Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1) (NCT NCT01926782)

NCT ID: NCT01926782

Last Updated: 2017-03-21

Results Overview

Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 803 participants
• Primary outcome timeframe: From Baseline to Week 24
• Results posted on: 2017-03-21

Participant Flow

The study was conducted at 97 sites in 8 countries. A total of 1491 subjects were screened between September 2013 and April 2014, 688 of whom were screen failures. Screen failures were mainly due to inclusion criteria not met.

Randomization was stratified according to statin therapy (with/ without) and cardiovascular risk (moderate vs. high/ very high) within the population receiving concomitant statin. Assignment to treatment arms was done using an Interactive Voice/Web Response System in 2:1:4 (Placebo: 75 mg: 300 mg) ratio after confirmation of selection criteria.

Participant milestones

Measure	Placebo Q2W With Concomitant Statin Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Placebo Q2W Without Concomitant Statin Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Overall Study STARTED	157	78	312	73	37	146
Overall Study Treated	157	78	312	72	37	146
Overall Study Completed 24 Weeks Treatment Period	137	68	285	58	31	120
Overall Study COMPLETED	129	65	272	53	29	105
Overall Study NOT COMPLETED	28	13	40	20	8	41

Reasons for withdrawal

Measure	Placebo Q2W With Concomitant Statin Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Placebo Q2W Without Concomitant Statin Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Overall Study Participant moved	2	0	1	1	0	3
Overall Study Physician Decision	0	2	1	1	0	0
Overall Study Other than specified	2	3	5	12	4	11
Overall Study Adverse Event	13	4	17	4	3	14
Overall Study Poor compliance to protocol	5	3	8	0	1	6
Overall Study Randomized and not treated	0	0	0	1	0	0
Overall Study Withdrawal by Subject	6	1	8	1	0	5
Overall Study Related to study drug administration	0	0	0	0	0	2

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1)

Baseline characteristics by cohort

Measure	Placebo Q2W With Concomitant Statin n=157 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) with stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin n=78 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin n=312 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W with stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Placebo Q2W Without Concomitant Statin n=73 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=146 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Total n=803 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 9.7 • n=93 Participants	60.7 years STANDARD_DEVIATION 9.1 • n=4 Participants	61.6 years STANDARD_DEVIATION 10 • n=27 Participants	59.4 years STANDARD_DEVIATION 10.2 • n=483 Participants	59.3 years STANDARD_DEVIATION 11.3 • n=36 Participants	59.2 years STANDARD_DEVIATION 10.8 • n=10 Participants	60.8 years STANDARD_DEVIATION 10.1 • n=115 Participants
Sex: Female, Male Female	56 Participants n=93 Participants	27 Participants n=4 Participants	122 Participants n=27 Participants	33 Participants n=483 Participants	23 Participants n=36 Participants	80 Participants n=10 Participants	341 Participants n=115 Participants
Sex: Female, Male Male	101 Participants n=93 Participants	51 Participants n=4 Participants	190 Participants n=27 Participants	40 Participants n=483 Participants	14 Participants n=36 Participants	66 Participants n=10 Participants	462 Participants n=115 Participants
Calculated LDL-C in mg/dL	112.1 mg/dL STANDARD_DEVIATION 37.3 • n=93 Participants	114.9 mg/dL STANDARD_DEVIATION 36 • n=4 Participants	112.4 mg/dL STANDARD_DEVIATION 32.8 • n=27 Participants	131 mg/dL STANDARD_DEVIATION 30.4 • n=483 Participants	148.4 mg/dL STANDARD_DEVIATION 36.8 • n=36 Participants	146.1 mg/dL STANDARD_DEVIATION 33.5 • n=10 Participants	122.1 mg/dL STANDARD_DEVIATION 36.9 • n=115 Participants
Calculated LDL-C in mmol/L	2.903 mmol/L STANDARD_DEVIATION 0.965 • n=93 Participants	2.977 mmol/L STANDARD_DEVIATION 0.933 • n=4 Participants	2.912 mmol/L STANDARD_DEVIATION 0.85 • n=27 Participants	3.392 mmol/L STANDARD_DEVIATION 0.787 • n=483 Participants	3.842 mmol/L STANDARD_DEVIATION 0.953 • n=36 Participants	3.785 mmol/L STANDARD_DEVIATION 0.868 • n=10 Participants	3.162 mmol/L STANDARD_DEVIATION 0.956 • n=115 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants without concomitant statin therapy): all randomized participants who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis At averaged Week 21 to 24	-1.6 percent change Standard Error 2.6	-54 percent change Standard Error 3.6	-56.9 percent change Standard Error 1.8
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis At Week 24	-0.3 percent change Standard Error 2.7	-50.2 percent change Standard Error 3.7	-52.7 percent change Standard Error 1.9

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants with concomitant statin therapy): all randomized participants who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model 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 this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis) At Week 24	-0.1 percent change Standard Error 2.3	-51.6 percent change Standard Error 3.3	-58.8 percent change Standard Error 1.6
Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis) At averaged Week 21 to 24	0.8 percent change Standard Error 2.0	-57.9 percent change Standard Error 2.8	-65.8 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Modified ITT (mITT) population (participants without concomitant statin therapy): all randomized and treated participants who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

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) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis	-0.4 percent change Standard Error 2.0	-54.6 percent change Standard Error 2.8	-59.4 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: mITT population

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) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=151 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=302 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis	-0.3 percent change Standard Error 2.1	-55.1 percent change Standard Error 3.0	-62.3 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants without concomitant statin therapy)

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	0.3 percent change Standard Error 2.1	-51.8 percent change Standard Error 2.9	-58.4 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants with concomitant statin therapy)

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	1.1 percent change Standard Error 2.2	-45.3 percent change Standard Error 3.1	-55.3 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: mITT population (participants without concomitant statin therapy)

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis	-0.5 percent change Standard Error 2.0	-53.9 percent change Standard Error 2.7	-60.0 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: mITT population (participants with concomitant statin therapy)

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=151 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=302 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis	1.4 percent change Standard Error 1.9	-47.3 percent change Standard Error 2.8	-58.0 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo B ITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=34 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=138 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-0.7 percent change Standard Error 2.3	-39.0 percent change Standard Error 3.3	-40.2 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo B ITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=146 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=292 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	3.1 percent change Standard Error 1.8	-36.7 percent change Standard Error 2.6	-45.1 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo B mITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis	-0.3 percent change Standard Error 2.0	-42.0 percent change Standard Error 2.7	-44.8 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo B mITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=142 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=74 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=286 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis	3.1 percent change Standard Error 1.7	-38.3 percent change Standard Error 2.5	-47.2 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Non-HDL-C ITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-0.3 percent change Standard Error 2.5	-43.6 percent change Standard Error 3.4	-43.3 percent change Standard Error 1.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Non-HDL-C ITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	0.3 percent change Standard Error 1.9	-41.6 percent change Standard Error 2.7	-49.7 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Non-HDL-C mITT population (participants without concomitant statin therapy)

Adjusted LS means and standard errors at Week 24 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). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis	0.1 percent change Standard Error 2.1	-47.2 percent change Standard Error 2.8	-48.9 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Non-HDL-C mITT population (participants with concomitant statin therapy)

Adjusted LS means and standard errors at Week 24 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). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=151 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=302 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis	0.2 percent change Standard Error 1.8	-44.4 percent change Standard Error 2.5	-52.6 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Total-C ITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-1.9 percent change Standard Error 1.9	-32.5 percent change Standard Error 2.6	-33.3 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Total-C ITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	-0.8 percent change Standard Error 1.4	-30.0 percent change Standard Error 2.0	-35.8 percent change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo B ITT population (participants without concomitant statin therapy)

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. Apo B ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=34 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=138 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-2.3 percent change Standard Error 1.7	-40.8 percent change Standard Error 2.5	-46.4 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo B ITT population (participants with concomitant statin therapy).

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. Apo B ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=146 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=292 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	3.6 percent change Standard Error 1.8	-33.0 percent change Standard Error 2.5	-41.2 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Non-HDL-C ITT population (participants without concomitant statin therapy).

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. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-0.4 percent change Standard Error 1.8	-45.8 percent change Standard Error 2.5	-49.9 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Non-HDL-C ITT population (participants with concomitant statin therapy).

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. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	0.6 percent change Standard Error 1.9	-37.4 percent change Standard Error 2.7	-46.5 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Total-C ITT population (participants without concomitant statin therapy)

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. Total-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis	-1.0 percent change Standard Error 1.4	-33.4 percent change Standard Error 2.0	-37.4 percent change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Total-C ITT population (participants with concomitant statin therapy)

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. Total-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis	-0.1 percent change Standard Error 1.3	-26.5 percent change Standard Error 1.9	-32.9 percent change Standard Error 1.0

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population (participants without concomitant statin therapy)

Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 &<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from 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 included in imputation model. ITT population (subjects with or without concomitant statin therapy).

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL (Without Concomitant Statin Therapy) at Week 24 - ITT Analysis	9.4 percentage of participants	84.9 percentage of participants	78.9 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population (participants with concomitant statin therapy)

Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 &<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from 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 included in imputation model. ITT population (subjects with or without concomitant statin therapy).

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (With Concomitant Statin Therapy) at Week 24 - ITT Analysis	22.2 percentage of participants	82.5 percentage of participants	85.2 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population (participants without concomitant statin therapy)

Adjusted percentages at Week 24 were from 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). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
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) (Without Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis	11.3 percentage of participants	93.0 percentage of participants	88.6 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population (participants with concomitant statin therapy)

Adjusted percentages at Week 24 were from 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). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=151 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=302 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
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) (With Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis	22.5 percentage of participants	86.4 percentage of participants	89.5 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population (participants without concomitant statin therapy)

Adjusted percentages at Week 24 were obtained from 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 population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	3.3 percentage of participants	57.7 percentage of participants	62.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population (participants with concomitant statin therapy)

Adjusted percentages at Week 24 were obtained from 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 population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	10.9 percentage of participants	74.4 percentage of participants	80.4 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population (participants without concomitant statin therapy)

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=70 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=141 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	2.1 percentage of participants	61.7 percentage of participants	70.4 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population (participants with concomitant statin therapy)

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=151 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=302 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	10.8 percentage of participants	77.4 percentage of participants	84.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants without concomitant statin therapy)

Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression 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 population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	6.4 percent change Standard Error 3.4	-14.0 percent change Standard Error 4.8	-21.3 percent change Standard Error 2.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants with concomitant statin therapy)

Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression 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 population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	9.8 percent change Standard Error 2.4	-16.9 percent change Standard Error 3.3	-19.3 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants without concomitant statin therapy)

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	-5.5 percent change Standard Error 3.3	-26.9 percent change Standard Error 4.7	-28.9 percent change Standard Error 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants with concomitant statin therapy)

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	7.0 percent change Standard Error 2.3	-12.4 percent change Standard Error 3.2	-19.6 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: HDL-C ITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	-5.3 percent change Standard Error 1.7	-0.1 percent change Standard Error 2.4	2.5 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: HDL-C ITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	-1.5 percent change Standard Error 1.2	6.0 percent change Standard Error 1.7	3.6 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: HDL-C ITT population (participants without concomitant statin therapy)

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. HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	-0.9 percent change Standard Error 1.6	2.5 percent change Standard Error 2.2	6.0 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: HDL-C ITT population (participants with concomitant statin therapy)

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. HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	0.4 percent change Standard Error 1.2	7.6 percent change Standard Error 1.8	5.7 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants without concomitant statin therapy)

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	-1.5 percent change Standard Error 3.4	-9.8 percent change Standard Error 4.9	-13.4 percent change Standard Error 2.5

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population (participants with concomitant statin therapy)

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	-0.1 percent change Standard Error 2.4	-6.7 percent change Standard Error 3.3	-15.2 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants without concomitant statin therapy)

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=37 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=144 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	1.8 percent change Standard Error 3.2	-18.3 percent change Standard Error 4.6	-12.3 percent change Standard Error 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: ITT population (participants with concomitant statin therapy)

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=156 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=76 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=308 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	0.5 percent change Standard Error 2.4	-7.3 percent change Standard Error 3.5	-13.1 percent change Standard Error 1.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo A1 ITT population (participants without concomitant statin therapy)

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. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=34 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=138 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	-1.4 percent change Standard Error 1.3	3.1 percent change Standard Error 1.9	5.2 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo A1 ITT population (participants with concomitant statin therapy)

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. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=146 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=292 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis	2.9 percent change Standard Error 1.0	6.5 percent change Standard Error 1.4	5.5 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo A1 ITT population (participants without concomitant statin therapy)

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. Apo A1 ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=71 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=34 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=138 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	-1.8 percent change Standard Error 1.3	2.4 percent change Standard Error 1.8	4.6 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: Apo A1 ITT population (participants with concomitant statin therapy)

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. Apo A1 ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

Outcome measures

Measure	Placebo Q2W Without Concomitant Statin n=146 Participants Two Subcutaneous (SC) injections of placebo (for alirocumab) every two weeks (Q2W) without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin n=75 Participants One SC injection of each Alirocumab 75 mg and placebo Q2W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin n=292 Participants Two SC injections of Alirocumab 150 mg every 4 weeks (Q4W) alternating with two SC injections of placebo Q4W without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg every two weeks (Q2W) from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis	2.7 percent change Standard Error 1.0	6.1 percent change Standard Error 1.4	6.0 percent change Standard Error 0.7

Adverse Events

Placebo Q2W

Serious events: 33 serious events

Other events: 118 other events

Deaths: 0 deaths

Alirocumab 75 mg Q2W/Up 150 mg Q2W

Serious events: 13 serious events

Other events: 55 other events

Deaths: 0 deaths

Alirocumab 300 mg Q4W/Up 150 mg Q2W

Serious events: 53 serious events

Other events: 229 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Q2W n=229 participants at risk Two SC injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W n=115 participants at risk One SC injection of Alirocumab 150 mg Q4W alternating with 2 SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W n=458 participants at risk Two SC injections of Alirocumab 300 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Cardiac disorders Acute myocardial infarction	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Angina pectoris	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Angina unstable	0.87% 2/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Atrial fibrillation	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Atrial flutter	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Cardiac failure chronic	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Cardiac failure congestive	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Cardiogenic shock	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Coronary artery disease	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Coronary artery stenosis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Mitral valve incompetence	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Myocardial infarction	1.3% 3/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Myocardial ischaemia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Palpitations	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Sinus bradycardia	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Cardiac disorders Ventricular tachycardia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Eye disorders Visual acuity reduced	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Diverticular perforation	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Duodenal ulcer perforation	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Epiploic appendagitis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Incarcerated inguinal hernia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Incarcerated umbilical hernia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Oesophageal spasm	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Small intestinal obstruction	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Volvulus	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Chest pain	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Coronary artery restenosis	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Impaired healing	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Non-Cardiac chest pain	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 4/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Oedema peripheral	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Pelvic mass	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Immune system disorders Drug hypersensitivity	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Immune system disorders Hypersensitivity	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Acute hepatitis c	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Appendicitis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Diverticulitis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Gastroenteritis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Pneumonia	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	1.7% 2/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Meniscus injury	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Tendon injury	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Traumatic fracture	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Metabolism and nutrition disorders Dehydration	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Foot deformity	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Monarthritis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenocortical carcinoma	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibrous histiocytoma	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papillary-mucinous carcinoma of pancreas	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Nervous system disorders Cerebrovascular accident	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Nervous system disorders Cervical radiculopathy	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Nervous system disorders Dizziness	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Nervous system disorders Transient ischaemic attack	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.44% 2/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Psychiatric disorders Completed suicide	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Renal and urinary disorders Calculus ureteric	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Renal and urinary disorders Nephrolithiasis	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Renal and urinary disorders Renal failure	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Renal and urinary disorders Renal failure acute	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Renal and urinary disorders Ureteric obstruction	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Reproductive system and breast disorders Benign prostatic hyperplasia	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Reproductive system and breast disorders Prostatic obstruction	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Asthma	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.3% 3/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.66% 3/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.22% 1/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Aortic aneurysm	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Deep vein thrombosis	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Hypertensive crisis	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Hypotension	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Peripheral ischaemia	0.44% 1/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Vascular compression	0.00% 0/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.87% 1/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	0.00% 0/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Other adverse events

Measure	Placebo Q2W n=229 participants at risk Two SC injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.	Alirocumab 75 mg Q2W/Up 150 mg Q2W n=115 participants at risk One SC injection of Alirocumab 150 mg Q4W alternating with 2 SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.	Alirocumab 300 mg Q4W/Up 150 mg Q2W n=458 participants at risk Two SC injections of Alirocumab 300 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk subjects) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk subjects) at Week 8.
Gastrointestinal disorders Diarrhoea	7.4% 17/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	3.5% 4/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	5.5% 25/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Gastrointestinal disorders Nausea	6.6% 15/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 7/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	4.1% 19/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Injection site reaction	7.0% 16/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	8.7% 10/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	16.2% 74/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
General disorders Non-Cardiac chest pain	2.2% 5/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	5.2% 6/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	1.5% 7/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Bronchitis	5.2% 12/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 7/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	4.1% 19/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Nasopharyngitis	7.9% 18/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	8.7% 10/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	8.5% 39/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Sinusitis	4.8% 11/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	3.5% 4/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 28/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Upper respiratory tract infection	7.9% 18/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	7.0% 8/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	9.0% 41/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Infections and infestations Urinary tract infection	4.4% 10/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 7/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 28/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Arthralgia	6.6% 15/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.1% 7/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.3% 29/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Back pain	6.1% 14/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	2.6% 3/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.3% 29/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Musculoskeletal and connective tissue disorders Muscle spasms	5.7% 13/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	3.5% 4/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	2.2% 10/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Nervous system disorders Headache	5.7% 13/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	5.2% 6/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	6.3% 29/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Vascular disorders Hypertension	5.2% 12/229 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	3.5% 4/115 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	3.5% 16/458 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 56 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
• Publication restrictions are in place

Restriction type: OTHER