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Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM (LixiLan-O)

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ClinicalTrials.gov Identifier: NCT02058147
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 Fixed Ratio Combination
Drug: Insulin glargine (HOE901)
Drug: Lixisenatide (AVE0010)
Drug: Metformin
Enrollment 1170
Recruitment Details The study was conducted at 240 centers in 23 countries. A total of 2457 participants were screened between February 12, 2014 and September 16, 2014. 978 participants were not eligible for run-in mainly due to glycosylated hemoglobin (HbA1c) value at screening visit being out of the protocol defined range.
Pre-assignment Details After 2 weeks screening period, 1479 participants underwent 4-week run-in period. 309 participants were run-in failures. A total of 1170 participants were randomized in 2:2:1 to insulin glargine/lixisenatide, insulin glargine and lixisenatide arms respectively in open-label treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Insulin Glargine Lixisenatide
Hide Arm/Group Description FRC injected subcutaneously once daily (QD) for 30 weeks. Dose individually adjusted. Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted. Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Period Title: Overall Study
Started 469 467 234
Treated 469 467 233
Completed 440 440 205
Not Completed 29 27 29
Reason Not Completed
Randomized but not treated             0             0             1
Adverse Event             12             9             21
Lack of Efficacy             1             0             3
Poor compliance to protocol             8             9             4
Other than specified             8             9             0
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide Total
Hide Arm/Group Description FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted. Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted. Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose). Total of all reporting groups
Overall Number of Baseline Participants 469 467 234 1170
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
58.2  (9.5) 58.3  (9.4) 58.7  (8.7) 58.4  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
Female
247
  52.7%
230
  49.3%
101
  43.2%
578
  49.4%
Male
222
  47.3%
237
  50.7%
133
  56.8%
592
  50.6%
Race  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
Caucasian
417
  88.9%
421
  90.1%
216
  92.3%
1054
  90.1%
Black
33
   7.0%
33
   7.1%
12
   5.1%
78
   6.7%
Asian/Oriental
8
   1.7%
7
   1.5%
3
   1.3%
18
   1.5%
Other
11
   2.3%
6
   1.3%
3
   1.3%
20
   1.7%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
Hispanic
85
  18.1%
87
  18.6%
51
  21.8%
223
  19.1%
Not Hispanic
384
  81.9%
380
  81.4%
183
  78.2%
947
  80.9%
Second Oral Anti-diabetic Drug (OAD) Use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
Yes
274
  58.4%
270
  57.8%
133
  56.8%
677
  57.9%
No
195
  41.6%
197
  42.2%
101
  43.2%
493
  42.1%
Second OAD Use at Screening by Class  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
Sulfonylurea
259
  55.2%
249
  53.3%
123
  52.6%
631
  53.9%
Glinide
3
   0.6%
10
   2.1%
5
   2.1%
18
   1.5%
Sodium-glucose co-transporter-2 inhibitor
2
   0.4%
2
   0.4%
0
   0.0%
4
   0.3%
Dipeptidyl peptidase-4 inhibitor
12
   2.6%
11
   2.4%
5
   2.1%
28
   2.4%
None
193
  41.2%
195
  41.8%
101
  43.2%
489
  41.8%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
31.64  (4.4) 31.66  (4.51) 31.99  (4.39) 31.72  (4.44)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
8.89  (5.51) 8.66  (5.59) 8.89  (6.26) 8.80  (5.69)
Daily Dose of Metformin  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
2246.1  (456.8) 2244.7  (444.7) 2267.3  (427.4) 2249.8  (445.9)
HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
8.08  (0.71) 8.08  (0.69) 8.13  (0.72) 8.09  (0.70)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 469 participants 467 participants 234 participants 1170 participants
9.87  (2.35) 9.75  (2.32) 9.75  (2.19) 9.80  (2.31)
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 30
Hide Description

Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine.

Change in HbA1c was calculated by subtracting baseline value from Week 30 value.

Time Frame Baseline, Week 30
Show Outcome Measure DataHide 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 467 464 233
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-1.63  (0.038) -1.34  (0.039) -0.85  (0.052)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Lixisenatide
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline HbA1c value-by-visit interaction 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 ≤0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-0.898 to -0.665
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.059
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Lixisenatide
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Analysis was performed using MMRM model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline HbA1c value-by-visit interaction as a covariate.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Predefined non-inferiority margin of 0.3%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.384 to -0.194
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.048
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin glargine
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Insulin Glargine
Comments Test of superiority was also performed as a secondary endpoint according to hierarchical testing procedure. Analysis was performed using MMRM model with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline HbA1c value-by-visit interaction, 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 ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.384 to -0.194
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.048
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 Participants without Week 30 value for HbA1c were counted as non-responders.
Time Frame Week 30
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 468 466 233
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c <7.0% 73.7 59.4 33
HbA1c ≤6.5% 55.8 39.5 19.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Lixisenatide
Comments

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

Analysis was performed using Cochran-Mantel-Haenszel method stratified on randomization strata of Week -1 HbA1c (<8.0%, ≥8.0%) and randomization strata of second OAD 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 ≤0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 40.61
Confidence Interval (2-Sided) 95%
33.63 to 47.59
Estimation Comments HbA1c <7.0%: Insulin Glargine/Lixisenatide FRC vs Lixisenatide.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Lixisenatide
Comments

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

Analysis was performed using Cochran-Mantel-Haenszel method stratified on randomization strata of Week -1 HbA1c (<8.0%, ≥8.0%) and randomization strata of second OAD 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 ≤ 0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 36.38
Confidence Interval (2-Sided) 95%
29.81 to 42.95
Estimation Comments HbA1c ≤6.5%: Insulin Glargine/Lixisenatide FRC vs Lixisenatide.
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 second OAD 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 ≤ 0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 14.31
Confidence Interval (2-Sided) 95%
8.37 to 20.25
Estimation Comments HbA1c <7.0%: Insulin Glargine/Lixisenatide FRC vs Insulin glargine.
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 second OAD 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 ≤ 0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.35
Confidence Interval (2-Sided) 95%
10.13 to 22.58
Estimation Comments HbA1c ≤6.5%: Insulin Glargine/Lixisenatide FRC vs Insulin glargine.
3.Secondary Outcome
Title Change in Plasma Glucose Excursion From Baseline to Week 30
Hide Description Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).
Time Frame Baseline, Week 30
Show Outcome Measure DataHide 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.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 428 425 192
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-2.31  (0.154) -0.18  (0.157) -3.23  (0.216)
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 analysis of covariance (ANCOVA) model with treatment groups, randomization strata of Week -1 HbA1c (<8.0,≥8.0%), randomization strata of second OAD use at screening & country as fixed effects & baseline plasma glucose excursion value as a covariate. Hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially per pre-specified order.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤0.05. The hierarchical testing continued only when primary hypotheses (superiority: FRC to lixisenatide; non-inferiority: FRC to insulin glargine for HbA1c) was statistically significant.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.13
Confidence Interval (2-Sided) 95%
-2.498 to -1.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.185
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
Show Outcome Measure DataHide 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 467 465 233
Least Squares Mean (Standard Error)
Unit of Measure: kg
-0.29  (0.182) 1.11  (0.183) -2.3  (0.256)
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline body weight value-by-visit interaction 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 ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-1.891 to -0.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.25
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin glargine
5.Secondary Outcome
Title Change in Fasting Plasma Glucose (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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analysed = 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 465 465 232
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.46  (0.09) -3.27  (0.091) -1.5  (0.124)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Lixisenatide
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline FPG value-by-visit interaction 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 ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.96
Confidence Interval (2-Sided) 95%
-2.246 to -1.682
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.144
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Lixisenatide
6.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
Show Outcome Measure DataHide 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 421 411 204
Least Squares Mean (Standard Deviation)
Unit of Measure: mmol/L
-3.35  (0.081) -2.66  (0.084) -1.95  (0.111)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Glargine/Lixisenatide Fixed Ratio Combination, Lixisenatide
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline 7-point SMPG value-by-visit interaction 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 ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-1.645 to -1.158
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.124
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Lixisenatide
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects and baseline 7-point SMPG value-by-visit interaction, 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 ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-0.892 to -0.495
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.101
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
7.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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants without any 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 468 466 233
Measure Type: Number
Unit of Measure: percentage of participants
43.2 25.1 27.9
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%, ≥8%) and randomization strata of second OAD 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 ≤ 0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 18.08
Confidence Interval (2-Sided) 95%
12.15 to 24.01
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants without any 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 468 466 233
Measure Type: Number
Unit of Measure: percentage of participants
31.8 18.9 26.2
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 second OAD 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 ≤ 0.05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 12.98
Confidence Interval (2-Sided) 95%
7.5 to 18.45
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
9.Secondary Outcome
Title Average Daily Insulin Glargine Dose at Week 30
Hide Description The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.
Time Frame Week 30
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with insulin glargine dose assessment during study period. Data of this endpoint was planned to be analyzed for Insulin Glargine/Lixisenatide FRC and Insulin glargine arms only, not for lixisenatide arm.
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 injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 467 463
Least Squares Mean (Standard Error)
Unit of Measure: Units (U)
39.77  (0.699) 40.46  (0.701)
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 second OAD use at screening, visits, treatment-by-visit interaction, and country as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4857
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-2.632 to 1.252
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.99
Estimation Comments Insulin Glargine/Lixisenatide FRC vs Insulin Glargine
10.Secondary Outcome
Title Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30
Hide Description The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.
Time Frame Baseline, Week 30
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline 2-hour PPG assessment during study period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 430 430 196
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-5.68  (0.176) -3.31  (0.178) -4.58  (0.245)
11.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7.0% at Week 30 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). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.
Time Frame Baseline up to Week 30
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Participants without Week 30 value for HbA1c were counted as non-responders.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 468 466 233
Measure Type: Number
Unit of Measure: percentage of participants
53.6 44.4 30.5
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) was 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 468 466 233
Measure Type: Number
Unit of Measure: percentage of participants
3.6 3.4 12.4
13.Secondary Outcome
Title Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year
Hide Description Documented symptomatic hypoglycemia was an event during which 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)
Show Outcome Measure DataHide 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 Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 469 467 233
Measure Type: Number
Unit of Measure: Events per subject-year
1.44 1.22 0.34
14.Secondary Outcome
Title Percentage of Participants With Documented Symptomatic Hypoglycemia
Hide Description Documented symptomatic hypoglycemia was an event during which 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 469 467 233
Measure Type: Number
Unit of Measure: percentage of participants
25.6 23.6 6.4
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 have 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 of 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description:
FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.
Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Number of Participants Analyzed 469 467 233
Measure Type: Number
Unit of Measure: percentage of participants
0 0.2 0
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) 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-treatment period’ (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
 
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Hide Arm/Group Description FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days). Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days). Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose) median exposure: 211 days).
All-Cause Mortality
Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Lixisenatide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/469 (3.84%)   19/467 (4.07%)   9/233 (3.86%) 
Blood and lymphatic system disorders       
Pancytopenia  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Cardiac disorders       
Cardiac failure congestive  1  1/469 (0.21%)  1/467 (0.21%)  0/233 (0.00%) 
Palpitations  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Acute myocardial infarction  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Cardiac failure acute  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Cardiac failure chronic  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Coronary artery disease  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Myocardial infarction  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Gastrointestinal disorders       
Oesophagitis  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
General disorders       
Death  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Non-cardiac chest pain  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Hepatobiliary disorders       
Cholecystitis chronic  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Infections and infestations       
Urinary tract infection  1  2/469 (0.43%)  0/467 (0.00%)  0/233 (0.00%) 
Erysipelas  1  1/469 (0.21%)  0/467 (0.00%)  1/233 (0.43%) 
Febrile infection  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Bronchitis  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Meningitis staphylococcal  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Pneumonia  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Pyelonephritis acute  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Urosepsis  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Injury, poisoning and procedural complications       
Tendon rupture  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Comminuted fracture  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Toxicity to various agents  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Investigations       
Electrocardiogram ST-T segment abnormal  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Lipase increased  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Metabolic acidosis  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Musculoskeletal and connective tissue disorders       
Costochondritis  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Spinal osteoarthritis  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lung cancer metastatic  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Squamous cell carcinoma of skin  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Lung neoplasm malignant  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Metastases to liver  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Pancreatic carcinoma  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Prostate cancer recurrent  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Squamous cell carcinoma of the oral cavity  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Thyroid adenoma  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Nervous system disorders       
Transient ischaemic attack  1  1/469 (0.21%)  0/467 (0.00%)  1/233 (0.43%) 
Lacunar infarction  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Radiculopathy  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Renal and urinary disorders       
Renal colic  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Acute kidney injury  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Bladder prolapse  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Calculus urinary  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Hydronephrosis  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Reproductive system and breast disorders       
Acquired phimosis  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Cervical dysplasia  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Metrorrhagia  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute pulmonary oedema  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Chronic obstructive pulmonary disease  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Dyspnoea  1  0/469 (0.00%)  1/467 (0.21%)  0/233 (0.00%) 
Respiratory failure  1  0/469 (0.00%)  0/467 (0.00%)  1/233 (0.43%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Urticaria  1  1/469 (0.21%)  0/467 (0.00%)  0/233 (0.00%) 
Vascular disorders       
Hypertension  1  1/469 (0.21%)  1/467 (0.21%)  0/233 (0.00%) 
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 Lixisenatide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   138/469 (29.42%)   85/467 (18.20%)   98/233 (42.06%) 
Gastrointestinal disorders       
Nausea  1  45/469 (9.59%)  17/467 (3.64%)  56/233 (24.03%) 
Diarrhoea  1  42/469 (8.96%)  20/467 (4.28%)  21/233 (9.01%) 
Vomiting  1  15/469 (3.20%)  7/467 (1.50%)  15/233 (6.44%) 
Infections and infestations       
Upper respiratory tract infection  1  33/469 (7.04%)  23/467 (4.93%)  12/233 (5.15%) 
Nasopharyngitis  1  26/469 (5.54%)  25/467 (5.35%)  15/233 (6.44%) 
Nervous system disorders       
Headache  1  24/469 (5.12%)  15/467 (3.21%)  18/233 (7.73%) 
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
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02058147     History of Changes
Other Study ID Numbers: EFC12404
2013-003131-30 ( EudraCT Number )
U1111-1148-4334 ( 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