Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01709513
• Collaborator: Sanofi (Industry)
• Enrollment: 314
• Locations: 70
• Arms: 3
• Actual Duration (Months): 56
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia	Drug: Atorvastatin; Drug: Ezetimibe; Drug: Alirocumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 314 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins
• Actual Study Start Date: Sep 30, 2012
• Actual Primary Completion Date: May 31, 2014
• Actual Study Completion Date: May 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Atorvastatin (statin rechallenge arm) Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).	Drug: Atorvastatin; Atorvastatin over-encapsulated tablets.; Drug: Placebo; Placebo for alirocumab, ezitimibe and atorvastatin.
Active Comparator: Ezetimibe Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Drug: Ezetimibe; Ezetimibe over-encapsulated tablet.; Other Names: Zetia ; Drug: Placebo; Placebo for alirocumab, ezitimibe and atorvastatin.
Experimental: Alirocumab 75 mg/ up to 150 mg Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Drug: Alirocumab; Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.; Other Names: REGN727/SAR236553 ; Drug: Placebo; Placebo for alirocumab, ezitimibe and atorvastatin.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis [From Baseline to Week 24]

   Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Secondary Outcome Measures

1. Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis [From Baseline to Week 24]

   Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

2. Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis [From Baseline to Week 12]

   Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

3. Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis [From Baseline to Week 12]

   Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).

4. Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis [From Baseline to Week 24]

   Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

5. Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis [From Baseline to Week 24]

   Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).

6. Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis [From Baseline to Week 24]

   Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

7. Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis [From Baseline to Week 24]

   Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).

8. Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis [From Baseline to Week 24]

   Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

9. Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis [From Baseline to Week 12]

   Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

10. Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis [From Baseline to Week 12]

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

11. Percent Change From Baseline in Total-C at Week 12 - ITT Analysis [From Baseline to Week 12]

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

12. Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis [Up to Week 24]

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).

13. Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis [Up to Week 24]

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).

14. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [Up to Week 24]

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).

15. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis [Up to Week 24]

    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).

16. Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis [From Baseline to Week 24]

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

17. Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis [From Baseline to Week 24]

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

18. Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis [From Baseline to Week 24]

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

19. Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis [From Baseline to Week 24]

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

20. Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis [From Baseline to Week 12]

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

21. Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis [From Baseline to Week 12]

    Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis

22. Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis [From Baseline to Week 12]

    Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.

23. Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis [From Baseline to Week 12]

    Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.

Other Outcome Measures

1. Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE) [From Baseline up to Week 24]

   Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.

2. Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis [From Baseline up to Week 24]

Eligibility Criteria

Criteria

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

Inclusion:

1. Patients with primary hypercholesterolemia [Heterozygous Familial Hypercholesterolemia (heFH) or non-FH] with moderate, high or very high CV risk and a history of statin intolerance

2. Provide signed informed consent

Exclusion:

1. Calculated serum LDL-C <70 mg/dL (1.81 mmol/L) and very high CV risk at the screening visit

2. Calculated serum LDL-C <100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the screening visit

3. A 10-year fatal cardiovascular disease risk score <1% at the screening visit

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anaheim	California	United States
2		Beverly Hills	California	United States
3		Mission Viejo	California	United States
4		Newport Beach	California	United States
5		Northridge	California	United States
6		Thousand Oaks	California	United States
7		Hartford	Connecticut	United States
8		Boynton Beach	Florida	United States
9		Jacksonville	Florida	United States
10		Lakeland	Florida	United States
11		Pembroke Pines	Florida	United States
12		Sarasota	Florida	United States
13		Tampa	Florida	United States
14		Trinity	Florida	United States
15		Addison	Illinois	United States
16		Chicago	Illinois	United States
17		Indianapolis	Indiana	United States
18		Kansas City	Kansas	United States
19		Auburn	Maine	United States
20		Boston	Massachusetts	United States
21		Minneapolis	Minnesota	United States
22		Rochester	Minnesota	United States
23		Saint Louis	Missouri	United States
24		Clifton	New Jersey	United States
25		New York	New York	United States
26		Poughkeepsie	New York	United States
27		Durham	North Carolina	United States
28		Cincinnati	Ohio	United States
29		Marion	Ohio	United States
30		Danville	Pennsylvania	United States
31		Philadelphia	Pennsylvania	United States
32		Port Matilda	Pennsylvania	United States
33		Scranton	Pennsylvania	United States
34		Wilkes-Barre	Pennsylvania	United States
35		Summerville	South Carolina	United States
36		Kingsport	Tennessee	United States
37		Nashville	Tennessee	United States
38		Dallas	Texas	United States
39		Fort Worth	Texas	United States
40		Salt Lake City	Utah	United States
41		Richmond	Virginia	United States
42		Feldkirch		Austria
43		Graz		Austria
44		Innsbruck		Austria
45		Chicoutimi	Quebec	Canada
46		Montreal (2 locations)	Quebec	Canada
47		Sainte-Foy	Quebec	Canada
48		Bron		France
49		Dijon		France
50		Lille		France
51		Paris		France
52		Saint-Herblain		France
53		Venissieux		France
54		Holon		Israel
55		Jerusalem		Israel
56		Ofakim		Israel
57		Safed		Israel
58		Tel-Hashomer		Israel
59		Cinisello Balsamo		Italy
60		Napoli		Italy
61		Palermo		Italy
62		Roma		Italy
63		Oslo (2 Locations)		Norway
64		Burton-on-Trent		United Kingdom
65		Chesterfield		United Kingdom
66		Isle Of White		United Kingdom
67		Londonderry/N. Ireland		United Kingdom
68		Peterborough		United Kingdom
69		Salford		United Kingdom
70		Stevenage		United Kingdom

Sponsors and Collaborators

• Regeneron Pharmaceuticals
• Sanofi

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

• Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 2014 Sep 19.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01709513
• Other Study ID Numbers: R727-CL-1119
• First Posted: Oct 18, 2012
• Last Update Posted: Jun 23, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Hypercholesterolemia; Atorvastatin; Ezetimibe

Study Results

Participant Flow

Recruitment Details	The study was conducted at 67 sites in 8 countries. Overall, 519 participants were screened between 28 September 2012 and 11 August 2013, 158 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. After screening, 361 participants entered into a 4-week single blind placebo run-in period.
Pre-assignment Detail	At the end of the single blind placebo run-in period, eligible participants were randomized to treatment arms centrally using a 2:2:1 (alirocumab:ezetimibe:atorvastatin) ratio. Randomization was stratified according to prior history of myocardial infarction or ischemic stroke. 314 participants were randomized.

Arm/Group Title	Atorvastatin (Statin Rechallenge Arm)	Ezetimibe (Active Comparator)	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable LMT.	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Period Title: Overall Study
STARTED	63	125	126
Treated	63	124	126
COMPLETED	42	82	96
NOT COMPLETED	21	43	30

Baseline Characteristics

Arm/Group Title	Atorvastatin (Statin Rechallenge Arm)	Ezetimibe (Active Comparator)	Alirocumab 75 mg/ up to 150 mg	Total
Arm/Group Description	Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable lipid-modifying therapy (LMT).	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.	Total of all reporting groups
Overall Participants	63	125	126	314
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (9.5)	62.8 (10.1)	64.1 (9.0)	63.4 (9.5)
Sex: Female, Male (Count of Participants)
Female	28 44.4%	58 46.4%	56 44.4%	142 45.2%
Male	35 55.6%	67 53.6%	70 55.6%	172 54.8%
Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	187.3 (59.5)	193.5 (70.9)	191.1 (72.7)	191.3 (69.3)
LDL-C in mmol/L (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	4.85 (1.54)	5.011 (1.837)	4.951 (1.883)	4.954 (1.796)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis
Description	Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-14.6 (2.2)	-45.0 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-30.4
	Confidence Interval	(2-Sided) 95%; -36.6 to -24.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis
Description	Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	118	123
Least Squares Mean (Standard Error) [percent change]	-17.1 (2.0)	-52.2 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 5% level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-35.1
	Confidence Interval	(2-Sided) 95%; -40.7 to -29.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis
Description	Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-15.6 (2.0)	-47.0 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-31.5
	Confidence Interval	(2-Sided) 95%; -36.9 to -26.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis
Description	Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	118	123
Least Squares Mean (Standard Error) [percent change]	-18.0 (1.8)	-51.2 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-33.1
	Confidence Interval	(2-Sided) 95%; -38.0 to -28.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	116	122
Least Squares Mean (Standard Error) [percent change]	-11.2 (1.7)	-36.3 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.1
	Confidence Interval	(2-Sided) 95%; -29.8 to -20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis
Description	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	95	109
Least Squares Mean (Standard Error) [percent change]	-14.4 (1.4)	-42.6 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-28.2
	Confidence Interval	(2-Sided) 95%; -32.1 to -24.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-14.6 (1.7)	-40.2 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.6
	Confidence Interval	(2-Sided) 95%; -30.4 to -20.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis
Description	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	118	123
Least Squares Mean (Standard Error) [percent change]	-17.1 (1.5)	-46.9 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-29.8
	Confidence Interval	(2-Sided) 95%; -33.9 to -25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-10.9 (1.4)	-31.8 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-20.8
	Confidence Interval	(2-Sided) 95%; -24.7 to -17.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Apo B ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	116	122
Least Squares Mean (Standard Error) [percent change]	-11.6 (1.5)	-36.1 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-24.5
	Confidence Interval	(2-Sided) 95%; -28.7 to -20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Non-HDL-C ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-15.8 (1.5)	-41.5 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.7
	Confidence Interval	(2-Sided) 95%; -29.9 to -21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Total-C ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75/ up to 150
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	-11.6 (1.2)	-32.7 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-21.1
	Confidence Interval	(2-Sided) 95%; -24.5 to -17.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
Description	Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Number [percentage of participants]	4.4 7%	41.9 33.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95%; 6.9 to 55.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	118	123
Number [percentage of participants]	5.6 8.9%	51.2 41%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	24.9
	Confidence Interval	(2-Sided) 95%; 8.6 to 71.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Description	Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Number [percentage of participants]	0.8 1.3%	32.5 26%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a last observation carried forward (LOCF) approach followed by Exact conditional logistic regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Exact Conditional Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	71.5
	Confidence Interval	(2-Sided) 95%; 11.1 to 3022.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	118	123
Number [percentage of participants]	0.8 1.3%	39.0 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a LOCF approach followed by Exact conditional logistic regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Exact Conditional Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	109.8
	Confidence Interval	(2-Sided) 95%; 16.5 to 4759.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Description	Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Mean (Standard Error) [percent change]	-7.3 (2.5)	-25.9 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance ≤ 0.05.
	Method	Regression, Robust
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-18.7
	Confidence Interval	(2-Sided) 95%; -25.5 to -11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	6.8 (1.7)	7.7 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetimibe, Alirocumab 75 mg/ up to 150 mg
	Comments	Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.6997
	Comments	Threshold for significance ≤ 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -3.8 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Description	Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Mean (Standard Error) [percent change]	-3.6 (2.8)	-9.3 (2.7)

20. Secondary Outcome

Title	Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Description	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	116	122
Least Squares Mean (Standard Error) [percent change]	2.9 (1.2)	4.8 (1.2)

21. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis
Description	Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Lipoprotein(a) ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Mean (Standard Error) [percent change]	-4.5 (2.3)	-21.7 (2.2)

22. Secondary Outcome

Title	Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis
Description	Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

HDL-C ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Least Squares Mean (Standard Error) [percent change]	7.6 (1.2)	9.0 (1.2)

23. Secondary Outcome

Title	Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis
Description	Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Fasting Triglycerides ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	122	126
Mean (Standard Error) [percent change]	-9.4 (2.6)	-8.0 (2.5)

24. Secondary Outcome

Title	Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis
Description	Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Apo A-1 ITT population.

Arm/Group Title	Ezetimibe	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	116	122
Least Squares Mean (Standard Error) [percent change]	3.9 (1.0)	5.5 (1.0)

25. Other Pre-specified Outcome

Title	Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)
Description	Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
Time Frame	From Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Atorvastatin (Statin Rechallenge Arm)	Ezetimibe (Active Comparator)	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	63	124	126
Any skeletal muscle-related AE	46.0 73%	41.1 32.9%	32.5 25.8%
Leading to treatment discontinuation	22.2 35.2%	20.2 16.2%	15.9 12.6%

26. Other Pre-specified Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis
Time Frame	From Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atorvastatin (Statin Rechallenge Arm)	Ezetimibe (Active Comparator)	Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.	Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Measure Participants	54	106	112
Mean (Standard Deviation) [percent change]	-31.9 (25.1)	-15.2 (22.4)	-47.3 (22.7)

Adverse Events

Time Frame	From Baseline up to the Last Double-Blind Injection Date + 70 Days
Adverse Event Reporting Description	Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
Arm/Group Title	Atorvastatin		Ezetimibe		Alirocumab 75 mg/ up to 150 mg
Arm/Group Description	Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 22 weeks added to stable LMT.		Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo for alirocumab SC injection Q2W for 22 weeks added to stable LMT.		Alirocumab 75 mg SC injection Q2W for 22 weeks and placebo for atorvastatin/ezetimibe over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL--C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
All Cause Mortality
	Atorvastatin		Ezetimibe		Alirocumab 75 mg/ up to 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorvastatin		Ezetimibe		Alirocumab 75 mg/ up to 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/63 (11.1%)		10/124 (8.1%)		12/126 (9.5%)
Cardiac disorders
Acute myocardial infarction	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Angina unstable	1/63 (1.6%)		0/124 (0%)		1/126 (0.8%)
Aortic valve incompetence	0/63 (0%)		1/124 (0.8%)		0/126 (0%)
Atrial fibrillation	0/63 (0%)		1/124 (0.8%)		1/126 (0.8%)
Cardiovascular disorder	0/63 (0%)		1/124 (0.8%)		0/126 (0%)
Coronary artery disease	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Gastrointestinal disorders
Nausea	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Peritoneal haemorrhage	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Small intestinal obstruction	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Vomiting	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
General disorders
Non-Cardiac chest pain	1/63 (1.6%)		4/124 (3.2%)		0/126 (0%)
Immune system disorders
Hypersensitivity	0/63 (0%)		1/124 (0.8%)		0/126 (0%)
Infections and infestations
Appendicitis	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Pyelonephritis	0/63 (0%)		1/124 (0.8%)		0/126 (0%)
Wound infection	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Injury, poisoning and procedural complications
Hip fracture	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Post procedural haematoma	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Traumatic arthritis	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Haemarthrosis	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Osteoarthritis	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Clear cell renal cell carcinoma	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Colon cancer	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Malignant melanoma	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Ovarian epithelial cancer	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Nervous system disorders
Loss of consciousness	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Transient ischaemic attack	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Psychiatric disorders
Depression	0/63 (0%)		0/124 (0%)		1/126 (0.8%)
Vascular disorders
Aortic aneurysm	1/63 (1.6%)		0/124 (0%)		0/126 (0%)
Hypertensive crisis	0/63 (0%)		1/124 (0.8%)		0/126 (0%)
Other (Not Including Serious) Adverse Events
	Atorvastatin		Ezetimibe		Alirocumab 75 mg/ up to 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/63 (55.6%)		63/124 (50.8%)		57/126 (45.2%)
General disorders
Fatigue	5/63 (7.9%)		4/124 (3.2%)		6/126 (4.8%)
Infections and infestations
Nasopharyngitis	2/63 (3.2%)		10/124 (8.1%)		8/126 (6.3%)
Upper respiratory tract infection	2/63 (3.2%)		5/124 (4%)		7/126 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/63 (7.9%)		9/124 (7.3%)		6/126 (4.8%)
Back pain	5/63 (7.9%)		7/124 (5.6%)		5/126 (4%)
Muscle spasms	7/63 (11.1%)		9/124 (7.3%)		5/126 (4%)
Muscular weakness	4/63 (6.3%)	4	2/124 (1.6%)	2	1/126 (0.8%)	1
Myalgia	17/63 (27%)		29/124 (23.4%)		31/126 (24.6%)
Nervous system disorders
Headache	4/63 (6.3%)		6/124 (4.8%)		6/126 (4.8%)
Paraesthesia	4/63 (6.3%)		0/124 (0%)		4/126 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

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

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