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Trial record 30 of 61 for:    Lixisenatide

Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes (LixiLan-L)

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ClinicalTrials.gov Identifier: NCT02058160
Recruitment Status : Completed
First Posted : February 7, 2014
Results First Posted : February 10, 2017
Last Update Posted : May 9, 2017
Sponsor:
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 Type 2 Diabetes
Interventions Drug: Insulin glargine/lixisenatide (HOE901/AVE0010)
Drug: Insulin glargine (HOE901)
Drug: Metformin (Background Drug)
Enrollment 736
Recruitment Details The study was conducted at 236 centers in 18 countries. A total of 1930 participants were screened between January 27, 2014 and October 15, 2014. 912 participants were not eligible for run-in-phase mainly due to glycated hemoglobin (HbA1c) value being out of the protocol defined range.
Pre-assignment Details After screening phase, 1018 participants entered 6 week run–in phase during which participants were switched (if necessary) to insulin glargine and dose was titrated/stabilized, any oral anti-diabetic drugs (OAD) other than metformin were stopped. 282 participants were run-in failures and 736 were randomized in 1:1(FRC:insulin glargine arms) ratio.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Insulin Glargine
Hide Arm/Group Description FRC injected subcutaneously once daily (QD) for 30 weeks. Dose individually adjusted. Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Period Title: Overall Study
Started 367 369
Treated 365 365
Completed 336 355
Not Completed 31 14
Reason Not Completed
Randomized but not treated             2             4
Poor compliance to protocol             4             1
Adverse Event             12             3
Lost to Follow-up             1             0
Other than specified above             12             6
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Total
Hide Arm/Group Description FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted. Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted. Total of all reporting groups
Overall Number of Baseline Participants 367 369 736
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 367 participants 369 participants 736 participants
59.6  (9.4) 60.3  (8.7) 60.0  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 367 participants 369 participants 736 participants
Female
202
  55.0%
190
  51.5%
392
  53.3%
Male
165
  45.0%
179
  48.5%
344
  46.7%
Race  
Measure Type: Count of Participants
Unit of measure:  Participants
Caucasian Number Analyzed 367 participants 369 participants 736 participants
337
  91.8%
338
  91.6%
675
  91.7%
Black Number Analyzed 367 participants 369 participants 736 participants
17
   4.6%
21
   5.7%
38
   5.2%
Asian/Oriental Number Analyzed 367 participants 369 participants 736 participants
12
   3.3%
8
   2.2%
20
   2.7%
Other Number Analyzed 367 participants 369 participants 736 participants
1
   0.3%
2
   0.5%
3
   0.4%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic Number Analyzed 367 participants 369 participants 736 participants
66
  18.0%
66
  17.9%
132
  17.9%
Not Hispanic Number Analyzed 367 participants 369 participants 736 participants
301
  82.0%
303
  82.1%
604
  82.1%
OAD Use  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 367 participants 369 participants 736 participants
349
  95.1%
350
  94.9%
699
  95.0%
No Number Analyzed 367 participants 369 participants 736 participants
18
   4.9%
19
   5.1%
37
   5.0%
OAD Use at Screening by Class  
Measure Type: Count of Participants
Unit of measure:  Participants
Metformin Number Analyzed 367 participants 369 participants 736 participants
170
  46.3%
190
  51.5%
360
  48.9%
Sulfonylurea Number Analyzed 367 participants 369 participants 736 participants
16
   4.4%
14
   3.8%
30
   4.1%
Sodium glucose co-transporter 2 (SGLT-2) inhibitor Number Analyzed 367 participants 369 participants 736 participants
0
   0.0%
1
   0.3%
1
   0.1%
Dipeptidyl-peptidase 4 (DPP-4) inhibitor Number Analyzed 367 participants 369 participants 736 participants
2
   0.5%
4
   1.1%
6
   0.8%
Glinide Number Analyzed 367 participants 369 participants 736 participants
1
   0.3%
1
   0.3%
2
   0.3%
Metformin + Sulfonylurea Number Analyzed 367 participants 369 participants 736 participants
137
  37.3%
118
  32.0%
255
  34.6%
Metformin + DPP-4 inhibitor Number Analyzed 367 participants 369 participants 736 participants
20
   5.4%
18
   4.9%
38
   5.2%
Metfomrin + Glinide Number Analyzed 367 participants 369 participants 736 participants
2
   0.5%
3
   0.8%
5
   0.7%
Sulfonylurea + DPP-4 inhibitor Number Analyzed 367 participants 369 participants 736 participants
1
   0.3%
1
   0.3%
2
   0.3%
None Number Analyzed 367 participants 369 participants 736 participants
18
   4.9%
19
   5.1%
37
   5.0%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 367 participants 369 participants 736 participants
31.33  (4.25) 30.96  (4.15) 31.14  (4.20)
Duration of Diabetes   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 367 participants 368 participants 735 participants
12.02  (6.64) 12.13  (6.85) 12.08  (6.74)
[1]
Measure Analysis Population Description: Only participants with available data for this baseline measure were included in the analysis.
Daily Dose of Metformin   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 329 participants 329 participants 658 participants
2082.8  (499.2) 2042.0  (455.9) 2062.4  (478.1)
[1]
Measure Analysis Population Description: Only participants with available data for this baseline measure were included in the analysis.
Screening Glycated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 367 participants 369 participants 736 participants
8.51  (0.65) 8.54  (0.67) 8.53  (0.66)
Baseline HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 367 participants 369 participants 736 participants
8.07  (0.68) 8.08  (0.73) 8.08  (0.71)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 367 participants 369 participants 736 participants
7.34  (1.95) 7.36  (2.12) 7.35  (2.04)
1.Primary Outcome
Title Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30
Hide Description Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population: all randomized participants who had both baseline and at least one post-baseline efficacy assessment. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 364 364
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-1.13  (0.057) -0.62  (0.055)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Analysis was performed using Mixed-effect model with repeated measures (MMRM) with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening, visits, treatment-by-visit interaction and country as fixed effects and baseline HbA1c value-by-visit interaction as covariates. A hierarchical testing procedure was used to control type I error and handle multiple endpoint analyses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.633 to -0.397
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
2.Secondary Outcome
Title Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30
Hide Description [Not Specified]
Time Frame Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants with no value for HbA1c at Week 30 were counted as non-responders.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 366 365
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c <7.0% 54.9 29.6
HbA1c ≤ 6.5% 33.9 14.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments

HbA1c <7.0%: Insulin Glargine/Lixisenatide FRC vs Insulin Glargine.

Analysis was performed using Cochran-Mantel-Haenszel method stratified on randomization strata of Week -1 HbA1c (<8.0%, ≥8.0%) and randomization strata of metformin use at screening. This analysis was out of testing order.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.52
Confidence Interval (2-Sided) 95%
18.94 to 32.10
Estimation Comments HbA1c <7.0%: Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments

HbA1c ≤6.5%: Insulin Glargine/Lixisenatide FRC vs Insulin Glargine.

Analysis was performed using Cochran-Mantel-Haenszel method stratified on randomization strata of Week -1 HbA1c (<8.0%, ≥8.0%) and randomization strata of metformin use at screening. This analysis was out of testing order.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 19.76
Confidence Interval (2-Sided) 95%
13.90 to 25.62
Estimation Comments HbA1c ≤6.5%: Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
3.Secondary Outcome
Title Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30
Hide Description Plasma glucose excursion = 2-hour postprandial glucose (PPG) minus plasma glucose value obtained 30 minutes prior to the start of the meal and before investigational medicinal product (IMP) administration, if IMP was injected before breakfast. Change in plasma glucose excursions was calculated by subtracting baseline value from Week 30 value.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline plasma glucose excursion assessment during study period. Missing data was imputed using last observation carried forward (LOCF).
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 329 336
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.9  (0.285) -0.47  (0.274)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Testing according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). Analysis was performed using analysis of covariance (ANCOVA) model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening and country as fixed effects and baseline 2-hour plasma glucose excursion value as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.43
Confidence Interval (2-Sided) 95%
-3.925 to -2.939
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.251
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
4.Secondary Outcome
Title Change in Body Weight From Baseline to Week 30
Hide Description Change in body weight was calculated by subtracting baseline value from Week 30 value.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 365 365
Least Squares Mean (Standard Error)
Unit of Measure: kg
-0.67  (0.181) 0.7  (0.178)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Testing according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). Analysis was performed using MMRM model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening, scheduled visits, treatment-by-visit interaction and country as fixed effects and baseline body weight value-by-visit interaction as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.37
Confidence Interval (2-Sided) 95%
-1.808 to -0.93
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.224
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
5.Secondary Outcome
Title Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30
Hide Description Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7 time points was calculated. Change in average 7 point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed= participants with baseline and at least one post-baseline 7-point SMPG assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 323 320
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.5  (0.137) -0.6  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Testing according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). Analysis was performed using MMRM model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening, scheduled visits, treatment-by-visit interaction and country as fixed effects and baseline average SMPG value-by-visit interaction as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.154 to -0.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.131
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
6.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30
Hide Description [Not Specified]
Time Frame Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants without HbA1c and/or body weight value at Week 30 were counted as non-responders.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 366 365
Measure Type: Number
Unit of Measure: percentage of participants
34.2 13.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Testing according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified on randomization strata of Week -1 HbA1c (<8.0%, ≥8.0%) and randomization strata of metformin use at screening.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentage
Estimated Value 20.82
Confidence Interval (2-Sided) 95%
14.98 to 26.66
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
7.Secondary Outcome
Title Change in Daily Insulin Glargine Dose From Baseline to Week 30
Hide Description [Not Specified]
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. The analysis included scheduled measurements obtained up to the date of last injection of IMP. Here, number of participants analyzed= participants with insulin glargine dose assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 364 365
Least Squares Mean (Standard Error)
Unit of Measure: Units (U)
10.64  (0.601) 10.89  (0.587)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Testing according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). Analysis was performed using MMRM model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening, scheduled visits, treatment-by-visit interaction and country as fixed effects and baseline daily insulin glargine dose-by-visit interaction as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7362
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.762 to 1.246
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.766
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
8.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Hide Description Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Time Frame Baseline up to Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants without HbA1c and/or body weight value at Week 30 were counted as non-responders.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 366 365
Measure Type: Number
Unit of Measure: percentage of participants
19.9 9.0
9.Secondary Outcome
Title Change in FPG From Baseline to Week 30
Hide Description Change in FPG was calculated by subtracting baseline value from Week 30 value.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed= participants with baseline and at least one post-baseline FPG assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 364 364
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.35  (0.142) -0.46  (0.138)
10.Secondary Outcome
Title Change in 2-hour PPG From Baseline to Week 30
Hide Description Change in PPG was calculated by subtracting baseline value from Week 30 value.
Time Frame Baseline, Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed= participants with baseline and at least one post-baseline PPG assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 332 340
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-4.72  (0.322) -1.39  (0.31)
11.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7.0% With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Hide Description Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Time Frame Baseline up to Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants with no value for HbA1c at Week 30 were counted as non-responders.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 366 365
Measure Type: Number
Unit of Measure: percentage of participants
31.7 18.6
12.Secondary Outcome
Title Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period
Hide Description Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8%.
Time Frame Baseline up to Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 366 365
Measure Type: Number
Unit of Measure: percentage of participants
2.7 6
13.Secondary Outcome
Title Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year
Hide Description Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Time Frame First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population defined as all randomized participants who received at least one dose of IMP regardless of the amount of treatment administered.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 365 365
Measure Type: Number
Unit of Measure: events per subject-year
3.03 4.22
14.Secondary Outcome
Title Percentage of Participants With Documented Symptomatic Hypoglycemia
Hide Description Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Time Frame First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 365 365
Measure Type: Number
Unit of Measure: percentage of participants
40 42.5
15.Secondary Outcome
Title Percentage of Participants With Severe Symptomatic Hypoglycemia
Hide Description Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not had been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk for injury to themselves or others.
Time Frame First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 365 365
Measure Type: Number
Unit of Measure: percentage of participants
1.1 0.3
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs are treatment-emergent that is AEs that developed/worsened during ‘on-emergent period’ (time from first injection of open-label IMP up to 3 days after the last injection of IMP). Analysis was performed on safety population.
 
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days). Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 210 days).
All-Cause Mortality
Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   20/365 (5.48%)   18/365 (4.93%) 
Cardiac disorders     
Acute myocardial infarction  1  2/365 (0.55%)  0/365 (0.00%) 
Angina unstable  1  2/365 (0.55%)  0/365 (0.00%) 
Arteriosclerosis coronary artery  1  1/365 (0.27%)  0/365 (0.00%) 
Myocardial infarction  1  1/365 (0.27%)  0/365 (0.00%) 
Supraventricular tachycardia  1  1/365 (0.27%)  0/365 (0.00%) 
Cardiac failure congestive  1  0/365 (0.00%)  1/365 (0.27%) 
Cardiopulmonary failure  1  0/365 (0.00%)  1/365 (0.27%) 
Eye disorders     
Glaucoma  1  0/365 (0.00%)  1/365 (0.27%) 
General disorders     
Chest discomfort  1  0/365 (0.00%)  1/365 (0.27%) 
Non-cardiac chest pain  1  0/365 (0.00%)  2/365 (0.55%) 
Hepatobiliary disorders     
Cholecystitis chronic  1  1/365 (0.27%)  0/365 (0.00%) 
Cholecystitis acute  1  0/365 (0.00%)  1/365 (0.27%) 
Infections and infestations     
Pneumonia  1  1/365 (0.27%)  1/365 (0.27%) 
Osteomyelitis  1  0/365 (0.00%)  1/365 (0.27%) 
Wound infection  1  0/365 (0.00%)  1/365 (0.27%) 
Injury, poisoning and procedural complications     
Scar  1  1/365 (0.27%)  0/365 (0.00%) 
Subdural haematoma  1  1/365 (0.27%)  0/365 (0.00%) 
Meniscus injury  1  0/365 (0.00%)  1/365 (0.27%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  2/365 (0.55%)  1/365 (0.27%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  1/365 (0.27%)  0/365 (0.00%) 
Tendonitis  1  1/365 (0.27%)  0/365 (0.00%) 
Intervertebral disc protrusion  1  0/365 (0.00%)  1/365 (0.27%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  1  1/365 (0.27%)  0/365 (0.00%) 
Benign gastric neoplasm  1  1/365 (0.27%)  0/365 (0.00%) 
Breast cancer  1  1/365 (0.27%)  0/365 (0.00%) 
Squamous cell carcinoma of the tongue  1  1/365 (0.27%)  0/365 (0.00%) 
Gallbladder cancer  1  0/365 (0.00%)  1/365 (0.27%) 
Kaposi's sarcoma  1  0/365 (0.00%)  1/365 (0.27%) 
Nervous system disorders     
Hypoglycaemic unconsciousness  1  2/365 (0.55%)  0/365 (0.00%) 
Hypoglycaemic seizure  1  1/365 (0.27%)  0/365 (0.00%) 
Renal and urinary disorders     
Renal impairment  1  0/365 (0.00%)  1/365 (0.27%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/365 (0.00%)  1/365 (0.27%) 
Vascular disorders     
Hypertension  1  0/365 (0.00%)  1/365 (0.27%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   81/365 (22.19%)   42/365 (11.51%) 
Gastrointestinal disorders     
Nausea  1  38/365 (10.41%)  2/365 (0.55%) 
Infections and infestations     
Nasopharyngitis  1  32/365 (8.77%)  32/365 (8.77%) 
Nervous system disorders     
Headache  1  21/365 (5.75%)  10/365 (2.74%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02058160     History of Changes
Other Study ID Numbers: EFC12405
2013-003132-79 ( EudraCT Number )
U1111-1148-4351 ( Other Identifier: UTN )
First Submitted: February 6, 2014
First Posted: February 7, 2014
Results First Submitted: December 16, 2016
Results First Posted: February 10, 2017
Last Update Posted: May 9, 2017