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)

• 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: Sanofi
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care	Total
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
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.

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis
Description	Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

LDL-C ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
Description	Absolute change = HbA1c value at specified week minus HbA1c value at baseline.
Time Frame	Baseline, Week 12 and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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
Description	Absolute change = FPG value at specified week minus FPG value at baseline.
Time Frame	Baseline, Week 12 and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Usual Care
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)

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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#
• EMail: Contact-US@sanofi.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ray KK, Leiter LA, Müller-Wieland D, Cariou B, Colhoun HM, Henry RR, Tinahones FJ, Bujas-Bobanovic M, Domenger C, Letierce A, Samuel R, Del Prato S. Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial. Diabetes Obes Metab. 2018 Jun;20(6):1479-1489. doi: 10.1111/dom.13257. Epub 2018 Mar 23.

Müller-Wieland D, Leiter LA, Cariou B, Letierce A, Colhoun HM, Del Prato S, Henry RR, Tinahones FJ, Aurand L, Maroni J, Ray KK, Bujas-Bobanovic M. Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk. Cardiovasc Diabetol. 2017 May 25;16(1):70. doi: 10.1186/s12933-017-0552-4.

• 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