Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin)

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02585778
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 517
• Locations: 110
• Arms: 2
• Actual Duration (Months): 17.3
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Primary Objectives:

• To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.

• To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin.

Secondary Objective:

To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol [non-HDL-C], apolipoprotein B [Apo B], total cholesterol [TC], lipoprotein a [Lp(a)], high density lipoprotein cholesterol [HDL-C], triglyceride [TG] levels, triglyceride rich lipoproteins [TGRL], apolipoprotein A-1 [Apo A-1], apolipoprotein C-III [Apo C-III], and LDL particle number and size).

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolaemia	Drug: Alirocumab; Drug: Placebo; Drug: Lipid-Modifying Therapy (LMT); Drug: Antihyperglycemic Drug	Phase 3

Detailed Description

The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 517 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Insulin Treated Patients With Type 1 or Type 2 Diabetes and With Hypercholesterolemia at High Cardiovascular Risk Not Adequately Controlled on Maximally Tolerated LDL-C Lowering Therapy
• Actual Study Start Date: Oct 23, 2015
• Actual Primary Completion Date: Apr 3, 2017
• Actual Study Completion Date: Apr 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Drug: Alirocumab; Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.; Other Names: Praluent SAR236553 REGN727 ; Drug: Lipid-Modifying Therapy (LMT); Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.; Drug: Antihyperglycemic Drug; Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.
Placebo Comparator: Placebo Q2W Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Drug: Placebo; Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.; Drug: Lipid-Modifying Therapy (LMT); Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.; Drug: Antihyperglycemic Drug; Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.

Outcome Measures

Primary Outcome Measures

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

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

2. Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) [From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)]

   Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Secondary Outcome Measures

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

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

2. Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis [From Baseline to Week 24]

   Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

3. Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis [From Baseline to Week 24]

   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.

4. Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis [From Baseline to Week 24]

   Measured LDL-C values via beta quantification method. 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.

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

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

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

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

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

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

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

   Adjusted percentages at Week 24 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).

9. Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis [Up to Week 24]

   Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach (for T1DM participants) and multiple imputation approach model (for T2DM participants) including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). The maximum likelihood estimate did not exist as response rate was zero in a treatment group of T1DM participants.

10. Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis [Up to Week 24]

    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).

11. Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis [Up to Week 24]

    Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

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

    Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach for handling of missing data followed by robust regression model. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

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

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

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

    Adjusted means and standard errors at Week 24 from multiple imputation approach for handling of missing data followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

15. Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis [From Baseline to Week 24]

    LDL-C particle number was calculated from lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy. 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.

16. Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis [From Baseline to Week 24]

    LDL-C particle size was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

17. Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis [Baseline, Weeks 12 and 24]

    Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

18. Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis [Baseline, Weeks 12 and 24]

    Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

19. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis [Baseline, Weeks 12 and 24]

    Absolute change = FPG value at specified weeks minus FPG value at baseline.

20. Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis [Baseline, Weeks 12 and 24]

    Absolute change = FPG value at specified weeks minus FPG value at baseline.

21. Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis [Baseline, Weeks 12 and 24]

    Absolute change = total daily insulin dose at specified weeks minus baseline value.

22. Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis [Baseline, Weeks 12 and 24]

    Absolute change = total daily insulin dose at specified weeks minus baseline value.

23. Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis [Baseline, Weeks 12 and 24]

    Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

24. Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis [Baseline, Weeks 12 and 24]

    Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

25. Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis [Baseline, Weeks 12 and 24]

    Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.

26. Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis [Baseline, Weeks 12 and 24]

    Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Participants diagnosed with Type 1 or Type 2 diabetes at least one year prior to the screening visit (Week -3).

• Signed written informed consent

• Participants with type 1 or type 2 diabetes treated with insulin whose LDL-C levels were not adequately controlled with maximally tolerated lipid-modifying therapy

• LDL-C of 70 mg/dL or greater

• 18 years of age or more

• Glycosylated hemoglobin (HbA1c) less than 10%

• History of cardiovascular disease (including coronary heart disease [CHD] and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor

Exclusion criteria:

• Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening or from screening to randomization, unless statin intolerant

• Triglycerides >400 mg/dL

• Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) equation

• Currently received or planned to receive renal replacement therapy (for example, hemodialysis)

• Change in weight of more than 5 kilograms within the prior 2 months

• Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or planned to intensify insulin regimen during the study

• Not treated with insulin for at least 6 months

• Planned to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study

• Body mass index (BMI) >45 kg/m² or planned to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study

• History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis)

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840020	Encino	California	United States	91436
2	Investigational Site Number 840002	Fresno	California	United States	93720
3	Investigational Site Number 840029	Oakland	California	United States	94612
4	Investigational Site Number 840027	Loveland	Colorado	United States	80538
5	Investigational Site Number 840026	Atlantis	Florida	United States	33462
6	Investigational Site Number 840006	Bradenton	Florida	United States	33180
7	Investigational Site Number 840023	Jacksonville	Florida	United States	32205
8	Investigational Site Number 840028	Palm Harbor	Florida	United States	34684
9	Investigational Site Number 840022	Ponte Vedra Beach	Florida	United States
10	Investigational Site Number 840021	Roswell	Georgia	United States	30076
11	Investigational Site Number 840007	Springfield	Illinois	United States	62704
12	Investigational Site Number 840011	Indianapolis	Indiana	United States	46260
13	Investigational Site Number 840015	Valparaiso	Indiana	United States	46383
14	Investigational Site Number 840010	Des Moines	Iowa	United States	50314
15	Investigational Site Number 840005	Louisville	Kentucky	United States
16	Investigational Site Number 840018	Auburn	Maine	United States	04210
17	Investigational Site Number 840013	Hyattsville	Maryland	United States	20782
18	Investigational Site Number 840016	Rockville	Maryland	United States	20852
19	Investigational Site Number 840004	Minneapolis	Minnesota	United States	55416
20	Investigational Site Number 840012	Jamaica	New York	United States	11432
21	Investigational Site Number 840014	Maumee	Ohio	United States	43537
22	Investigational Site Number 840009	Greer	South Carolina	United States	29651
23	Investigational Site Number 840024	Chattanooga	Tennessee	United States	37404
24	Investigational Site Number 840001	Austin	Texas	United States	78756
25	Investigational Site Number 840003	Dallas	Texas	United States	75230
26	Investigational Site Number 840019	Dallas	Texas	United States	75246
27	Investigational Site Number 840025	Houston	Texas	United States	77090
28	Investigational Site Number 840017	Ogden	Utah	United States	84405
29	Investigational Site Number 840008	Salt Lake City	Utah	United States	84102
30	Investigational Site Number 040002	Innsbruck		Austria	6020
31	Investigational Site Number 040005	Linz		Austria	4021
32	Investigational Site Number 040003	Salzburg		Austria	5020
33	Investigational Site Number 040004	Salzburg		Austria	5026
34	Investigational Site Number 040001	Wien		Austria	1160
35	Investigational Site Number 056002	Edegem		Belgium	2650
36	Investigational Site Number 056003	Haine-Saint-Paul		Belgium	7100
37	Investigational Site Number 056001	Leuven		Belgium	3000
38	Investigational Site Number 250-008	Besancon		France	25030
39	Investigational Site Number 250-005	Corbeil Essonnes		France	91100
40	Investigational Site Number 250-004	La Rochelle Cedex 1		France	17019
41	Investigational Site Number 250-003	Le Creusot		France	71200
42	Investigational Site Number 250-009	Mulhouse		France
43	Investigational Site Number 250-002	Nantes cedex 01		France	44093
44	Investigational Site Number 250-007	Paris		France	75018
45	Investigational Site Number 250-006	Strasbourg Cedex 2		France	67098
46	Investigational Site Number 250-001	TOULOUSE Cedex 9		France	31059
47	Investigational Site Number 276015	Aschaffenburg		Germany	63739
48	Investigational Site Number 276002	Berlin		Germany	10115
49	Investigational Site Number 276011	Dortmund		Germany	44137
50	Investigational Site Number 276019	Dresden		Germany	01099
51	Investigational Site Number 276014	Dresden		Germany	01279
52	Investigational Site Number 276009	Dresden		Germany	01307
53	Investigational Site Number 276021	Hamburg		Germany	20246
54	Investigational Site Number 276018	Hamburg		Germany	22041
55	Investigational Site Number 276005	Heidelberg		Germany	69115
56	Investigational Site Number 276013	Lüneburg		Germany	21339
57	Investigational Site Number 276022	Magdeburg		Germany	39120
58	Investigational Site Number 276008	Neumünster		Germany	24534
59	Investigational Site Number 276017	Neuwied		Germany	56564
60	Investigational Site Number 276004	Oldenburg		Germany	26133
61	Investigational Site Number 276003	Pirna		Germany	01796
62	Investigational Site Number 276006	Riesa		Germany	01587
63	Investigational Site Number 276010	Saarlouis		Germany	66740
64	Investigational Site Number 276016	Sulzbach-Rosenberg		Germany	92237
65	Investigational Site Number 380004	Catania		Italy	95122
66	Investigational Site Number 380003	Catanzaro		Italy
67	Investigational Site Number 380011	Como		Italy	22100
68	Investigational Site Number 380006	Milano		Italy	20132
69	Investigational Site Number 380007	Milano		Italy	20162
70	Investigational Site Number 380005	Moncalieri		Italy	10024
71	Investigational Site Number 380009	Napoli		Italy	80138
72	Investigational Site Number 380008	Padova		Italy
73	Investigational Site Number 380002	Palermo		Italy	90127
74	Investigational Site Number 380001	Pisa		Italy	56124
75	Investigational Site Number 380010	Roma		Italy	00133
76	Investigational Site Number 380012	Verona		Italy	37126
77	Investigational Site Number 528002	Apeldoorn		Netherlands	7334 DZ
78	Investigational Site Number 528005	Groningen		Netherlands
79	Investigational Site Number 528003	Hoogeveen		Netherlands	7909AA
80	Investigational Site Number 528001	Rotterdam		Netherlands	3045PM
81	Investigational Site Number 528004	Utrecht		Netherlands
82	Investigational Site Number 724007	Badalona		Spain	08915
83	Investigational Site Number 724001	Barcelona		Spain	08025
84	Investigational Site Number 724006	Ferrol		Spain	15405
85	Investigational Site Number 724013	Granada		Spain	18003
86	Investigational Site Number 724005	Madrid		Spain	28040
87	Investigational Site Number 724004	Madrid		Spain
88	Investigational Site Number 724011	Majadahonda		Spain	28222
89	Investigational Site Number 724008	Málaga		Spain	29010
90	Investigational Site Number 724014	Oviedo		Spain	33006
91	Investigational Site Number 724009	Palma de Mallorca		Spain	07198
92	Investigational Site Number 724002	Pamplona		Spain	31008
93	Investigational Site Number 724010	Sant Joan Despí		Spain	08970
94	Investigational Site Number 724012	Segovia		Spain
95	Investigational Site Number 724003	Sevilla		Spain	41071
96	Investigational Site Number 756001	Olten		Switzerland	4600
97	Investigational Site Number 756003	St. Gallen		Switzerland	9016
98	Investigational Site Number 826010	Airdrie		United Kingdom	ML60JS
99	Investigational Site Number 826011	Bath		United Kingdom	BA13NG
100	Investigational Site Number 826009	Bournemouth		United Kingdom	BH77DW
101	Investigational Site Number 826005	Bradford		United Kingdom	BD96RJ
102	Investigational Site Number 826004	Bristol		United Kingdom	BS28HW
103	Investigational Site Number 826001	Burton On Trent		United Kingdom	DE13 0RB
104	Investigational Site Number 826015	Durham		United Kingdom	DH15TW
105	Investigational Site Number 826012	High Wycombe		United Kingdom	HP112TT
106	Investigational Site Number 826007	Manchester		United Kingdom	M239LT
107	Investigational Site Number 826006	Peterborough		United Kingdom	PE39QZ
108	Investigational Site Number 826003	Southampton		United Kingdom	SO303JB
109	Investigational Site Number 826008	Truro		United Kingdom	TR13LJ
110	Investigational Site Number 826002	Welwyn Garden City		United Kingdom	AL74HQ

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Jul 8, 2015
• Statistical Analysis Plan - Mar 6, 2017

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02585778
• Other Study ID Numbers: LPS14355; 2015-000799-92; U1111-1172-4772
• First Posted: Oct 23, 2015
• Last Update Posted: May 17, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Hypercholesterolemia; Hypoglycemic Agents

Study Results

Participant Flow

Recruitment Details	The study was conducted at 103 sites in 10 countries. Of these, 97 active sites randomized at least 1 participant. Overall 796 participants were screened between October 2015 and August 2016, of whom 279 were screen failures. Screen failures were mainly due to exclusion criteria met or inclusion criteria not met.
Pre-assignment Detail	Randomization was stratified by diabetes type (Type 1 diabetes mellitus [T1DM] versus Type 2 diabetes mellitus [T2DM]). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 2:1 ratio (Alirocumab:Placebo). A total of 517 participants were randomized. Baseline and efficacy data were analyzed per stratum.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
Arm/Group Description	Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Period Title: Overall Study
STARTED	345	172
Treated (Safety Population)	344	170
ITT Population	336	167
mITT Population	333	164
T1DM Participants	51	25
T2DM Participants	294	147
COMPLETED	312	157
NOT COMPLETED	33	15

Baseline Characteristics

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Total of all reporting groups
Overall Participants	51	25	294	147	517
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (10.1)	58.5 (7.8)	63.9 (8.9)	64.0 (9.4)	62.8 (9.6)
Sex: Female, Male (Count of Participants)
Female	22 43.1%	8 32%	133 45.2%	69 46.9%	232 44.9%
Male	29 56.9%	17 68%	161 54.8%	78 53.1%	285 55.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2%	0 0%	13 4.4%	8 5.4%	22 4.3%
Not Hispanic or Latino	50 98%	25 100%	280 95.2%	138 93.9%	493 95.4%
Unknown or Not Reported	0 0%	0 0%	1 0.3%	1 0.7%	2 0.4%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	50 98%	24 96%	259 88.1%	135 91.8%	468 90.5%
Black	1 2%	0 0%	27 9.2%	7 4.8%	35 6.8%
Asian/Oriental	0 0%	0 0%	7 2.4%	3 2%	10 1.9%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Other	0 0%	1 4%	1 0.3%	2 1.4%	4 0.8%
Calculated LDL-C in mg/dL (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	126.4 (58.2)	110.2 (31.2)	110.8 (36.5)	109.6 (39.1)	112.0 (39.8)
Calculated LDL-C in mmol/L (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	3.273 (1.506)	2.853 (0.807)	2.871 (0.944)	2.838 (1.013)	2.900 (1.031)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Least Squares Mean (Standard Error) [percent change]	-51.8 (3.7)	-3.9 (5.3)	-48.2 (1.6)	0.8 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Alirocumab group was compared to placebo group using an appropriate contrast statement.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-47.8
	Confidence Interval	(2-Sided) 95%; -60.7 to -35.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Alirocumab group was compared to placebo group using an appropriate contrast statement.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-49.0
	Confidence Interval	(2-Sided) 95%; -54.4 to -43.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

2. Primary Outcome

Title	Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Time Frame	From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received at least one dose or part of a dose of a study drug (treated).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	344	170
Any AE	64.5 126.5%	64.1 256.4%
Any Serious AE	9.0 17.6%	9.4 37.6%
Any AE leading to death	0 0%	0.6 2.4%
Any AE leading to treatment discontinuation	4.9 9.6%	2.4 9.6%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Least Squares Mean (Standard Error) [percent change]	-53.8 (3.7)	-3.2 (5.3)	-50.9 (1.6)	0.7 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level. Hierarchical testing procedure was followed for T1DM and T2DM participants separately.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-50.6
	Confidence Interval	(2-Sided) 95%; -63.4 to -37.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-51.6
	Confidence Interval	(2-Sided) 95%; -56.9 to -46.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment (Measured LDL-C ITT population).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	47	22	277	139
Least Squares Mean (Standard Error) [percent change]	-49.4 (3.7)	-1.1 (5.4)	-43.3 (1.6)	2.4 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-48.4
	Confidence Interval	(2-Sided) 95%; -61.2 to -35.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-45.7
	Confidence Interval	(2-Sided) 95%; -50.9 to -40.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Description	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.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment at Week 12 (ITT population at Week 12).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	284	140
Least Squares Mean (Standard Error) [percent change]	-49.4 (3.5)	-4.5 (5.0)	-48.8 (1.4)	1.4 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-44.8
	Confidence Interval	(2-Sided) 95%; -56.9 to -32.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-50.2
	Confidence Interval	(2-Sided) 95%; -55.2 to -45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

6. Secondary Outcome

Title	Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis
Description	Measured LDL-C values via beta quantification method. 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.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment at Week 12 (Measured LDL-C ITT population at Week 12).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	45	22	275	136
Least Squares Mean (Standard Error) [percent change]	-46.7 (3.6)	-4.0 (5.1)	-44.8 (1.4)	-0.8 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-42.7
	Confidence Interval	(2-Sided) 95%; -54.9 to -30.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-44.1
	Confidence Interval	(2-Sided) 95%; -49.0 to -39.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Least Squares Mean (Standard Error) [percent change]	-45.9 (3.3)	-3.2 (4.8)	-37.9 (1.4)	0.7 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-42.7
	Confidence Interval	(2-Sided) 95%; -54.2 to -31.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-38.7
	Confidence Interval	(2-Sided) 95%; -43.4 to -33.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	47	22	279	140
Least Squares Mean (Standard Error) [percent change]	-39.4 (3.0)	-0.4 (4.3)	-33.4 (1.3)	3.3 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-39.0
	Confidence Interval	(2-Sided) 95%; -49.4 to -28.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-36.7
	Confidence Interval	(2-Sided) 95%; -40.9 to -32.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment (Total-C ITT population).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Least Squares Mean (Standard Error) [percent change]	-29.9 (2.5)	-0.7 (3.6)	-26.8 (1.0)	0.8 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-29.2
	Confidence Interval	(2-Sided) 95%; -37.8 to -20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-27.6
	Confidence Interval	(2-Sided) 95%; -31.2 to -24.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

10. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 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).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Number [percentage of participants]	70.2 137.6%	5.1 20.4%	76.4 26%	7.4 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	117.0
	Confidence Interval	(2-Sided) 95%; 13.1 to 1041.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	84.6
	Confidence Interval	(2-Sided) 95%; 36.5 to 196.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

11. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach (for T1DM participants) and multiple imputation approach model (for T2DM participants) including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). The maximum likelihood estimate did not exist as response rate was zero in a treatment group of T1DM participants.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Number [percentage of participants]	55.1 108%	0 0%	50.7 17.2%	2.7 1.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	52.9
	Confidence Interval	(2-Sided) 95%; 16.6 to 168.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

12. Secondary Outcome

Title	Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis
Description	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).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Number [percentage of participants]	79.0 154.9%	22.9 91.6%	70.9 24.1%	13.8 9.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	33.2
	Confidence Interval	(2-Sided) 95%; 8.0 to 137.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	27.1
	Confidence Interval	(2-Sided) 95%; 14.2 to 51.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

13. Secondary Outcome

Title	Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis
Description	Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Non-HDL-C mITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Number [percentage of participants]	59.6 116.9%	5.3 21.2%	52.3 17.8%	1.7 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	55.5
	Confidence Interval	(2-Sided) 95%; 6.5 to 473.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Logistic
	Comments	Multiple imputation approach followed by logistic regression model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	103.3
	Confidence Interval	(2-Sided) 95%; 24.6 to 433.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

14. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Description	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach for handling of missing data followed by robust regression model. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Mean (Standard Error) [percent change]	-23.0 (3.8)	-4.3 (5.3)	-19.0 (1.6)	-0.5 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-18.7
	Confidence Interval	(2-Sided) 95%; -31.4 to -6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-18.4
	Confidence Interval	(2-Sided) 95%; -23.7 to -13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Least Squares Mean (Standard Error) [percent change]	11.2 (2.4)	7.3 (3.5)	8.1 (1.0)	3.7 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants, Placebo Q2W: T1DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3434
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -4.2 to 12.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0100
	Comments	Threshold for significance at 0.05 level.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95%; 1.1 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

16. Secondary Outcome

Title	Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Description	Adjusted means and standard errors at Week 24 from multiple imputation approach for handling of missing data followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Mean (Standard Error) [percent change]	-13.6 (4.7)	1.9 (6.7)	-5.7 (2.0)	0.0 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants, Placebo Q2W: T2DM Participants
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant in relevant diabetes stratum).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0902
	Comments	Threshold for significance at 0.05 level.
	Method	Regression, Robust
	Comments	Multiple imputation approach followed by robust regression model.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-5.7
	Confidence Interval	(2-Sided) 95%; -12.3 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Alirocumab vs. Placebo

17. Secondary Outcome

Title	Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis
Description	LDL-C particle number was calculated from lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline LDL-C particle number value on- or off-treatment (LDL-C particle number ITT population).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	45	22	272	134
Least Squares Mean (Standard Error) [percent change]	-44.4 (3.2)	-4.4 (4.6)	-38.3 (1.3)	1.9 (1.9)

18. Secondary Outcome

Title	Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis
Description	LDL-C particle size was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants of the ITT population with one baseline and at least one post-baseline LDL-C particle size value on- or off-treatment (LDL-C particle size ITT population).

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	44	22	267	134
Least Squares Mean (Standard Error) [percent change]	-2.3 (0.3)	0.8 (0.5)	-2.8 (0.1)	-0.3 (0.2)

19. Secondary Outcome

Title	Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis
Description	Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Change at Week 12	0.00 (0.46)	-0.22 (0.39)	-0.04 (0.57)	0.00 (0.58)
Change at Week 24	-0.03 (0.60)	-0.23 (0.36)	0.18 (0.74)	0.06 (0.66)

20. Secondary Outcome

Title	Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis
Description	Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Change at Week 12	0.00 (0.46)	-0.22 (0.39)	-0.04 (0.57)	0.00 (0.59)
Change at Week 24	-0.05 (0.61)	-0.27 (0.34)	0.18 (0.74)	0.06 (0.67)

21. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis
Description	Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Change at Week 12	0.23 (4.44)	0.45 (4.73)	0.25 (2.73)	0.13 (2.73)
Change at Week 24	0.52 (5.20)	0.81 (4.21)	0.52 (3.43)	0.55 (2.62)

22. Secondary Outcome

Title	Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis
Description	Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Change at Week 12	0.23 (4.44)	0.45 (4.73)	0.22 (2.70)	0.15 (2.74)
Change at Week 24	0.38 (5.24)	0.71 (4.19)	0.52 (3.47)	0.48 (2.53)

23. Secondary Outcome

Title	Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis
Description	Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population . Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Change at Week 12	-10.0 (48.7)	-1.3 (9.6)	0.2 (7.9)	1.4 (11.4)
Change at Week 24	-2.2 (11.3)	-0.8 (9.8)	2.2 (14.8)	1.6 (11.4)

24. Secondary Outcome

Title	Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis
Description	Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Change at Week 12	-10.0 (48.7)	-1.3 (9.6)	0.2 (7.9)	1.4 (11.4)
Change at Week 24	-2.2 (11.3)	-0.8 (9.8)	1.7 (11.7)	1.6 (11.5)

25. Secondary Outcome

Title	Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis
Description	Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population . Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Change at Week 12	-0.1 (0.5)	0.0 (0.1)	0.0 (0.1)	0.0 (0.1)
Change at Week 24	0.0 (0.1)	0.0 (0.1)	0.0 (0.2)	0.0 (0.1)

26. Secondary Outcome

Title	Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis
Description	Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Change at Week 12	-0.1 (0.5)	0.0 (0.1)	0.0 (0.1)	0.0 (0.1)
Change at Week 24	0.0 (0.1)	0.0 (0.1)	0.0 (0.1)	0.0 (0.1)

27. Secondary Outcome

Title	Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis
Description	Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	25	287	142
Change at Week 12	0 (0)	0 (0)	0 (0.1)	0 (0.2)
Change at Week 24	0 (0)	0 (0)	0 (0.3)	0 (0.2)

28. Secondary Outcome

Title	Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis
Description	Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Measure Participants	49	24	284	140
Change at Week 12	0 (0)	0 (0)	0 (0.1)	0 (0.2)
Change at Week 24	0 (0)	0 (0)	0 (0.3)	0 (0.2)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to final visit (Week 32) in the study regardless of seriousness or relationship to study drugs.
Adverse Event Reporting Description	Reported AEs and deaths are TEAEs that is AEs that developed/worsened and death that occurred during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W		Placebo Q2W
Arm/Group Description	Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.		Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
All Cause Mortality
	Alirocumab 75 mg Q2W/Up to 150 mg Q2W		Placebo Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/344 (0%)		1/170 (0.6%)
Serious Adverse Events
	Alirocumab 75 mg Q2W/Up to 150 mg Q2W		Placebo Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/344 (9%)		16/170 (9.4%)
Blood and lymphatic system disorders
Eosinophilia	1/344 (0.3%)		0/170 (0%)
Lymphadenopathy	0/344 (0%)		1/170 (0.6%)
Cardiac disorders
Acute myocardial infarction	0/344 (0%)		1/170 (0.6%)
Angina pectoris	1/344 (0.3%)		0/170 (0%)
Angina unstable	1/344 (0.3%)		1/170 (0.6%)
Aortic valve stenosis	0/344 (0%)		1/170 (0.6%)
Cardiac failure	1/344 (0.3%)		0/170 (0%)
Coronary artery disease	1/344 (0.3%)		0/170 (0%)
Coronary artery occlusion	1/344 (0.3%)		0/170 (0%)
Ischaemic cardiomyopathy	0/344 (0%)		1/170 (0.6%)
Myocardial infarction	0/344 (0%)		1/170 (0.6%)
Eye disorders
Diplopia	0/344 (0%)		1/170 (0.6%)
Vitreous haemorrhage	1/344 (0.3%)		0/170 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/344 (0%)		1/170 (0.6%)
Intestinal haemorrhage	0/344 (0%)		1/170 (0.6%)
General disorders
Influenza like illness	1/344 (0.3%)		0/170 (0%)
Non-cardiac chest pain	1/344 (0.3%)		0/170 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/344 (0%)		1/170 (0.6%)
Immune system disorders
Drug hypersensitivity	1/344 (0.3%)		0/170 (0%)
Infections and infestations
Bronchitis	1/344 (0.3%)		0/170 (0%)
Campylobacter gastroenteritis	0/344 (0%)		1/170 (0.6%)
Diabetic foot infection	1/344 (0.3%)		0/170 (0%)
Endometritis	1/344 (0.3%)		0/170 (0%)
Osteomyelitis	1/344 (0.3%)		0/170 (0%)
Pneumonia	1/344 (0.3%)		2/170 (1.2%)
Pyelonephritis acute	1/344 (0.3%)		0/170 (0%)
Urinary tract infection	2/344 (0.6%)		0/170 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/344 (0.3%)		0/170 (0%)
Procedural hypotension	0/344 (0%)		1/170 (0.6%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/344 (0.3%)		0/170 (0%)
Mixed connective tissue disease	1/344 (0.3%)		0/170 (0%)
Musculoskeletal chest pain	1/344 (0.3%)		0/170 (0%)
Osteoarthritis	1/344 (0.3%)		0/170 (0%)
Osteochondrosis	1/344 (0.3%)		0/170 (0%)
Spondylolisthesis	0/344 (0%)		1/170 (0.6%)
Vertebral foraminal stenosis	2/344 (0.6%)		0/170 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/344 (0.3%)		0/170 (0%)
Basal cell carcinoma	1/344 (0.3%)		0/170 (0%)
Bowen's disease	1/344 (0.3%)		0/170 (0%)
Lung cancer metastatic	1/344 (0.3%)		0/170 (0%)
Prostate cancer	1/344 (0.3%)		0/170 (0%)
Squamous cell carcinoma of skin	1/344 (0.3%)		0/170 (0%)
Nervous system disorders
Amnesia	1/344 (0.3%)		0/170 (0%)
Carotid arteriosclerosis	1/344 (0.3%)		0/170 (0%)
Cerebral infarction	0/344 (0%)		1/170 (0.6%)
Pseudoradicular syndrome	0/344 (0%)		1/170 (0.6%)
Radicular syndrome	0/344 (0%)		1/170 (0.6%)
Syncope	1/344 (0.3%)		0/170 (0%)
Transient ischaemic attack	1/344 (0.3%)		0/170 (0%)
Renal and urinary disorders
Hydronephrosis	1/344 (0.3%)		0/170 (0%)
Renal failure	1/344 (0.3%)		0/170 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/344 (0.3%)		0/170 (0%)
Dyspnoea	0/344 (0%)		1/170 (0.6%)
Vascular disorders
Deep vein thrombosis	0/344 (0%)		1/170 (0.6%)
Peripheral arterial occlusive disease	1/344 (0.3%)		0/170 (0%)
Other (Not Including Serious) Adverse Events
	Alirocumab 75 mg Q2W/Up to 150 mg Q2W		Placebo Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/344 (4.9%)		9/170 (5.3%)
Infections and infestations
Nasopharyngitis	17/344 (4.9%)		9/170 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.