BANTING: Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02739984
• Collaborator: (none)
• Enrollment: 424
• Locations: 66
• Arms: 2
• Actual Duration (Months): 14.6
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of 12 weeks of subcutaneous evolocumab taken monthly compared with subcutaneous placebo taken monthly on low density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes mellitus and high blood cholesterol on a maximally tolerated oral dose of statin of at least moderate-intensity.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia; Mixed Dyslipidemia; Type 2 Diabetes	Biological: Evolocumab; Drug: Placebo to Evolocumab	Phase 3

Detailed Description

This study will enroll adults with type 2 diabetes mellitus and elevated LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels on a stable, maximally tolerated statin dose of at least moderate-intensity at signing of the informed consent; statin therapy must remain unchanged during screening and the remainder of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 424 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab (AMG 145) on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia
• Actual Study Start Date: May 17, 2016
• Actual Primary Completion Date: Aug 3, 2017
• Actual Study Completion Date: Aug 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Drug: Placebo to Evolocumab; Administered by subcutaneous injection with an automated mini doser
Experimental: Evolocumab Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection with an automated mini doser; Other Names: Repatha AMG 145

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

2. Percent Change From Baseline in LDL-C at Week 12 [Baseline and week 12]

Secondary Outcome Measures

1. Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

2. Change From Baseline in LDL-C at Week 12 [Baseline and week 12]

3. Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

4. Percent Change From Baseline in Non-HDL-C at Week 12 [Baseline and week 12]

5. Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

6. Percent Change From Baseline in Apolipoprotein B at Week 12 [Baseline and week 12]

7. Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

8. Percent Change From Baseline in Total Cholesterol at Week 12 [Baseline and week 12]

9. Percentage of Participants With Mean LDL-C at Weeks 10 and 12 Less Than 70 mg/dL (1.8 mmol/L) [Weeks 10 and 12]

10. Percentage of Participants With LDL-C at Week 12 Less Than 70 mg/dL (1.8 mmol/L) [Week 12]

11. Percentage of Participants With at Least a 50% Reduction From Baseline in Mean LDL-C at Weeks 10 and 12 [Baseline and weeks 10 and 12]

12. Percentage of Participants With at Least a 50% Reduction From Baseline in LDL-C at Week 12 [Baseline and Week 12]

13. Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

14. Percent Change From Baseline in Lipoprotein(a) at Week 12 [Baseline and week 12]

15. Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

16. Percent Change From Baseline in Triglycerides at Week 12 [Baseline and week 12]

17. Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

18. Percent Change From Baseline in HDL-C at Week 12 [Baseline and week 12]

19. Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 [Baseline and weeks 10 and 12]

20. Percent Change From Baseline in VLDL-C at Week 12 [Baseline and week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥ 18 years

• Type 2 Diabetes Mellitus

• Hemoglobin A1c < 10%

• Stable diabetes therapy

• Must be on maximally tolerated dose of statin of at least moderate Intensity

• Fasting triglycerides ≤ 600 mg/dL

• Not at LDL-C or Non-HDL-C goal.

Exclusion Criteria:

• Moderate to severe renal dysfunction

• Uncontrolled hypertension

• Persistent active liver disease or hepatic dysfunction

• Has taken a cholesterylester transfer protein inhibitor in the last 12 months,

• Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tuscumbia	Alabama	United States	35674
2	Research Site	Phoenix	Arizona	United States	85012
3	Research Site	Lomita	California	United States	90717
4	Research Site	Los Angeles	California	United States	90057
5	Research Site	Roseville	California	United States	95661
6	Research Site	San Ramon	California	United States	94583
7	Research Site	Spring Valley	California	United States	91978
8	Research Site	Tarzana	California	United States	91356
9	Research Site	Walnut Creek	California	United States	94598
10	Research Site	Denver	Colorado	United States	80246
11	Research Site	Lakewood	Colorado	United States	80227
12	Research Site	Wilmington	Delaware	United States	19803
13	Research Site	Boca Raton	Florida	United States	33434
14	Research Site	Coral Gables	Florida	United States	33134
15	Research Site	Daytona Beach	Florida	United States	32117
16	Research Site	Fleming Island	Florida	United States	32003
17	Research Site	Hollywood	Florida	United States	33021
18	Research Site	Inverness	Florida	United States	34452
19	Research Site	Jacksonville	Florida	United States	32216
20	Research Site	Miami	Florida	United States	33135
21	Research Site	Miami	Florida	United States	33136
22	Research Site	West Palm Beach	Florida	United States	33401
23	Research Site	Dunwoody	Georgia	United States	30338
24	Research Site	Meridian	Idaho	United States	83642
25	Research Site	Chicago	Illinois	United States	60611
26	Research Site	Chicago	Illinois	United States	60612
27	Research Site	Chicago	Illinois	United States	60616
28	Research Site	Louisville	Kentucky	United States	40213
29	Research Site	Auburn	Maine	United States	04210
30	Research Site	Scarborough	Maine	United States	04074
31	Research Site	Salisbury	Maryland	United States	21804
32	Research Site	Methuen	Massachusetts	United States	01844
33	Research Site	Bay City	Michigan	United States	48706
34	Research Site	Tupelo	Mississippi	United States	38801
35	Research Site	Las Vegas	Nevada	United States	89148
36	Research Site	Albuquerque	New Mexico	United States	87106
37	Research Site	New Windsor	New York	United States	12553
38	Research Site	New York	New York	United States	10016
39	Research Site	New York	New York	United States	10029
40	Research Site	Shelby	North Carolina	United States	28150
41	Research Site	Tabor City	North Carolina	United States	28463
42	Research Site	Columbus	Ohio	United States	43203
43	Research Site	Norman	Oklahoma	United States	73069
44	Research Site	Austin	Texas	United States	78749
45	Research Site	Houston	Texas	United States	77070
46	Research Site	Suffolk	Virginia	United States	23435
47	Research Site	Edegem		Belgium	2650
48	Research Site	Leuven		Belgium	3000
49	Research Site	Liege		Belgium	4000
50	Research Site	Vancouver	British Columbia	Canada	V5Y 3W2
51	Research Site	Gatineau	Quebec	Canada	J8Y 6S8
52	Research Site	Montreal	Quebec	Canada	H1Y 3L1
53	Research Site	St-Jérôme	Quebec	Canada	J7Z 5T3
54	Research Site	Roma		Italy	00128
55	Research Site	Roma		Italy	00133
56	Research Site	Verona		Italy	37126
57	Research Site	Guadalajara	Jalisco	Mexico	44600
58	Research Site	Chihuahua		Mexico	31217
59	Research Site	Katowice		Poland	40-040
60	Research Site	Krakow		Poland	31-315
61	Research Site	Warszawa		Poland	02-018
62	Research Site	Wroclaw		Poland	50-306
63	Research Site	Almeria	Andalucía	Spain	04001
64	Research Site	Granada	Andalucía	Spain	18016
65	Research Site	Badalona	Cataluña	Spain	08916
66	Research Site	Barcelona	Cataluña	Spain	08036

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Jan 6, 2016
• Statistical Analysis Plan - Dec 22, 2016

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02739984
• Other Study ID Numbers: 20130287; 2015-004711-21
• First Posted: Apr 15, 2016
• Last Update Posted: Aug 31, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Amgen: diabetes; type 2 diabetes; high blood cholesterol; hypercholesterolemia; mixed dyslipidemia; high cholesterol; statin intolerant
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Hypercholesterolemia; Dyslipidemias; Evolocumab; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Of 853 patients screened, a total of 424 participants were randomized at 58 centers in Belgium, Canada, Italy, Mexico, Poland, Spain and the United States from 17 May 2016 to 05 May 2017.
Pre-assignment Detail	Participants received subcutaneous placebo during a 6-week screening period. Participants who completed the screening period and met final eligibility criteria were randomized in a 1:2 ratio to placebo or evolocumab. Randomization was stratified by low-density lipoprotein cholesterol (LDL-C) level (> or < 130 mg/dL).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Period Title: Overall Study
STARTED	143	281
Received Study Drug	141	280
COMPLETED	138	279
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Placebo	Evolocumab	Total
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.	Total of all reporting groups
Overall Participants	143	281	424
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (8.5)	62.5 (8.5)	62.5 (8.5)
Age, Customized (Count of Participants)
< 65 years	86 60.1%	159 56.6%	245 57.8%
65 - < 85 years	57 39.9%	122 43.4%	179 42.2%
≥ 85 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	65 45.5%	121 43.1%	186 43.9%
Male	78 54.5%	160 56.9%	238 56.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 16.8%	54 19.2%	78 18.4%
Not Hispanic or Latino	119 83.2%	227 80.8%	346 81.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	7 4.9%	8 2.8%	15 3.5%
Asian	2 1.4%	4 1.4%	6 1.4%
Black (or African American)	32 22.4%	41 14.6%	73 17.2%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.7%	2 0.5%
White	102 71.3%	223 79.4%	325 76.7%
Multiple	0 0%	1 0.4%	1 0.2%
Other	0 0%	2 0.7%	2 0.5%
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level (Count of Participants)
< 130 mg/dL	108 75.5%	213 75.8%	321 75.7%
≥ 130 mg/dL	35 24.5%	68 24.2%	103 24.3%
LDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	110.4 (33.0)	108.6 (31.0)	109.2 (31.6)
Non-High-density Lipoprotein Cholesterol (non-HDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	145.5 (33.9)	144.6 (34.9)	144.9 (34.5)
Apolipoprotein B Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	98.1 (22.1)	97.1 (23.3)	97.5 (22.9)
Total Cholesterol Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	190.7 (35.0)	188.2 (36.8)	189.1 (36.2)
Lipoprotein(a) Concentration (nmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nmol/L]	99.4 (122.8)	88.0 (111.5)	91.8 (115.4)
Triglycerides Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	177.3 (89.2)	184.2 (102.2)	181.9 (98.0)
High-density Lipoprotein Cholesterol (HDL-C) Concentraion (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	45.2 (12.2)	43.6 (12.9)	44.2 (12.7)
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	33.6 (14.3)	34.8 (15.4)	34.4 (15.0)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and Weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-0.84 (1.76)	-64.98 (1.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-64.14
	Confidence Interval	(2-Sided) 95%; -68.16 to -60.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.05
	Estimation Comments	Evolocumab - Placebo

2. Primary Outcome

Title	Percent Change From Baseline in LDL-C at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-1.14 (1.92)	-54.28 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-53.14
	Confidence Interval	(2-Sided) 95%; -57.56 to -48.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.25
	Estimation Comments	Evolocumab - Placebo

3. Secondary Outcome

Title	Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [mg/dL]	-8.3 (2.2)	-75.5 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-67.2
	Confidence Interval	(2-Sided) 95%; -72.1 to -62.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Evolocumab - Placebo

4. Secondary Outcome

Title	Change From Baseline in LDL-C at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [mg/dL]	-8.6 (2.3)	-64.4 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-55.8
	Confidence Interval	(2-Sided) 95%; -61.0 to -50.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.7
	Estimation Comments	Evolocumab - Placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-0.05 (1.63)	-56.62 (1.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-56.56
	Confidence Interval	(2-Sided) 95%; -60.28 to -52.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.89
	Estimation Comments	Evolocumab - Placebo

6. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-0.60 (1.79)	-46.89 (1.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-46.28
	Confidence Interval	(2-Sided) 95%; -50.42 to -42.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.10
	Estimation Comments	Evolocumab - Placebo

7. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	2.31 (1.58)	-50.17 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-52.48
	Confidence Interval	(2-Sided) 95%; -56.10 to -48.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.85
	Estimation Comments	Evolocumab - Placebo

8. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein B at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	1.78 (1.73)	-40.34 (1.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-42.12
	Confidence Interval	(2-Sided) 95%; -46.13 to -38.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.04
	Estimation Comments	Evolocumab - Placebo

9. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-1.13 (1.24)	-42.19 (0.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-41.06
	Confidence Interval	(2-Sided) 95%; -43.90 to -38.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.44
	Estimation Comments	Evolocumab - Placebo

10. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-1.23 (1.36)	-34.97 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-33.74
	Confidence Interval	(2-Sided) 95%; -36.87 to -30.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.59
	Estimation Comments	Evolocumab - Placebo

11. Secondary Outcome

Title	Percentage of Participants With Mean LDL-C at Weeks 10 and 12 Less Than 70 mg/dL (1.8 mmol/L)
Time Frame	Weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Number (95% Confidence Interval) [percentage of participants]	14.8 10.3%	92.7 33%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran Mantel Haenszel (CMH) test adjusted by the stratification factor (screening LDL-C level).
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	77.9
	Confidence Interval	(2-Sided) 95%; 70.0 to 83.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Evolocumab - Placebo

12. Secondary Outcome

Title	Percentage of Participants With LDL-C at Week 12 Less Than 70 mg/dL (1.8 mmol/L)
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Number (95% Confidence Interval) [percentage of participants]	15.4 10.8%	84.5 30.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran Mantel Haenszel (CMH) test adjusted by the stratification factor (screening LDL-C level).
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	69.1
	Confidence Interval	(2-Sided) 95%; 60.4 to 75.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Evolocumab - Placebo

13. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Reduction From Baseline in Mean LDL-C at Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Number (95% Confidence Interval) [percentage of participants]	0.7 0.5%	84.2 30%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran Mantel Haenszel (CMH) test adjusted by the stratification factor (screening LDL-C level).
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	83.5
	Confidence Interval	(2-Sided) 95%; 77.7 to 87.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Evolocumab - Placebo

14. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Reduction From Baseline in LDL-C at Week 12
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Number (95% Confidence Interval) [percentage of participants]	0.8 0.6%	65.5 23.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran Mantel Haenszel (CMH) test adjusted by the stratification factor (screening LDL-C level).
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	64.7
	Confidence Interval	(2-Sided) 95%; 57.7 to 70.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Evolocumab - Placebo

15. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	9.63 (3.29)	-30.87 (2.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-40.50
	Confidence Interval	(2-Sided) 95%; -48.11 to -32.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.87
	Estimation Comments	Evolocumab - Placebo

16. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	7.38 (3.06)	-25.18 (2.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-32.56
	Confidence Interval	(2-Sided) 95%; -39.58 to -25.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.57
	Estimation Comments	Evolocumab - Placebo

17. Secondary Outcome

Title	Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	6.61 (2.94)	-12.64 (2.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-19.25
	Confidence Interval	(2-Sided) 95%; -25.95 to -12.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.41
	Estimation Comments	Evolocumab - Placebo

18. Secondary Outcome

Title	Percent Change From Baseline in Triglycerides at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	4.81 (3.41)	-8.90 (2.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-13.70
	Confidence Interval	(2-Sided) 95%; -21.60 to -5.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.02
	Estimation Comments	Evolocumab - Placebo

19. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-2.57 (1.25)	7.23 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	9.80
	Confidence Interval	(2-Sided) 95%; 6.95 to 12.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.45
	Estimation Comments	Evolocumab - Placebo

20. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	-1.41 (1.38)	5.96 (1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	7.37
	Confidence Interval	(2-Sided) 95%; 4.19 to 10.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.62
	Estimation Comments	Evolocumab - Placebo

21. Secondary Outcome

Title	Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	3.42 (2.57)	-13.64 (1.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-17.06
	Confidence Interval	(2-Sided) 95%; -22.91 to -11.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.98
	Estimation Comments	Evolocumab - Placebo

22. Secondary Outcome

Title	Percent Change From Baseline in VLDL-C at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of the study drug (placebo or evolocumab).

Arm/Group Title	Placebo	Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
Measure Participants	141	280
Least Squares Mean (Standard Error) [percent change]	3.02 (2.94)	-10.31 (2.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Evolocumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, stratification factor (screening LDL-C level), scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-13.33
	Confidence Interval	(2-Sided) 95%; -20.09 to -6.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.44
	Estimation Comments	Evolocumab - Placebo

Adverse Events

Time Frame	From the first dose of study drug (placebo or evolocumab) to week 12.
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Placebo		Evolocumab
Arm/Group Description	Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.		Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.
All Cause Mortality
	Placebo		Evolocumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/141 (0%)		1/280 (0.4%)
Serious Adverse Events
	Placebo		Evolocumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/141 (1.4%)		14/280 (5%)
Cardiac disorders
Atrial fibrillation	0/141 (0%)		1/280 (0.4%)
Coronary artery disease	0/141 (0%)		2/280 (0.7%)
Gastrointestinal disorders
Peptic ulcer	1/141 (0.7%)		0/280 (0%)
General disorders
Sudden cardiac death	0/141 (0%)		1/280 (0.4%)
Infections and infestations
Cellulitis	0/141 (0%)		1/280 (0.4%)
Gastroenteritis viral	0/141 (0%)		1/280 (0.4%)
Osteomyelitis chronic	1/141 (0.7%)		0/280 (0%)
Pneumonia	0/141 (0%)		1/280 (0.4%)
Pneumonia bacterial	0/141 (0%)		1/280 (0.4%)
Sepsis	0/141 (0%)		1/280 (0.4%)
Injury, poisoning and procedural complications
Fracture displacement	0/141 (0%)		1/280 (0.4%)
Metabolism and nutrition disorders
Dehydration	0/141 (0%)		1/280 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/141 (0%)		1/280 (0.4%)
Nervous system disorders
Haemorrhagic stroke	0/141 (0%)		1/280 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/141 (0%)		4/280 (1.4%)
Sleep apnoea syndrome	0/141 (0%)		1/280 (0.4%)
Vascular disorders
Hypertension	0/141 (0%)		1/280 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Evolocumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/141 (13.5%)		37/280 (13.2%)
Gastrointestinal disorders
Diarrhoea	4/141 (2.8%)		6/280 (2.1%)
Infections and infestations
Pharyngitis	3/141 (2.1%)		0/280 (0%)
Urinary tract infection	2/141 (1.4%)		6/280 (2.1%)
Viral upper respiratory tract infection	4/141 (2.8%)		5/280 (1.8%)
Metabolism and nutrition disorders
Diabetes mellitus	5/141 (3.5%)		8/280 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	3/141 (2.1%)		2/280 (0.7%)
Nervous system disorders
Headache	3/141 (2.1%)		6/280 (2.1%)
Vascular disorders
Hypertension	0/141 (0%)		11/280 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.