results posted on

2021-01-28

Participant Flow

This was a cluster randomized study: the unit of randomization was the investigator, ie, participants were screened before the investigator was randomized. A total of 136 sites were cluster randomized.

Prior to group assignment of investigators (who were the unit of randomization), participants were consented and screened for enrollment eligibility; participant selection for enrollment took place before investigator assignment. A total of 1,531 participants were enrolled and attended baseline visit; 1,461 participants received treatment.

Participant milestones

Participant milestones
Measure	Caduet Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Overall Study STARTED	779	682
Overall Study Eligible for Efficacy Analysis	760	657
Overall Study COMPLETED	686	638
Overall Study NOT COMPLETED	93	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Caduet Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Overall Study Death	5	2
Overall Study Adverse Event	36	0
Overall Study Lost to Follow-up	12	19
Overall Study Other	6	7
Overall Study Withdrawal by Subject	34	16

Baseline Characteristics

Caduet vs Usual Care in Subjects With Hypertension and Additional Risk Factors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Caduet as Assigned n=783 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care as Assigned n=678 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.	Total n=1461 Participants Total of all reporting groups
Age, Customized < 18 years	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Age, Customized 18 to 44 years	58 participants n=99 Participants	55 participants n=107 Participants	113 participants n=206 Participants
Age, Customized 45 to 64 years	450 participants n=99 Participants	361 participants n=107 Participants	811 participants n=206 Participants
Age, Customized > = 65 years	275 participants n=99 Participants	262 participants n=107 Participants	537 participants n=206 Participants
Sex: Female, Male Female	368 Participants n=99 Participants	334 Participants n=107 Participants	702 Participants n=206 Participants
Sex: Female, Male Male	415 Participants n=99 Participants	344 Participants n=107 Participants	759 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Month 12

Population: Full Analysis Set (FAS) included all subjects, in either treatment group, who had blood pressure and lipid data from at least 1 follow-up visit. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=748 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=655 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Framingham 10-year Risk of Total Coronary Heart Disease (CHD) at Month 12	12.5 percent risk Standard Deviation 8.26	16.3 percent risk Standard Deviation 10.51

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=745 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=637 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Framingham 10-year Risk of Total CHD at Month 4	12.5 percent risk Standard Deviation 7.96	16.3 percent risk Standard Deviation 10.80

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

European SCORE: designed to measure cardiovascular disease mortality; computed using age, gender, whether a person lives in a low risk or high risk region, measured total cholesterol, measured HDL cholesterol, systolic blood pressure, and current smoking status. The coefficients were used to derive the score calculated after 12 months of study treatment (Month 12).

Outcome measures

Outcome measures
Measure	Caduet n=748 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=655 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
European Systematic COronary Risk Evaluation (SCORE) 10-year Risk of Fatal Cardiovascular Disease (CVD) at Month 12	3.0 percent risk Standard Deviation 2.89	3.7 percent risk Standard Deviation 3.69

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=745 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=637 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
European SCORE 10-year Risk of Fatal CVD at Month 4	3.1 percent risk Standard Deviation 3.13	3.7 percent risk Standard Deviation 3.69

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Stroke risk calculated from the Framingham risk for CVD (CHD, stroke, intermittent claudication, congestive heart failure) multiplied by a gender-specific "calibration factor" for the stroke component risk. Coefficients were used to derive the score calculated at the end of study treatment (Month 12).

Outcome measures

Outcome measures
Measure	Caduet n=748 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=655 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Framingham 10-year Risk of Stroke at Month 12	3.7 percent risk Standard Deviation 2.25	4.9 percent risk Standard Deviation 2.87

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=745 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=637 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Framingham 10-year Risk of Stroke at Month 4	3.7 percent risk Standard Deviation 2.21	4.9 percent risk Standard Deviation 2.81

SECONDARY outcome

Timeframe: Baseline, Month 4, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Framingham prediction of 10-year risk of CHD: Gender-specific prediction equations formulated to predict CHD risk according to age, diabetes, smoking, blood pressure categories, and total cholesterol and low density lipoprotein (LDL) cholesterol categories. Change from baseline calculated as mean at observation minus mean at Baseline.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in Framingham 10-year Risk of Developing Total CHD Month 4	-7.2705 percent risk Interval -7.9 to -6.64	-2.5155 percent risk Interval -3.19 to -1.84
Change From Baseline in Framingham 10-year Risk of Developing Total CHD Month 12	-7.2374 percent risk Interval -7.87 to -6.61	-2.5167 percent risk Interval -3.19 to -1.84

SECONDARY outcome

Timeframe: Baseline, Month 4, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

European SCORE: designed to measure cardiovascular disease mortality; computed using age, gender, whether a person lives in a low risk or high risk region, measured total cholesterol, measured HDL cholesterol, systolic blood pressure, and current smoking status. Change from baseline calculated as mean at observation minus mean at Baseline.

Outcome measures

Outcome measures
Measure	Caduet n=748 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=655 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline European SCORE 10-year Risk of Developing Fatal CVD Month 4	-1.8438 percent risk Interval -2.06 to -1.63	-0.9678 percent risk Interval -1.2 to -0.74
Change From Baseline European SCORE 10-year Risk of Developing Fatal CVD Month 12	-1.9693 percent risk Interval -2.16 to -1.77	-0.9963 percent risk Interval -1.21 to -0.79

SECONDARY outcome

Timeframe: Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Outcome measures

Outcome measures
Measure	Caduet n=759 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Mean Systolic and Diastolic Blood Pressure at Month 4 Systolic	133.5 mmHg Standard Deviation 14.32	134.5 mmHg Standard Deviation 14.96
Mean Systolic and Diastolic Blood Pressure at Month 4 Diastolic	80.7 mmHg Standard Deviation 8.74	81.1 mmHg Standard Deviation 9.32

SECONDARY outcome

Timeframe: Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Mean Systolic and Diastolic Blood Pressure at Month 12 Systolic	130.6 mmHg Standard Deviation 13.84	134.3 mmHg Standard Deviation 15.21
Mean Systolic and Diastolic Blood Pressure at Month 12 Diastolic	79.2 mmHg Standard Deviation 8.39	81.1 mmHg Standard Deviation 9.27

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=759 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in Systolic Blood Pressure (SBP) at Month 4	-15.3088 mmHG Interval -17.02 to -13.6	-12.1619 mmHG Interval -14.0 to -10.32

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=759 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in Diastolic Blood Pressure (DBP) at Month 4	-8.3024 mmHG Interval -9.24 to -7.36	-6.6908 mmHG Interval -7.7 to -5.68

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS, number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in SBP at Month 12	-18.2409 mmHg Interval -19.94 to -16.55	-12.4903 mmHg Interval -14.32 to -10.66

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing to data.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in DBP at Month 12	-10.0128 mmHg Interval -10.96 to -9.07	-6.8429 mmHg Interval -7.86 to -5.83

SECONDARY outcome

Timeframe: Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), and Triglyceride blood concentrations.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Mean Lipid Parameters at Month 4 TC	156.0 mg/dL Standard Deviation 34.14	195.2 mg/dL Standard Deviation 37.03
Mean Lipid Parameters at Month 4 LDL	80.9 mg/dL Standard Deviation 28.47	116.4 mg/dL Standard Deviation 32.47
Mean Lipid Parameters at Month 4 HDL	47.6 mg/dL Standard Deviation 13.93	46.8 mg/dL Standard Deviation 13.49
Mean Lipid Parameters at Month 4 Triglycerides	143.5 mg/dL Standard Deviation 83.26	164.8 mg/dL Standard Deviation 95.74

SECONDARY outcome

Timeframe: Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), and Triglyceride blood concentrations.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Mean Lipid Parameters at Month 12 TC	163.3 mg/dL Standard Deviation 38.42	196.6 mg/dL Standard Deviation 36.36
Mean Lipid Parameters at Month 12 LDL	87.1 mg/dL Standard Deviation 32.40	117.3 mg/dL Standard Deviation 31.57
Mean Lipid Parameters at Month 12 HDL	47.3 mg/dL Standard Deviation 13.48	47.1 mg/dL Standard Deviation 13.61
Mean Lipid Parameters at Month 12 Triglycerides	151.5 mg/dL Standard Deviation 98.61	166.4 mg/dL Standard Deviation 98.53

SECONDARY outcome

Timeframe: Baseline, Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), and Triglyceride blood concentrations. Change from baseline measured as mean at Month 4 minus mean at Baseline.

Outcome measures

Outcome measures
Measure	Caduet n=752 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=630 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in Lipid Parameters at Month 4 TC	-42.7542 mg/dL Interval -46.35 to -39.15	-3.8144 mg/dL Interval -7.75 to 0.12
Change From Baseline in Lipid Parameters at Month 4 LDL	-38.2765 mg/dL Interval -41.52 to -35.03	-2.9628 mg/dL Interval -6.5 to 0.58
Change From Baseline in Lipid Parameters at Month 4 HDL	-0.2060 mg/dL Interval -1.07 to 0.65	-1.1978 mg/dL Interval -2.13 to -0.26
Change From Baseline in Lipid Parameters at Month 4 Triglycerides	-20.5645 mg/dL Interval -27.3 to -13.83	3.0828 mg/dL Interval -4.26 to 10.43

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), and Triglyceride blood concentrations.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Change From Baseline in Lipid Parameters at Month 12 TC	-37.1024 mg/dL Interval -40.52 to -33.69	-4.0368 mg/dL Interval -7.71 to -0.36
Change From Baseline in Lipid Parameters at Month 12 LDL	-33.2420 mg/dL Interval -36.17 to -30.32	-3.4168 mg/dL Interval -6.58 to -0.25
Change From Baseline in Lipid Parameters at Month 12 HDL	-0.4339 mg/dL Interval -1.41 to 0.54	-1.0105 mg/dL Interval -2.06 to 0.04
Change From Baseline in Lipid Parameters at Month 12 Triglycerides	-15.2270 mg/dL Interval -23.12 to -7.33	3.0398 mg/dL Interval -5.51 to 11.59

SECONDARY outcome

Timeframe: Month 4, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Goals set at \<140/90 mmHg according to the seventh Joint National Committee (JNC) on prevention, detection, evaluation, and treatment of high blood pressure and \<140/90 mm Hg or \<130/80 mm Hg for diabetics ccording to the European Society of Cardiology (ESC) guidelines.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for Blood Pressure at 4 and 12 Months JNC Month 4	65.2 percentage of participants	62.6 percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for Blood Pressure at 4 and 12 Months JNC Month 12	76.1 percentage of participants	60.6 percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for Blood Pressure at 4 and 12 Months ESC Month 4	48.6 percentage of participants	46.0 percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for Blood Pressure at 4 and 12 Months ESC Month 12	58.2 percentage of participants	47.5 percentage of participants

SECONDARY outcome

Timeframe: Month 4, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Goal set at \<100 mg/dL according to the United States (US) National Cholesterol Education Program Adult Treatment Panel 3 and at \<80 mg/dL according to the European (EU) Society of Cardiology guidelines.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for LDL at 4 and 12 Months US Month 4	77.3 Percentage of participants	28.2 Percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for LDL at 4 and 12 Months US Month 12	71.9 Percentage of participants	28.8 Percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for LDL at 4 and 12 Months EU Month 4	52.4 Percentage of participants	13.3 Percentage of participants
Percentage of Participants at Conventional Treatment Goals According to Global and Local Guidelines for LDL at 4 and 12 Months EU Month 12	46.7 Percentage of participants	11.5 Percentage of participants

SECONDARY outcome

Timeframe: Month 4, Month 12

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Treatments indicative of prescribed medications other than study provided Caduet.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 4: anti-hypertensive and/or lipid lowering	648 participants	642 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 4: anti-hypertensive	647 participants	637 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 4: lipid lowering	45 participants	202 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 4: anti-hypertensive and lipid lowering	44 participants	197 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 12: anti-hypertensive and/or lipid lowering	655 participants	642 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 12: anti-hypertensive	654 participants	638 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 12: lipid lowering	46 participants	208 participants
Number of Participants With Lipid and Antihypertensive Treatments Used at 4 and 12 Months Month 12: anti-hypertensive and lipid lowering	45 participants	204 participants

SECONDARY outcome

Timeframe: Month 4

Population: FAS. Number of participants analyzed refers to number of participants contributing data.

Treatments indicative of prescribed medications other than study provided Caduet.

Outcome measures

Outcome measures
Measure	Caduet n=760 Participants Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=657 Participants Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Number of Participants With Increase of Treatment Dosages After 4 Months. Increased dose	30 Participants	90 Participants
Number of Participants With Increase of Treatment Dosages After 4 Months. increased dose of anti-hypertensive medications	30 Participants	88 Participants
Number of Participants With Increase of Treatment Dosages After 4 Months. increased dose of lipid lowering medications	0 Participants	2 Participants
Number of Participants With Increase of Treatment Dosages After 4 Months. increase in either medication	4 Participants	45 Participants
Number of Participants With Increase of Treatment Dosages After 4 Months. increase in both medications	0 Participants	0 Participants

Adverse Events

Caduet

Serious events: 51 serious events

Other events: 356 other events

Deaths: 0 deaths

Usual Care

Serious events: 22 serious events

Other events: 289 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Caduet n=779 participants at risk Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=682 participants at risk Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Blood and lymphatic system disorders Anaemia	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute coronary syndrome	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute myocardial infarction	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.29% 2/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina unstable	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Coronary artery disease	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.29% 2/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Macular hole	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Normal tension glaucoma	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous haemorrhage	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dysphagia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Sudden cardiac death	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Biliary colic	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholestasis	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Jaundice	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Acute sinusitis	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Appendicitis	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Arthritis infective	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infection	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.39% 3/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fractured coccyx	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Hand fracture	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Caduet n=779 participants at risk Open label amlodipine besylate/atorvastatin calcium (Caduet) single pill combination at multiple doses: 5/10, 10/10, 5/20, 10/20 mg prescribed at the investigator's discretion.	Usual Care n=682 participants at risk Full choice of any locally approved (and not contra indicated) anti-hypertensive and/or lipid lowering drugs, including, but not limited to amlodipine and atorvastatin, according to local clinical practice.
Infections and infestations Tracheobronchitis	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	2.1% 16/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 14/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urethritis	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.88% 6/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urogenital infection fungal	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Vaginal infection	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral infection	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.44% 3/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Excoriation	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Eye injury	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Foreign body trauma	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Injury	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Joint injury	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina unstable	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradyarrhythmia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Coronary artery disease	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Left ventricular hypertrophy	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	1.2% 9/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 5/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Supraventricular tachyarrhythmia	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Supraventricular tachycardia	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	0.26% 2/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Ventricular extrasystoles	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Congenital, familial and genetic disorders Corneal dystrophy	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Deafness unilateral	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Hearing impaired	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Hypoacusis	0.00% 0/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.15% 1/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Inner ear disorder	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Otosclerosis	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	0.13% 1/779 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/682 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.