Trial Outcomes & Findings for Long Term Safety Study of PRALUENT (NCT NCT03694197)

NCT ID: NCT03694197

Last Updated: 2021-06-15

Results Overview

An AE is any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. AEs include serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of special interest (AESI). AESI include local injection site reactions, general allergic events, elevated alanine aminotransferase (ALT) levels greater than or equal to (≥) 3 upper limit normal (ULN) (if baseline is less than (\<) ULN)/ALT ≥2 x ULN (if baseline ≥ ULN), neurologic events, neurocognitive events (according to Customized Medical Dictionary for Regulatory Activities \[MedDRA\] Query \[CMQ\] by Sponsor grouping and CMQ by FDA grouping), cataract, new onset diabetes (NOD), hepatic disorders, and diabetes mellitus (DM)/diabetic complications.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 1389 participants
• Primary outcome timeframe: After first administration of study drug through the last dose of study drug plus 2 weeks, up to 80 weeks
• Results posted on: 2021-06-15

Participant Flow

The 1389 participants who completed double-blind treatment and the end-of-study (EOS) visit in R727-CL-1532 (NCT02957682) signed consent and were screened for this open-label study (EOS visit corresponded to day 1/visit 1 of this study).

First subcutaneous (SC) injection was administered in the clinic (day 1/visit 1). Four of the1389 participants discontinued on day 1 before treatment: 2 discontinued due to failure to meet inclusion/exclusion criteria,1 withdrew consent, and 1 discontinued due to adverse event (AE). A total of 1385 participants received any study drug on day 1.

Participant milestones

Measure	Alirocumab 75 Q2W/Up150 Q2W All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Overall Study STARTED	1385
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1385

Reasons for withdrawal

Measure	Alirocumab 75 Q2W/Up150 Q2W All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Overall Study Adverse Event	9
Overall Study Protocol became inconvenient to participate	1
Overall Study Physician Decision	4
Overall Study Study terminated by sponsor	1350
Overall Study Participant moved	5
Overall Study Participant withdrew consent	10
Overall Study Related to IMP administration	1
Overall Study Not disclosed	5

Baseline Characteristics

Long Term Safety Study of PRALUENT

Baseline characteristics by cohort

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Age, Continuous	64.6 Years STANDARD_DEVIATION 8.63 • n=5 Participants
Sex: Female, Male Female	527 Participants n=5 Participants
Sex: Female, Male Male	858 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1372 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race/Ethnicity, Customized White	1178 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	81 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	118 Participants n=5 Participants

PRIMARY outcome

Timeframe: After first administration of study drug through the last dose of study drug plus 2 weeks, up to 80 weeks

Population: Safety analysis set (SAF): All participants who received any study drug

An AE is any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. AEs include serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of special interest (AESI). AESI include local injection site reactions, general allergic events, elevated alanine aminotransferase (ALT) levels greater than or equal to (≥) 3 upper limit normal (ULN) (if baseline is less than (<) ULN)/ALT ≥2 x ULN (if baseline ≥ ULN), neurologic events, neurocognitive events (according to Customized Medical Dictionary for Regulatory Activities [MedDRA] Query [CMQ] by Sponsor grouping and CMQ by FDA grouping), cataract, new onset diabetes (NOD), hepatic disorders, and diabetes mellitus (DM)/diabetic complications.

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any treatment emergent adverse event (TEAE)	568 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any treatment emergent serious adverse event (SAE)	89 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any TEAE leading to death	5 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any TEAE leading to permanent treatment discontinuation	9 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any neurocognitive disorders TEAE (by Sponsor CMQ)	4 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any neurocognitive disorders TEAE (by FDA CMQ)	0 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any NOD; # analyzed = # of participants w/out diabetes at baseline	15 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any hepatic disorders TEAE	14 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any neurological TEAE	15 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any general allergic TEAE	25 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks At least one treatment-emergent injection site reaction	22 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any cataract TEAE	5 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any elevated ALT ≥3 ULN	1 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any DM/diabetic complications TEAE; # analyzed = # of participants w/diabetes at baseline	41 Participants
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks Any DM/diabetic complications TEAE; # analyzed = # of participants w/out diabetes at baseline	3 Participants

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Baseline	117.8 Milligrams per decilitre (mg/dL) Standard Deviation 40.67
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Week 8	58.9 Milligrams per decilitre (mg/dL) Standard Deviation 37.31
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Week 12	63.6 Milligrams per decilitre (mg/dL) Standard Deviation 40.79
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Week 24	56.2 Milligrams per decilitre (mg/dL) Standard Deviation 36.59
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Week 72	52.2 Milligrams per decilitre (mg/dL) Standard Deviation 38.80
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time Week 48	56.8 Milligrams per decilitre (mg/dL) Standard Deviation 36.13

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change in LDL-C From Baseline Over Time Week 12	-44.64 Percent Change Standard Deviation 35.338
Percent Change in LDL-C From Baseline Over Time Week 48	-52.35 Percent Change Standard Deviation 27.929
Percent Change in LDL-C From Baseline Over Time Week 72	-51.21 Percent Change Standard Deviation 32.742
Percent Change in LDL-C From Baseline Over Time Week 8	-48.74 Percent Change Standard Deviation 31.121
Percent Change in LDL-C From Baseline Over Time Week 24	-50.75 Percent Change Standard Deviation 30.249

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Total Cholesterol (Total-C) Values From Baseline Over Time Baseline	199.5 mg/dL Standard Deviation 48.88
Total Cholesterol (Total-C) Values From Baseline Over Time Week 8	139.5 mg/dL Standard Deviation 44.76
Total Cholesterol (Total-C) Values From Baseline Over Time Week 12	145.0 mg/dL Standard Deviation 48.68
Total Cholesterol (Total-C) Values From Baseline Over Time Week 24	137.3 mg/dL Standard Deviation 44.18
Total Cholesterol (Total-C) Values From Baseline Over Time Week 48	139.5 mg/dL Standard Deviation 44.53
Total Cholesterol (Total-C) Values From Baseline Over Time Week 72	131.7 mg/dL Standard Deviation 43.25

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Total-C Over Time Week 8	-28.68 Percent Change Standard Deviation 20.158
Percent Change From Baseline in Total-C Over Time Week 12	-25.99 Percent Change Standard Deviation 23.058
Percent Change From Baseline in Total-C Over Time Week 24	-29.98 Percent Change Standard Deviation 20.930
Percent Change From Baseline in Total-C Over Time Week 72	-31.55 Percent Change Standard Deviation 22.238
Percent Change From Baseline in Total-C Over Time Week 48	-30.89 Percent Change Standard Deviation 21.004

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Lipoprotein a (Lp(a)) Values From Baseline Over Time Baseline	39.7 mg/dL Standard Deviation 47.86
Lipoprotein a (Lp(a)) Values From Baseline Over Time Week 8	35.0 mg/dL Standard Deviation 41.99
Lipoprotein a (Lp(a)) Values From Baseline Over Time Week 12	32.7 mg/dL Standard Deviation 39.42
Lipoprotein a (Lp(a)) Values From Baseline Over Time Week 48	38.6 mg/dL Standard Deviation 50.66
Lipoprotein a (Lp(a)) Values From Baseline Over Time Week 72	40.4 mg/dL Standard Deviation 56.47
Lipoprotein a (Lp(a)) Values From Baseline Over Time Week 24	33.9 mg/dL Standard Deviation 42.54

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Lp(a) Over Time Week 12	10.63 Percent Change Standard Deviation 228.659
Percent Change From Baseline in Lp(a) Over Time Week 24	-6.80 Percent Change Standard Deviation 110.827
Percent Change From Baseline in Lp(a) Over Time Week 48	-7.89 Percent Change Standard Deviation 116.831
Percent Change From Baseline in Lp(a) Over Time Week 72	-22.23 Percent Change Standard Deviation 28.233
Percent Change From Baseline in Lp(a) Over Time Week 8	-12.69 Percent Change Standard Deviation 35.452

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Baseline	152.4 mg/dL Standard Deviation 48.81
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Week 8	88.5 mg/dL Standard Deviation 43.54
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Week 12	94.3 mg/dL Standard Deviation 48.77
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Week 24	87.3 mg/dL Standard Deviation 43.56
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Week 48	88.9 mg/dL Standard Deviation 44.25
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time Week 72	80.9 mg/dL Standard Deviation 42.67

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Non-HDL-C Over Time Week 12	-36.89 Percent Change Standard Deviation 29.567
Percent Change From Baseline in Non-HDL-C Over Time Week 24	-41.47 Percent Change Standard Deviation 26.763
Percent Change From Baseline in Non-HDL-C Over Time Week 72	-43.28 Percent Change Standard Deviation 29.534
Percent Change From Baseline in Non-HDL-C Over Time Week 8	-40.35 Percent Change Standard Deviation 27.470
Percent Change From Baseline in Non-HDL-C Over Time Week 48	-42.33 Percent Change Standard Deviation 28.728

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Baseline	47.1 mg/dL Standard Deviation 13.92
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Week 8	51.0 mg/dL Standard Deviation 14.82
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Week 12	50.6 mg/dL Standard Deviation 13.95
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Week 24	49.9 mg/dL Standard Deviation 14.80
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Week 48	50.5 mg/dL Standard Deviation 14.66
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time Week 72	50.8 mg/dL Standard Deviation 14.61

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in HDL-C Over Time Week 8	10.54 Percent Change Standard Deviation 22.735
Percent Change From Baseline in HDL-C Over Time Week 12	10.33 Percent Change Standard Deviation 21.933
Percent Change From Baseline in HDL-C Over Time Week 24	8.53 Percent Change Standard Deviation 21.824
Percent Change From Baseline in HDL-C Over Time Week 48	9.81 Percent Change Standard Deviation 23.690
Percent Change From Baseline in HDL-C Over Time Week 72	9.24 Percent Change Standard Deviation 21.505

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Fasting Triglycerides (TGs) Values From Baseline Over Time Baseline	179.2 mg/dL Standard Deviation 146.51
Fasting Triglycerides (TGs) Values From Baseline Over Time Week 8	154.8 mg/dL Standard Deviation 113.05
Fasting Triglycerides (TGs) Values From Baseline Over Time Week 12	162.2 mg/dL Standard Deviation 182.00
Fasting Triglycerides (TGs) Values From Baseline Over Time Week 24	169.3 mg/dL Standard Deviation 161.45
Fasting Triglycerides (TGs) Values From Baseline Over Time Week 48	171.1 mg/dL Standard Deviation 131.35
Fasting Triglycerides (TGs) Values From Baseline Over Time Week 72	156.9 mg/dL Standard Deviation 65.21

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Fasting TGs Over Time Week 8	-4.68 Percent Change Standard Deviation 49.230
Percent Change From Baseline in Fasting TGs Over Time Week 12	-4.29 Percent Change Standard Deviation 40.748
Percent Change From Baseline in Fasting TGs Over Time Week 24	0.42 Percent Change Standard Deviation 54.118
Percent Change From Baseline in Fasting TGs Over Time Week 48	1.54 Percent Change Standard Deviation 69.156
Percent Change From Baseline in Fasting TGs Over Time Week 72	-5.97 Percent Change Standard Deviation 41.440

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Apolipoprotein B (Apo B) Values From Baseline Over Time Baseline	103.8 mg/dL Standard Deviation 27.25
Apolipoprotein B (Apo B) Values From Baseline Over Time Week 8	62.5 mg/dL Standard Deviation 27.63
Apolipoprotein B (Apo B) Values From Baseline Over Time Week 12	68.0 mg/dL Standard Deviation 31.32
Apolipoprotein B (Apo B) Values From Baseline Over Time Week 24	61.5 mg/dL Standard Deviation 26.20
Apolipoprotein B (Apo B) Values From Baseline Over Time Week 48	63.7 mg/dL Standard Deviation 26.40
Apolipoprotein B (Apo B) Values From Baseline Over Time Week 72	58.5 mg/dL Standard Deviation 25.82

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Apo B Over Time Week 8	-36.51 Percent Change Standard Deviation 34.460
Percent Change From Baseline in Apo B Over Time Week 12	-34.48 Percent Change Standard Deviation 27.905
Percent Change From Baseline in Apo B Over Time Week 24	-38.16 Percent Change Standard Deviation 24.867
Percent Change From Baseline in Apo B Over Time Week 72	-39.04 Percent Change Standard Deviation 26.383
Percent Change From Baseline in Apo B Over Time Week 48	-37.93 Percent Change Standard Deviation 23.767

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Baseline	145.3 mg/dL Standard Deviation 24.95
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Week 8	148.5 mg/dL Standard Deviation 24.73
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Week 12	149.4 mg/dL Standard Deviation 25.38
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Week 24	150.7 mg/dL Standard Deviation 26.36
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Week 48	152.6 mg/dL Standard Deviation 25.96
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time Week 72	151.4 mg/dL Standard Deviation 26.03

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Percent Change From Baseline in Apo A1 Over Time Week 8	5.07 Percent Change Standard Deviation 13.385
Percent Change From Baseline in Apo A1 Over Time Week 12	2.99 Percent Change Standard Deviation 13.638
Percent Change From Baseline in Apo A1 Over Time Week 24	5.35 Percent Change Standard Deviation 14.108
Percent Change From Baseline in Apo A1 Over Time Week 48	4.77 Percent Change Standard Deviation 13.836
Percent Change From Baseline in Apo A1 Over Time Week 72	1.21 Percent Change Standard Deviation 13.170

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Female participants who received any study drug); Here, "Number Analyzed" = Number of female participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=527 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Week 72	58.600 International units per litre (IU/L) Standard Deviation 24.5205
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Baseline	30.155 International units per litre (IU/L) Standard Deviation 13.1090
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Week 8	33.794 International units per litre (IU/L) Standard Deviation 14.4459
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Week 12	30.779 International units per litre (IU/L) Standard Deviation 13.0946
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Week 24	31.260 International units per litre (IU/L) Standard Deviation 13.7344
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Week 48	29.585 International units per litre (IU/L) Standard Deviation 13.9792
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time LH Week 72	29.248 International units per litre (IU/L) Standard Deviation 11.0829
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Baseline	57.948 International units per litre (IU/L) Standard Deviation 26.7383
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Week 8	59.264 International units per litre (IU/L) Standard Deviation 24.7912
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Week 12	54.279 International units per litre (IU/L) Standard Deviation 23.9923
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Week 24	57.664 International units per litre (IU/L) Standard Deviation 25.9830
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time FSH Week 48	56.529 International units per litre (IU/L) Standard Deviation 25.1408

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Female participants who received any study drug); Here, "Number Analyzed" = Number of female participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=527 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time FSH Week 8	-0.765 IU/L Standard Deviation 12.0083
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time FSH Week 12	-0.984 IU/L Standard Deviation 12.1584
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time FSH Week 24	-0.575 IU/L Standard Deviation 8.7780
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time FSH Week 48	-0.877 IU/L Standard Deviation 15.9972
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time FSH Week 72	-1.861 IU/L Standard Deviation 8.6119
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time LH Week 8	2.730 IU/L Standard Deviation 8.2258
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time LH Week 12	1.882 IU/L Standard Deviation 8.2884
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time LH Week 24	0.939 IU/L Standard Deviation 6.3694
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time LH Week 48	0.367 IU/L Standard Deviation 8.5631
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time LH Week 72	0.222 IU/L Standard Deviation 6.8910

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Male participants who received any study drug); Here, "Number Analyzed" = Number of male participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=858 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Baseline	8.006 International units per litre (IU/L) Standard Deviation 7.4451
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Week 8	7.959 International units per litre (IU/L) Standard Deviation 7.5500
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Week 12	7.766 International units per litre (IU/L) Standard Deviation 6.8204
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Week 24	8.268 International units per litre (IU/L) Standard Deviation 8.1355
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Week 48	9.597 International units per litre (IU/L) Standard Deviation 11.2138
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time FSH Week 72	10.005 International units per litre (IU/L) Standard Deviation 13.2973
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Baseline	6.500 International units per litre (IU/L) Standard Deviation 4.2832
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Week 8	7.094 International units per litre (IU/L) Standard Deviation 4.7226
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Week 12	6.688 International units per litre (IU/L) Standard Deviation 4.4079
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Week 24	6.931 International units per litre (IU/L) Standard Deviation 4.8597
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Week 48	7.677 International units per litre (IU/L) Standard Deviation 6.5478
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time LH Week 72	8.173 International units per litre (IU/L) Standard Deviation 8.9083

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Male participants who received any study drug); Here, "Number Analyzed" = Number of male participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=858 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time FSH Week 72	2.458 IU/L Standard Deviation 13.4730
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time LH Week 8	0.535 IU/L Standard Deviation 2.4847
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time LH Week 12	-0.136 IU/L Standard Deviation 3.2638
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time LH Week 24	0.582 IU/L Standard Deviation 4.4964
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time LH Week 48	1.015 IU/L Standard Deviation 6.6344
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time LH Week 72	1.964 IU/L Standard Deviation 9.3028
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time FSH Week 8	0.285 IU/L Standard Deviation 3.7264
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time FSH Week 12	-0.598 IU/L Standard Deviation 4.1076
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time FSH Week 24	0.331 IU/L Standard Deviation 6.0522
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time FSH Week 48	0.960 IU/L Standard Deviation 10.3803

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Female participants who received any study drug); Here, "Number Analyzed" = Number of female participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=527 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Baseline	55.589 picomoles per litre (pmol/L) Standard Deviation 80.8238
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Week 8	58.676 picomoles per litre (pmol/L) Standard Deviation 69.0119
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Week 12	59.673 picomoles per litre (pmol/L) Standard Deviation 74.7587
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Week 24	64.304 picomoles per litre (pmol/L) Standard Deviation 103.8955
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Week 48	64.503 picomoles per litre (pmol/L) Standard Deviation 102.1595
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time Week 72	57.926 picomoles per litre (pmol/L) Standard Deviation 67.1795

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Female participants who received any study drug); Here, "Number Analyzed" = Number of female participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=527 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time Week 8	4.272 pmol/L Standard Deviation 77.1561
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time Week 12	9.262 pmol/L Standard Deviation 73.1050
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time Week 24	7.869 pmol/L Standard Deviation 78.4151
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time Week 48	11.763 pmol/L Standard Deviation 97.5350
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time Week 72	9.569 pmol/L Standard Deviation 38.0952

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Male participants who received any study drug); Here, "Number Analyzed" = Number of male participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=858 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Baseline	13.4370 nanomoles per litre (nmol/L) Standard Deviation 6.36321
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Week 8	14.5802 nanomoles per litre (nmol/L) Standard Deviation 5.99821
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Week 12	14.2443 nanomoles per litre (nmol/L) Standard Deviation 6.77070
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Week 24	13.5818 nanomoles per litre (nmol/L) Standard Deviation 6.11269
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Week 48	13.4798 nanomoles per litre (nmol/L) Standard Deviation 7.04977
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time Week 72	12.7538 nanomoles per litre (nmol/L) Standard Deviation 6.37408

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (Male participants who received any study drug); Here, "Number Analyzed" = Number of male participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=858 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time Week 8	0.6030 nmol/L Standard Deviation 4.46401
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time Week 12	0.7965 nmol/L Standard Deviation 4.74765
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time Week 48	0.0498 nmol/L Standard Deviation 6.34201
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time Week 72	1.2569 nmol/L Standard Deviation 5.29335
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time Week 24	0.1946 nmol/L Standard Deviation 5.89220

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Alanine Aminotransferase Values From Baseline Over Time Baseline	0.516 U/L (Units per Liter) Standard Deviation 0.3218
Alanine Aminotransferase Values From Baseline Over Time Week 8	0.468 U/L (Units per Liter) Standard Deviation 0.2745
Alanine Aminotransferase Values From Baseline Over Time Week 12	0.505 U/L (Units per Liter) Standard Deviation 0.4940
Alanine Aminotransferase Values From Baseline Over Time Week 24	0.493 U/L (Units per Liter) Standard Deviation 0.2851
Alanine Aminotransferase Values From Baseline Over Time Week 48	0.533 U/L (Units per Liter) Standard Deviation 0.3267
Alanine Aminotransferase Values From Baseline Over Time Week 72	0.468 U/L (Units per Liter) Standard Deviation 0.2340

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Alanine Aminotransferase Over Time Week 8	-0.025 U/L Standard Deviation 0.3006
Change From Baseline in Alanine Aminotransferase Over Time Week 12	0.009 U/L Standard Deviation 0.5189
Change From Baseline in Alanine Aminotransferase Over Time Week 24	-0.036 U/L Standard Deviation 0.3294
Change From Baseline in Alanine Aminotransferase Over Time Week 48	-0.027 U/L Standard Deviation 0.3052
Change From Baseline in Alanine Aminotransferase Over Time Week 72	-0.062 U/L Standard Deviation 0.1872

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Aspartate Aminotransferase Values From Baseline Over Time Baseline	0.553 U/L Standard Deviation 0.2516
Aspartate Aminotransferase Values From Baseline Over Time Week 8	0.520 U/L Standard Deviation 0.2536
Aspartate Aminotransferase Values From Baseline Over Time Week 12	0.527 U/L Standard Deviation 0.2698
Aspartate Aminotransferase Values From Baseline Over Time Week 24	0.544 U/L Standard Deviation 0.3071
Aspartate Aminotransferase Values From Baseline Over Time Week 48	0.565 U/L Standard Deviation 0.2773
Aspartate Aminotransferase Values From Baseline Over Time Week 72	0.556 U/L Standard Deviation 0.2256

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Aspartate Aminotransferase Over Time Week 8	-0.022 U/L Standard Deviation 0.2856
Change From Baseline in Aspartate Aminotransferase Over Time Week 12	-0.017 U/L Standard Deviation 0.3004
Change From Baseline in Aspartate Aminotransferase Over Time Week 24	-0.013 U/L Standard Deviation 0.2901
Change From Baseline in Aspartate Aminotransferase Over Time Week 48	-0.019 U/L Standard Deviation 0.2390
Change From Baseline in Aspartate Aminotransferase Over Time Week 72	-0.037 U/L Standard Deviation 0.1730

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Alkaline Phosphatase Values From Baseline Over Time Baseline	0.601 U/L Standard Deviation 0.1865
Alkaline Phosphatase Values From Baseline Over Time Week 8	0.635 U/L Standard Deviation 0.2151
Alkaline Phosphatase Values From Baseline Over Time Week 12	0.605 U/L Standard Deviation 0.1865
Alkaline Phosphatase Values From Baseline Over Time Week 24	0.602 U/L Standard Deviation 0.2012
Alkaline Phosphatase Values From Baseline Over Time Week 48	0.602 U/L Standard Deviation 0.2657
Alkaline Phosphatase Values From Baseline Over Time Week 72	0.553 U/L Standard Deviation 0.1678

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Alkaline Phosphatase Over Time Week 8	0.009 U/L Standard Deviation 0.1371
Change From Baseline in Alkaline Phosphatase Over Time Week 12	0.013 U/L Standard Deviation 0.1203
Change From Baseline in Alkaline Phosphatase Over Time Week 48	0.024 U/L Standard Deviation 0.2333
Change From Baseline in Alkaline Phosphatase Over Time Week 72	-0.011 U/L Standard Deviation 0.1029
Change From Baseline in Alkaline Phosphatase Over Time Week 24	0.006 U/L Standard Deviation 0.1152

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Total Bilirubin Values From Baseline Over Time Baseline	10.76 micromoles per litre (umol/L) Standard Deviation 4.736
Total Bilirubin Values From Baseline Over Time Week 8	10.01 micromoles per litre (umol/L) Standard Deviation 4.123
Total Bilirubin Values From Baseline Over Time Week 12	10.26 micromoles per litre (umol/L) Standard Deviation 4.758
Total Bilirubin Values From Baseline Over Time Week 24	10.41 micromoles per litre (umol/L) Standard Deviation 4.922
Total Bilirubin Values From Baseline Over Time Week 48	10.06 micromoles per litre (umol/L) Standard Deviation 4.503
Total Bilirubin Values From Baseline Over Time Week 72	8.82 micromoles per litre (umol/L) Standard Deviation 3.770

SECONDARY outcome

Timeframe: Up to week 72

Population: SAF (All participants who received any study drug); Here, "Number Analyzed" = Number of participants evaluable at that timepoint

Outcome measures

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 Participants All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Change From Baseline in Total Bilirubin Over Time Week 8	-0.37 umol/L Standard Deviation 3.120
Change From Baseline in Total Bilirubin Over Time Week 12	-0.44 umol/L Standard Deviation 3.854
Change From Baseline in Total Bilirubin Over Time Week 72	0.71 umol/L Standard Deviation 2.152
Change From Baseline in Total Bilirubin Over Time Week 24	-0.48 umol/L Standard Deviation 3.962
Change From Baseline in Total Bilirubin Over Time Week 48	-0.05 umol/L Standard Deviation 3.991

Adverse Events

Alirocumab 75 Q2W/Up150 Q2W

Serious events: 89 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Measure	Alirocumab 75 Q2W/Up150 Q2W n=1385 participants at risk All participants initiated treatment with PRALUENT (alirocumab) at the starting dose of 75 milligrams (mg) once every 2 weeks (Q2W). After week 8, the dose could be adjusted (up to 150 mg Q2W, maintained or from 150 mg Q2W to 75 mg Q2W) if needed based on low-density lipoprotein cholesterol (LDL-C) levels.
Injury, poisoning and procedural complications Electric shock	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Fall	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Angina unstable	0.72% 10/1385 • Number of events 10 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Angina pectoris	0.58% 8/1385 • Number of events 8 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Atrial fibrillation	0.43% 6/1385 • Number of events 6 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Acute myocardial infarction	0.36% 5/1385 • Number of events 5 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Acute left ventricular failure	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardiac failure congestive	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Coronary artery disease	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Arrhythmia	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardiac failure	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardiac failure acute	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardiac failure chronic	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardio-respiratory arrest	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Cardiovascular insufficiency	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Myocardial infarction	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Cardiac disorders Myocardial ischaemia	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Pneumonia	0.29% 4/1385 • Number of events 4 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Abscess limb	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Appendiceal abscess	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Appendicitis perforated	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Bronchitis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Cellulitis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Cholecystitis infective	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Cystitis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Diverticulitis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Pneumonia staphylococcal	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Infections and infestations Pyelonephritis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Cerebrovascular accident	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Ischaemic stroke	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Carotid artery disease	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Carotid artery occlusion	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Encephalopathy	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Nervous system disorders Haemorrhagic transformation stroke	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
General disorders Chest pain	0.22% 3/1385 • Number of events 3 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
General disorders Death	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
General disorders Non-cardiac chest pain	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Arterial injury	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Cartilage injury	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Concussion	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Femur fracture	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Lower limb fracture	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Injury, poisoning and procedural complications Traumatic haemorrhage	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Synovial sarcoma	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Respiratory, thoracic and mediastinal disorders Paranasal cyst	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Vascular disorders Hypertension	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Vascular disorders Hypertensive crisis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Vascular disorders Hypertensive urgency	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Vascular disorders Orthostatic hypotension	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Vascular disorders Peripheral artery occlusion	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Gastrointestinal disorders Intestinal ischaemia	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Gastrointestinal disorders Pancreatitis	0.07% 1/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Gastrointestinal disorders Pancreatitis chronic	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Gastrointestinal disorders Umbilical hernia	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Metabolism and nutrition disorders Hypomagnesaemia	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Musculoskeletal and connective tissue disorders Muscle spasms	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Renal and urinary disorders Nephrolithiasis	0.14% 2/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Renal and urinary disorders Ureterolithiasis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Skin and subcutaneous tissue disorders Diabetic foot	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Skin and subcutaneous tissue disorders Urticaria	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Eye disorders Cataract	0.07% 1/1385 • Number of events 2 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Hepatobiliary disorders Cholelithiasis	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Psychiatric disorders Bipolar disorder	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).
Reproductive system and breast disorders Uterine polyp	0.07% 1/1385 • Number of events 1 • Adverse events were recorded from the time of signed informed consent until the end of study, up to 80 weeks. Treatment-emergent adverse events (TEAEs) are reported. TEAEs are AEs that developed or worsened or became serious during the TEAE period (time from first dose of study drug to the last study visit).

Other adverse events

Adverse event data not reported

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER