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Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)

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ClinicalTrials.gov Identifier: NCT02642159
Recruitment Status : Completed
First Posted : December 30, 2015
Results First Posted : May 1, 2018
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Dyslipidemia
Interventions Drug: Alirocumab
Drug: Statins
Drug: Ezetimibe
Drug: Fenofibrate
Drug: Nicotinic acid
Drug: Omega-3 fatty acids
Drug: Antihyperglycemic Drug
Enrollment 413
Recruitment Details The study was conducted at 119 centers in 15 countries. A total of 864 participants were screened between March 2016 and September 2016, 451 of whom were screen failures. Screen failures were mainly due to inclusion criteria not met.
Pre-assignment Details Randomization was stratified by investigator's choice of usual care therapy, which was pre-specified prior to randomization. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 2:1 ratio (alirocumab: usual care) after confirmation of selection criteria. 413 participants were randomized.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Hide Arm/Group Description Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapies (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels >=100 mg/dL (2.59 mmol/L) at Week 8. Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Period Title: Overall Study
Started 276 [1] 137 [1]
Treated (Safety Population) 275 137
ITT Population 273 136
ITT: Intent to Prescribe Fenofibrate 47 [2] 24
Completed [3] 245 129
Not Completed 31 8
Reason Not Completed
Randomized but not treated             1             0
Adverse Event             10             4
Withdrawal by Subject             9             1
Poor compliance to study protocol             1             0
Other than specified above             10             3
[1]
Randomized
[2]
Fenofibrate was only ‘intended to prescribe’ in the Alirocumab arm but not actually administered.
[3]
Completed = treatment completion
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care Total
Hide Arm/Group Description Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8. Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 276 137 413
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 276 participants 137 participants 413 participants
62.8  (9.3) 64.1  (8.8) 63.2  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 276 participants 137 participants 413 participants
Female
129
  46.7%
68
  49.6%
197
  47.7%
Male
147
  53.3%
69
  50.4%
216
  52.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 276 participants 137 participants 413 participants
Hispanic or Latino
35
  12.7%
14
  10.2%
49
  11.9%
Not Hispanic or Latino
240
  87.0%
123
  89.8%
363
  87.9%
Unknown or Not Reported
1
   0.4%
0
   0.0%
1
   0.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 276 participants 137 participants 413 participants
White/Caucasian
247
  89.5%
123
  89.8%
370
  89.6%
Black
16
   5.8%
6
   4.4%
22
   5.3%
Asian/Oriental
3
   1.1%
7
   5.1%
10
   2.4%
American Indian or Alaska Native
4
   1.4%
0
   0.0%
4
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
6
   2.2%
1
   0.7%
7
   1.7%
Non-HDL-C   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 276 participants 137 participants 413 participants
155.1  (46.2) 161.5  (48.8) 157.2  (47.1)
[1]
Measure Description: non-HDL-C = Total cholesterol (Total-C) minus high-density lipoprotein cholesterol (HDL-C)
Non-HDL-C   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 276 participants 137 participants 413 participants
4.0  (1.2) 4.2  (1.2) 4.073  (1.221)
[1]
Measure Description: non-HDL-C = Total-C minus HDL-C
Intent to Prescribe Treatment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 276 participants 137 participants 413 participants
Fenofibrate
48
  17.4%
24
  17.5%
72
  17.4%
No additional LMT
79
  28.6%
39
  28.5%
118
  28.6%
Ezetimibe
104
  37.7%
52
  38.0%
156
  37.8%
Omega-3 fatty acids
43
  15.6%
21
  15.3%
64
  15.5%
Nicotinic acid
2
   0.7%
1
   0.7%
3
   0.7%
[1]
Measure Description: Randomization was stratified by the Investigator’s selection of usual care therapy prior to randomization. LMTs were only ‘intended to prescribe’ in the Alirocumab arm but not actually administered.
1.Primary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 24: Overall 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 8 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 non-HDL-C value on- or off-treatment.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-37.3  (3.0) -4.7  (3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Alirocumab group was compared to usual care 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 <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -32.5
Confidence Interval (2-Sided) 97.5%
-38.1 to -27.0
Estimation Comments Alirocumab vs. usual care
2.Primary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-41.7  (3.4) -8.5  (4.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Alirocumab group was compared to usual care group for the intent to prescribe fenofibrate 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 <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -33.3
Confidence Interval (2-Sided) 97.5%
-46.6 to -19.9
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
3.Secondary Outcome
Title Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall 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 8 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 value on-or off-treatment (LDL-C ITT population).
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-43.3  (3.6) -0.3  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses for overall ITT analysis. 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 0.025 level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -43.0
Confidence Interval (2-Sided) 97.5%
-49.7 to -36.3
Estimation Comments Alirocumab vs. usual care
4.Secondary Outcome
Title Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
LDL-C ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-47.0  (4.2) 8.7  (5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments A separate hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses for ITT-intent to prescribe fenofibrate stratum. 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 0.025 level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -55.7
Confidence Interval (2-Sided) 97.5%
-71.8 to -39.6
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
5.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-35.5  (2.9) -9.4  (3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -26.1
Confidence Interval (2-Sided) 97.5%
-31.5 to -20.7
Estimation Comments Alirocumab vs. usual care
6.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-34.7  (3.2) -7.3  (4.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT-intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -27.4
Confidence Interval (2-Sided) 97.5%
-40.0 to -14.8
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
7.Secondary Outcome
Title Percent Change From Baseline in Measured LDL-C at Week 12: Overall 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 8 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
LDL-C ITT population.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-41.7  (3.3) -7.0  (3.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -34.7
Confidence Interval (2-Sided) 97.5%
-40.8 to -28.6
Estimation Comments Alirocumab vs. usual care
8.Secondary Outcome
Title Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum
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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
LDL-C ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-44.3  (3.6) 5.4  (5.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT-intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -49.7
Confidence Interval (2-Sided) 97.5%
-63.7 to -35.8
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
9.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-33.8  (2.7) -1.6  (3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -32.3
Confidence Interval (2-Sided) 97.5%
-37.3 to -27.2
Estimation Comments Alirocumab vs. usual care
10.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo-B ITT population.Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-38.9  (3.1) -3.8  (4.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT- intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.2
Confidence Interval (2-Sided) 97.5%
-47.4 to -22.9
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
11.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-27.4  (2.3) -2.8  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.6
Confidence Interval (2-Sided) 97.5%
-28.8 to -20.3
Estimation Comments Alirocumab vs. usual care
12.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-30.9  (2.6) -5.7  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT- intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.3
Confidence Interval (2-Sided) 97.5%
-35.4 to -15.1
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
13.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis
Hide Description Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Mean (Standard Error)
Unit of Measure: Percent change
-23.7  (1.9) 3.7  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance <=0.025.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -27.4
Confidence Interval (2-Sided) 97.5%
-34.6 to -20.1
Estimation Comments Alirocumab vs. usual care
14.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Mean (Standard Error)
Unit of Measure: Percent change
-18.9  (4.4) 3.9  (6.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT- intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0040
Comments Threshold for significance <=0.025.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -22.8
Confidence Interval (2-Sided) 97.5%
-40.6 to -5.0
Estimation Comments Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
15.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis
Hide Description Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Mean (Standard Error)
Unit of Measure: Percent change
-13.0  (2.0) -8.8  (2.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of overall ITT analysis was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2191
Comments Threshold for significance <=0.025.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -4.2
Confidence Interval (2-Sided) 97.5%
-11.8 to 3.4
Estimation Comments Alirocumab vs. usual care
16.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Mean (Standard Error)
Unit of Measure: Percent change
-15.4  (4.7) -24.4  (6.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alirocumab 75 mg Q2W/Up to 150 mg Q2W, Usual Care: Intent to Prescribe Fenofibrate
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint of ITT- intent to prescribe fenofibrate stratum was statistically significant).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2651
Comments Threshold for significance <=0.025.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value 9.0
Confidence Interval (2-Sided) 97.5%
-9.1 to 27.1
Estimation Comments [Not Specified]
Other Statistical Analysis Alirocumab (intent to prescribe fenofibrate) vs. usual care (intent to prescribe fenofibrate)
17.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24 : Overall ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
14.5  (2.5) 8.2  (2.7)
18.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 47 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
13.5  (2.9) 12.3  (4.1)
19.Secondary Outcome
Title Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall 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 8 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 on- or off-treatment (LDL-C particle number ITT population).
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 270 135
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-41.6  (3.0) -3.9  (3.4)
20.Secondary Outcome
Title Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
Hide Description LDL-C particle number was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
LDL-C particle number ITT population. Here, ‘Number of participants analyzed’ = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.
Arm/Group Title Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care: Intent to Prescribe Fenofibrate
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy with fenofibrate as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 46 24
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-45.4  (3.5) -2.9  (5.0)
21.Secondary Outcome
Title Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis
Hide Description Absolute change = HbA1c value at specified week minus HbA1c value at baseline.
Time Frame Baseline, Week 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Mean (Standard Deviation)
Unit of Measure: mmol/mol
Change at Week 12 Number Analyzed 265 participants 133 participants
0.59  (6.82) 0.43  (5.70)
Change at Week 24 Number Analyzed 251 participants 128 participants
2.84  (8.04) 2.40  (8.19)
22.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis
Hide Description Absolute change = FPG value at specified week minus FPG value at baseline.
Time Frame Baseline, Week 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Mean (Standard Deviation)
Unit of Measure: mmol/L
Change at Week 12 Number Analyzed 262 participants 133 participants
0.45  (2.43) 0.21  (1.86)
Change at Week 24 Number Analyzed 251 participants 128 participants
0.68  (2.54) 0.03  (2.54)
23.Secondary Outcome
Title Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall 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 week minus baseline value.
Time Frame Baseline, Week 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 Usual Care
Hide Arm/Group Description:
Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8.
Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Number of Participants Analyzed 273 136
Mean (Standard Deviation)
Unit of Measure: Glucose lowering treatments
Change at Week 12 Number Analyzed 271 participants 136 participants
0.04  (0.30) 0.04  (0.19)
Change at Week 24 Number Analyzed 267 participants 135 participants
0.07  (0.37) 0.04  (0.23)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs and deaths are TEAEs that are 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 Usual Care
Hide Arm/Group Description Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels >=100 mg/dL (2.59 mmol/L) at Week 8. Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator’s judgment for 24 weeks.
All-Cause Mortality
Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Affected / at Risk (%) Affected / at Risk (%)
Total   1/275 (0.36%)   0/137 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Alirocumab 75 mg Q2W/Up to 150 mg Q2W Usual Care
Affected / at Risk (%) Affected / at Risk (%)
Total   26/275 (9.45%)   12/137 (8.76%) 
Cardiac disorders     
Acute myocardial infarction  1  1/275 (0.36%)  1/137 (0.73%) 
Angina unstable  1  3/275 (1.09%)  0/137 (0.00%) 
Coronary artery disease  1  1/275 (0.36%)  0/137 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  1/275 (0.36%)  0/137 (0.00%) 
Eye disorders     
Glaucoma  1  1/275 (0.36%)  0/137 (0.00%) 
Gastrointestinal disorders     
Gastrooesophageal reflux disease  1  1/275 (0.36%)  0/137 (0.00%) 
Rectal haemorrhage  1  1/275 (0.36%)  0/137 (0.00%) 
Small intestinal obstruction  1  1/275 (0.36%)  0/137 (0.00%) 
General disorders     
Death  1  1/275 (0.36%)  0/137 (0.00%) 
Non-cardiac chest pain  1  2/275 (0.73%)  0/137 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/275 (0.00%)  1/137 (0.73%) 
Infections and infestations     
Appendicitis  1  1/275 (0.36%)  0/137 (0.00%) 
Diabetic foot infection  1  1/275 (0.36%)  0/137 (0.00%) 
Osteomyelitis  1  1/275 (0.36%)  0/137 (0.00%) 
Pneumonia  1  2/275 (0.73%)  0/137 (0.00%) 
Urinary tract infection  1  1/275 (0.36%)  0/137 (0.00%) 
Injury, poisoning and procedural complications     
Lower limb fracture  1  1/275 (0.36%)  0/137 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/275 (0.00%)  1/137 (0.73%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/275 (0.00%)  1/137 (0.73%) 
Spinal osteoarthritis  1  0/275 (0.00%)  1/137 (0.73%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder neoplasm  1  1/275 (0.36%)  0/137 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  0/275 (0.00%)  1/137 (0.73%) 
Dizziness  1  0/275 (0.00%)  1/137 (0.73%) 
Facial paralysis  1  0/275 (0.00%)  1/137 (0.73%) 
Ischaemic stroke  1  2/275 (0.73%)  2/137 (1.46%) 
Seizure  1  1/275 (0.36%)  0/137 (0.00%) 
Transient ischaemic attack  1  0/275 (0.00%)  1/137 (0.73%) 
Psychiatric disorders     
Bipolar I disorder  1  1/275 (0.36%)  0/137 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/275 (0.36%)  0/137 (0.00%) 
Nephrolithiasis  1  1/275 (0.36%)  0/137 (0.00%) 
Reproductive system and breast disorders     
Vaginal prolapse  1  0/275 (0.00%)  1/137 (0.73%) 
1
Term from vocabulary, MedDra 20.0
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 Usual Care
Affected / at Risk (%) Affected / at Risk (%)
Total   37/275 (13.45%)   27/137 (19.71%) 
Gastrointestinal disorders     
Diarrhoea  1  14/275 (5.09%)  9/137 (6.57%) 
Infections and infestations     
Bronchitis  1  5/275 (1.82%)  7/137 (5.11%) 
Urinary tract infection  1  15/275 (5.45%)  5/137 (3.65%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/275 (2.18%)  8/137 (5.84%) 
1
Term from vocabulary, MedDra 20.0
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
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02642159     History of Changes
Other Study ID Numbers: LPS14354
2015-001934-19 ( EudraCT Number )
U1111-1172-5262 ( Other Identifier: UTN )
First Submitted: December 24, 2015
First Posted: December 30, 2015
Results First Submitted: March 20, 2018
Results First Posted: May 1, 2018
Last Update Posted: May 1, 2018