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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)

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ClinicalTrials.gov Identifier: NCT02585778
Recruitment Status : Completed
First Posted : October 23, 2015
Results First Posted : May 17, 2018
Last Update Posted : May 17, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hypercholesterolaemia
Interventions Drug: Alirocumab
Drug: Placebo
Drug: Lipid-Modifying Therapy (LMT)
Drug: Antihyperglycemic Drug
Enrollment 517
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 Details 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
Hide 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 [1] 172 [1]
Treated (Safety Population) 344 170
ITT Population 336 167
mITT Population 333 164
T1DM Participants [2] 51 25
T2DM Participants [3] 294 147
Completed [4] 312 157
Not Completed 33 15
Reason Not Completed
Adverse Event             17             4
Participant did not wish to continue             9             4
Poor compliance to study protocol             0             2
Death             0             1
Randomized but not treated             1             2
Other than specified above             6             2
[1]
Randomized
[2]
Randomized stratum: T1DM
[3]
Randomized stratum: T2DM
[4]
Completed = treatment completion
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
Hide 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 Number of Baseline Participants 51 25 294 147 517
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
54.9  (10.1) 58.5  (7.8) 63.9  (8.9) 64.0  (9.4) 62.8  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
Female
22
  43.1%
8
  32.0%
133
  45.2%
69
  46.9%
232
  44.9%
Male
29
  56.9%
17
  68.0%
161
  54.8%
78
  53.1%
285
  55.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
Hispanic or Latino
1
   2.0%
0
   0.0%
13
   4.4%
8
   5.4%
22
   4.3%
Not Hispanic or Latino
50
  98.0%
25
 100.0%
280
  95.2%
138
  93.9%
493
  95.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   0.3%
1
   0.7%
2
   0.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
White/Caucasian
50
  98.0%
24
  96.0%
259
  88.1%
135
  91.8%
468
  90.5%
Black
1
   2.0%
0
   0.0%
27
   9.2%
7
   4.8%
35
   6.8%
Asian/Oriental
0
   0.0%
0
   0.0%
7
   2.4%
3
   2.0%
10
   1.9%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
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
   0.0%
0
   0.0%
Other
0
   0.0%
1
   4.0%
1
   0.3%
2
   1.4%
4
   0.8%
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
126.4  (58.2) 110.2  (31.2) 110.8  (36.5) 109.6  (39.1) 112.0  (39.8)
[1]
Measure Description: Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - high density lipoprotein [HDL] cholesterol - [Triglyceride/5]).
Calculated LDL-C in mmol/L   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 51 participants 25 participants 294 participants 147 participants 517 participants
3.273  (1.506) 2.853  (0.807) 2.871  (0.944) 2.838  (1.013) 2.900  (1.031)
[1]
Measure Description: Calculated LDL-C in mmol/L from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/2.2]).
1.Primary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-51.8  (3.7) -3.9  (5.3) -48.2  (1.6) 0.8  (2.2)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -47.8
Confidence Interval (2-Sided) 95%
-60.7 to -35.0
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -49.0
Confidence Interval (2-Sided) 95%
-54.4 to -43.6
Estimation Comments Alirocumab vs. Placebo
2.Primary Outcome
Title Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 344 170
Measure Type: Number
Unit of Measure: percentage of participants
Any AE 64.5 64.1
Any Serious AE 9.0 9.4
Any AE leading to death 0 0.6
Any AE leading to treatment discontinuation 4.9 2.4
3.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-53.8  (3.7) -3.2  (5.3) -50.9  (1.6) 0.7  (2.2)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -50.6
Confidence Interval (2-Sided) 95%
-63.4 to -37.9
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -51.6
Confidence Interval (2-Sided) 95%
-56.9 to -46.4
Estimation Comments Alirocumab vs. Placebo
4.Secondary Outcome
Title Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 47 22 277 139
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-49.4  (3.7) -1.1  (5.4) -43.3  (1.6) 2.4  (2.2)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -48.4
Confidence Interval (2-Sided) 95%
-61.2 to -35.5
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -45.7
Confidence Interval (2-Sided) 95%
-50.9 to -40.4
Estimation Comments Alirocumab vs. Placebo
5.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 284 140
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-49.4  (3.5) -4.5  (5.0) -48.8  (1.4) 1.4  (2.1)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -44.8
Confidence Interval (2-Sided) 95%
-56.9 to -32.8
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -50.2
Confidence Interval (2-Sided) 95%
-55.2 to -45.3
Estimation Comments Alirocumab vs. Placebo
6.Secondary Outcome
Title Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 45 22 275 136
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-46.7  (3.6) -4.0  (5.1) -44.8  (1.4) -0.8  (2.0)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -42.7
Confidence Interval (2-Sided) 95%
-54.9 to -30.5
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -44.1
Confidence Interval (2-Sided) 95%
-49.0 to -39.2
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-45.9  (3.3) -3.2  (4.8) -37.9  (1.4) 0.7  (2.0)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -42.7
Confidence Interval (2-Sided) 95%
-54.2 to -31.3
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -38.7
Confidence Interval (2-Sided) 95%
-43.4 to -33.9
Estimation Comments Alirocumab vs. Placebo
8.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 47 22 279 140
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-39.4  (3.0) -0.4  (4.3) -33.4  (1.3) 3.3  (1.7)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -39.0
Confidence Interval (2-Sided) 95%
-49.4 to -28.7
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -36.7
Confidence Interval (2-Sided) 95%
-40.9 to -32.5
Estimation Comments Alirocumab vs. Placebo
9.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-29.9  (2.5) -0.7  (3.6) -26.8  (1.0) 0.8  (1.5)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.2
Confidence Interval (2-Sided) 95%
-37.8 to -20.7
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -27.6
Confidence Interval (2-Sided) 95%
-31.2 to -24.1
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Measure Type: Number
Unit of Measure: percentage of participants
70.2 5.1 76.4 7.4
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
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
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Measure Type: Number
Unit of Measure: percentage of participants
55.1 0 50.7 2.7
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Measure Type: Number
Unit of Measure: percentage of participants
79.0 22.9 70.9 13.8
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
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
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Measure Type: Number
Unit of Measure: percentage of participants
59.6 5.3 52.3 1.7
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
14.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Error)
Unit of Measure: percent change
-23.0  (3.8) -4.3  (5.3) -19.0  (1.6) -0.5  (2.2)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
15.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Least Squares Mean (Standard Error)
Unit of Measure: percent change
11.2  (2.4) 7.3  (3.5) 8.1  (1.0) 3.7  (1.4)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.3434
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-4.2 to 12.0
Estimation Comments Alirocumab vs. Placebo
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0100
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.4
Confidence Interval (2-Sided) 95%
1.1 to 7.7
Estimation Comments Alirocumab vs. Placebo
16.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Error)
Unit of Measure: percent change
-13.6  (4.7) 1.9  (6.7) -5.7  (2.0) 0.0  (2.7)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments Alirocumab vs. Placebo
17.Secondary Outcome
Title Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 45 22 272 134
Least Squares Mean (Standard Error)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 44 22 267 134
Least Squares Mean (Standard Error)
Unit of Measure: 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
Hide Description Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Deviation)
Unit of Measure: percentage of hemoglobin
Change at Week 12 Number Analyzed 48 participants 22 participants 281 participants 138 participants
0.00  (0.46) -0.22  (0.39) -0.04  (0.57) 0.00  (0.58)
Change at Week 24 Number Analyzed 47 participants 22 participants 261 participants 135 participants
-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
Hide Description Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Mean (Standard Deviation)
Unit of Measure: percentage of hemoglobin
Change at Week 12 Number Analyzed 48 participants 22 participants 275 participants 136 participants
0.00  (0.46) -0.22  (0.39) -0.04  (0.57) 0.00  (0.59)
Change at Week 24 Number Analyzed 43 participants 20 participants 243 participants 129 participants
-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
Hide Description Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Deviation)
Unit of Measure: mmol/L
Change at Week 12 Number Analyzed 46 participants 20 participants 278 participants 138 participants
0.23  (4.44) 0.45  (4.73) 0.25  (2.73) 0.13  (2.73)
Change at Week 24 Number Analyzed 46 participants 22 participants 257 participants 135 participants
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
Hide Description Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Mean (Standard Deviation)
Unit of Measure: mmol/L
Change at Week 12 Number Analyzed 46 participants 20 participants 272 participants 136 participants
0.23  (4.44) 0.45  (4.73) 0.22  (2.70) 0.15  (2.74)
Change at Week 24 Number Analyzed 42 participants 20 participants 240 participants 129 participants
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
Hide Description Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Deviation)
Unit of Measure: units (U)
Change at Week 12 Number Analyzed 47 participants 21 participants 279 participants 136 participants
-10.0  (48.7) -1.3  (9.6) 0.2  (7.9) 1.4  (11.4)
Change at Week 24 Number Analyzed 48 participants 23 participants 258 participants 130 participants
-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
Hide Description Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Mean (Standard Deviation)
Unit of Measure: units (U)
Change at Week 12 Number Analyzed 47 participants 21 participants 278 participants 135 participants
-10.0  (48.7) -1.3  (9.6) 0.2  (7.9) 1.4  (11.4)
Change at Week 24 Number Analyzed 48 participants 23 participants 257 participants 129 participants
-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
Hide Description Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Deviation)
Unit of Measure: U/kg
Change at Week 12 Number Analyzed 47 participants 21 participants 279 participants 136 participants
-0.1  (0.5) 0.0  (0.1) 0.0  (0.1) 0.0  (0.1)
Change at Week 24 Number Analyzed 48 participants 23 participants 258 participants 130 participants
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
Hide Description Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Mean (Standard Deviation)
Unit of Measure: U/kg
Change at Week 12 Number Analyzed 47 participants 21 participants 278 participants 135 participants
-0.1  (0.5) 0.0  (0.1) 0.0  (0.1) 0.0  (0.1)
Change at Week 24 Number Analyzed 48 participants 23 participants 257 participants 129 participants
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 25 287 142
Mean (Standard Deviation)
Unit of Measure: glucose lowering treatments
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 49 24 284 140
Mean (Standard Deviation)
Unit of Measure: glucose lowering treatments
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)
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
Hide 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 (%) Affected / at Risk (%)
Total   0/344 (0.00%)   1/170 (0.59%) 
Show Serious Adverse Events Hide Serious Adverse Events
Alirocumab 75 mg Q2W/Up to 150 mg Q2W Placebo Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   31/344 (9.01%)   16/170 (9.41%) 
Blood and lymphatic system disorders     
Eosinophilia  1  1/344 (0.29%)  0/170 (0.00%) 
Lymphadenopathy  1  0/344 (0.00%)  1/170 (0.59%) 
Cardiac disorders     
Acute myocardial infarction  1  0/344 (0.00%)  1/170 (0.59%) 
Angina pectoris  1  1/344 (0.29%)  0/170 (0.00%) 
Angina unstable  1  1/344 (0.29%)  1/170 (0.59%) 
Aortic valve stenosis  1  0/344 (0.00%)  1/170 (0.59%) 
Cardiac failure  1  1/344 (0.29%)  0/170 (0.00%) 
Coronary artery disease  1  1/344 (0.29%)  0/170 (0.00%) 
Coronary artery occlusion  1  1/344 (0.29%)  0/170 (0.00%) 
Ischaemic cardiomyopathy  1  0/344 (0.00%)  1/170 (0.59%) 
Myocardial infarction  1  0/344 (0.00%)  1/170 (0.59%) 
Eye disorders     
Diplopia  1  0/344 (0.00%)  1/170 (0.59%) 
Vitreous haemorrhage  1  1/344 (0.29%)  0/170 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  0/344 (0.00%)  1/170 (0.59%) 
Intestinal haemorrhage  1  0/344 (0.00%)  1/170 (0.59%) 
General disorders     
Influenza like illness  1  1/344 (0.29%)  0/170 (0.00%) 
Non-cardiac chest pain  1  1/344 (0.29%)  0/170 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/344 (0.00%)  1/170 (0.59%) 
Immune system disorders     
Drug hypersensitivity  1  1/344 (0.29%)  0/170 (0.00%) 
Infections and infestations     
Bronchitis  1  1/344 (0.29%)  0/170 (0.00%) 
Campylobacter gastroenteritis  1  0/344 (0.00%)  1/170 (0.59%) 
Diabetic foot infection  1  1/344 (0.29%)  0/170 (0.00%) 
Endometritis  1  1/344 (0.29%)  0/170 (0.00%) 
Osteomyelitis  1  1/344 (0.29%)  0/170 (0.00%) 
Pneumonia  1  1/344 (0.29%)  2/170 (1.18%) 
Pyelonephritis acute  1  1/344 (0.29%)  0/170 (0.00%) 
Urinary tract infection  1  2/344 (0.58%)  0/170 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/344 (0.29%)  0/170 (0.00%) 
Procedural hypotension  1  0/344 (0.00%)  1/170 (0.59%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/344 (0.29%)  0/170 (0.00%) 
Mixed connective tissue disease  1  1/344 (0.29%)  0/170 (0.00%) 
Musculoskeletal chest pain  1  1/344 (0.29%)  0/170 (0.00%) 
Osteoarthritis  1  1/344 (0.29%)  0/170 (0.00%) 
Osteochondrosis  1  1/344 (0.29%)  0/170 (0.00%) 
Spondylolisthesis  1  0/344 (0.00%)  1/170 (0.59%) 
Vertebral foraminal stenosis  1  2/344 (0.58%)  0/170 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma pancreas  1  1/344 (0.29%)  0/170 (0.00%) 
Basal cell carcinoma  1  1/344 (0.29%)  0/170 (0.00%) 
Bowen's disease  1  1/344 (0.29%)  0/170 (0.00%) 
Lung cancer metastatic  1  1/344 (0.29%)  0/170 (0.00%) 
Prostate cancer  1  1/344 (0.29%)  0/170 (0.00%) 
Squamous cell carcinoma of skin  1  1/344 (0.29%)  0/170 (0.00%) 
Nervous system disorders     
Amnesia  1  1/344 (0.29%)  0/170 (0.00%) 
Carotid arteriosclerosis  1  1/344 (0.29%)  0/170 (0.00%) 
Cerebral infarction  1  0/344 (0.00%)  1/170 (0.59%) 
Pseudoradicular syndrome  1  0/344 (0.00%)  1/170 (0.59%) 
Radicular syndrome  1  0/344 (0.00%)  1/170 (0.59%) 
Syncope  1  1/344 (0.29%)  0/170 (0.00%) 
Transient ischaemic attack  1  1/344 (0.29%)  0/170 (0.00%) 
Renal and urinary disorders     
Hydronephrosis  1  1/344 (0.29%)  0/170 (0.00%) 
Renal failure  1  1/344 (0.29%)  0/170 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/344 (0.29%)  0/170 (0.00%) 
Dyspnoea  1  0/344 (0.00%)  1/170 (0.59%) 
Vascular disorders     
Deep vein thrombosis  1  0/344 (0.00%)  1/170 (0.59%) 
Peripheral arterial occlusive disease  1  1/344 (0.29%)  0/170 (0.00%) 
1
Term from vocabulary, MedDra 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alirocumab 75 mg Q2W/Up to 150 mg Q2W Placebo Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   17/344 (4.94%)   9/170 (5.29%) 
Infections and infestations     
Nasopharyngitis  1  17/344 (4.94%)  9/170 (5.29%) 
1
Term from vocabulary, MedDra 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 1#
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02585778     History of Changes
Other Study ID Numbers: LPS14355
2015-000799-92 ( EudraCT Number )
U1111-1172-4772 ( Other Identifier: UTN )
First Submitted: October 22, 2015
First Posted: October 23, 2015
Results First Submitted: April 1, 2018
Results First Posted: May 17, 2018
Last Update Posted: May 17, 2018