ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01476475
Recruitment Status : Completed
First Posted : November 22, 2011
Results First Posted : February 10, 2017
Last Update Posted : February 10, 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 Mellitus
Interventions Drug: Insulin glargine /lixisenatide Fixed Ratio Combination
Drug: Insulin glargine
Drug: Metformin (Background drug)
Enrollment 323
Recruitment Details The study was conducted at 70 centers in 13 countries. A total of 520 participants were screened between November 21, 2011 and June 08, 2012. Out of 520 participants, 197 were screen failure; main reason for screen failure was that glycosylated hemoglobin (HbA1c) values were out of the protocol defined range.
Pre-assignment Details A total of 323 participants were randomized in 1:1 ratio to insulin glargine/lixisenatide fixed ratio combination (FRC) and insulin glargine arms, stratified by screening HbA1c values (<8% or ≥8%) and screening body mass index (BMI) values (<30 kg/m^2, ≥30 kg/m^2).
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description FRC injected subcutaneously once daily (QD) for 24 weeks. Dose individually adjusted. Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Period Title: Overall Study
Started 161 162
Completed 150 159
Not Completed 11 3
Reason Not Completed
Adverse Event             6             0
Poor compliance to protocol             1             1
Other reasons             4             2
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine Total
Hide Arm/Group Description FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted. Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted. Total of all reporting groups
Overall Number of Baseline Participants 161 162 323
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 161 participants 162 participants 323 participants
56.9  (9.5) 56.6  (9.4) 56.7  (9.4)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 161 participants 162 participants 323 participants
Female
81
  50.3%
77
  47.5%
158
  48.9%
Male
80
  49.7%
85
  52.5%
165
  51.1%
Race  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 161 participants 162 participants 323 participants
Caucasian/White 158 160 318
Black 2 1 3
Asian/Oriental 1 1 2
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 161 participants 162 participants 323 participants
Hispanic 35 30 65
Non Hispanic 126 132 258
Screening HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of haemoglobin
Number Analyzed 161 participants 162 participants 323 participants
8.12  (0.80) 8.08  (0.77) 8.10  (0.78)
Baseline BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 161 participants 162 participants 323 participants
32.24  (4.75) 32.02  (4.35) 32.13  (4.55)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 161 participants 162 participants 323 participants
6.29  (4.29) 7.10  (5.27) 6.69  (4.82)
Daily Dose of Metformin  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 161 participants 162 participants 323 participants
2075.8  (440.7) 2093.7  (415.5) 2084.8  (427.7)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 161 participants 162 participants 323 participants
9.76  (2.19) 9.46  (2.16) 9.61  (2.18)
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 24
Hide Description Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP).
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population consisted of all randomized participants received at least 1 dose of IMP and had both baseline and at least 1 post-baseline efficacy assessment. Number of participants analyzed = participants with both baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 160 161
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-1.82  (0.058) -1.64  (0.057)
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 screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline HbA1c value as covariates. A step-down testing procedure described by Hochberg and Tamhane was used to control type-1 error.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority of insulin glargine/lixisenatide FRC versus insulin glargine was tested first, at alpha level of 0.025 (1-sided) and a non-inferiority margin of 0.4% HbA1c. If non-inferiority was established, then a test of superiority of insulin glargine/lixisenatide FRC over insulin glargine would be performed, at alpha level of 0.05 (2-sided). The non-inferiority was assessed using upper bound of 2-sided 95% confidence interval (CI) at ≤0.4%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.312 to -0.037
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments 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 Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline HbA1c value as covariates. If non-inferiority was established, then a test of superiority of insulin glargine/lixisenatide FRC over insulin glargine would be performed, at alpha level of 0.05 (2-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0130
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.312 to -0.037
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
2.Secondary Outcome
Title Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24
Hide Description The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population.Here, number of participants analyzed = participants with both baseline and at least one post-baseline 2-hour PPG assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 151 153
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-7.49  (0.283) -4.33  (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 Analysis was performed using ANCOVA with treatment groups,randomization strata of screening HbA1c(<8.0, ≥8.0%)& screening BMI(<30 kg/m^2, ≥30 kg/m^2),country as fixed effects and baseline 2-hour PPG value as covariates.A step-down testing procedure used to control type-1 error.If non-inferiority demonstrated for primary endpoint,superiority testing on secondary endpoints was performed sequentially in order endpoints are reported(continued only if previous endpoint was statistically significant).
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 -3.17
Confidence Interval (2-Sided) 95%
-3.832 to -2.504
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.337
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
3.Secondary Outcome
Title Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24
Hide Description 2-hour plasma glucose excursion = 2-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with both baseline and at least one post-baseline plasma glucose excursion assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 151 152
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.91  (0.277) -0.67  (0.269)
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 step-down testing procedure (continued only if previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline 2-hour plasma glucose excursion value 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 ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.24
Confidence Interval (2-Sided) 95%
-3.895 to -2.592
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.331
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
4.Secondary Outcome
Title Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24
Hide Description Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, over a single day, once in a week before baseline, before visit Week 12 and before visit Week 24 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 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Baseline, Week 24
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 on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 149 155
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.23  (0.104) -2.93  (0.101)
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 step-down testing procedure (continued only if previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline average 7-point SMPG value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0154
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.550 to -0.058
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.125
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
5.Secondary Outcome
Title Change in Body Weight From Baseline to Week 24
Hide Description Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 3 days after the last injection of IMP.
Time Frame Baseline, Week 24
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 on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 159 160
Least Squares Mean (Standard Error)
Unit of Measure: kg
-0.97  (0.289) 0.48  (0.282)
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 step-down testing procedure (continued only if previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline body weight value 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 ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-2.110 to -0.773
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.340
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
6.Secondary Outcome
Title Average Daily Insulin Glargine Dose at Week 24
Hide Description Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with insulin glargine dose measured during on-treatment period
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 161 162
Least Squares Mean (Standard Error)
Unit of Measure: Units (U)
36.08  (1.415) 39.32  (1.384)
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 step-down testing procedure (continued only if previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0583
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.24
Confidence Interval (2-Sided) 95%
-6.592 to 0.114
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.704
Estimation Comments Insulin glargine/Lixisenatide FRC vs Insulin glargine
7.Secondary Outcome
Title Change in FPG From Baseline to Week 24
Hide Description Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 1 day after the last injection of IMP.
Time Frame Baseline, Week 24
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 FPG assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 159 160
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.35  (0.130) -3.51  (0.128)
8.Secondary Outcome
Title Percentage of Participants Requiring Rescue Therapy During 24-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 exceed 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 24
Show Outcome Measure DataHide 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 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 161 162
Measure Type: Number
Unit of Measure: percentage of participants
0 0.6
9.Secondary Outcome
Title Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24
Hide Description On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 160 161
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c ≤6.5% 71.9 64.6
HbA1c <7.0% 84.4 78.3
10.Secondary Outcome
Title Change in 30-minute and 1-hour PPG From Baseline to Week 24
Hide Description The 30 minute and 1-hour PPG test measured blood glucose 30 minutes and 1-hour after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Baseline, Week 24
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 PPG assessment during on-treatment period. Here, 'n' signifies number of participants with available data for specified category.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 151 153
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
30-minute PPG (n=151, 153) -5.01  (0.194) -3.76  (0.187)
1-hour PPG (n=150, 153) -5.94  (0.246) -4.10  (0.239)
11.Secondary Outcome
Title Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24
Hide Description 30-minute and 1-hour plasma glucose excursion = 30-minute and 1-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.
Time Frame Baseline, Week 24
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 on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 151 152
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
30-minute plasma glucose excursion (n=151, 152) -1.47  (0.156) -0.05  (0.151)
1-hour plasma glucose excursion (n=150, 152) -2.34  (0.233) -0.44  (0.226)
12.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-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). Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one documented symptomatic hypoglycemia before the introduction of rescue medication and up to 1 day after the last injection of IMP. Otherwise, they were counted as missing data. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP.
Time Frame Baseline up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 160 161
Measure Type: Number
Unit of Measure: percentage of participants
67.5 59.0
13.Secondary Outcome
Title Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24
Hide Description Participants without any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (for HbA1c and body weight) was available and showed non-response. Otherwise, they were counted as missing data.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart or with one of the components (for HbA1c and body weight) showing non-response based on the last post-baseline on-treatment value.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 160 161
Measure Type: Number
Unit of Measure: percentage of participants
56.3 37.3
14.Secondary Outcome
Title Percentage of Participants With Documented Symptomatic and Severe 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).Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes were associated with sufficient neuroglycopenia to induce seizure, unconsciousness or coma. All episodes in which neurological impairment was severe enough to prevent self-treatment and which were thought to place participants at risk for injury to themselves or others.
Time Frame First dose of study drug up to 3 days after the last dose administration (maximum of 219 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population that included all randomized participants who received at least 1 dose of study medication regardless of the amount of treatment administered.
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine (Lantus® SoloSTAR®)
Hide Arm/Group Description:
FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted.
Overall Number of Participants Analyzed 161 162
Measure Type: Number
Unit of Measure: percentage of participants
Documented symptomatic hypoglycemia 21.7 22.8
Severe Symptomatic Hypoglycemia 0.0 0.0
Time Frame All Adverse events (AEs) were collected from signature of the informed consent from up to the final visit (Week 24) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported adverse events are treatment-emergent AEs that is AEs that developed/worsened during the ‘on treatment period’ (time from the first injection of open-label IMP up to 3 days after the last injection of IMP, regardless of the introduction of rescue therapy).
 
Arm/Group Title Insulin Glargine/Lixisenatide Fixed Ratio Combination Insulin Glargine
Hide Arm/Group Description FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted (median exposure: 169 days). Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted (median exposure: 169 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   9/161 (5.59%)   6/162 (3.70%) 
Cardiac disorders     
Angina pectoris † 1  1/161 (0.62%)  0/162 (0.00%) 
Angina unstable † 1  1/161 (0.62%)  0/162 (0.00%) 
Bradycardia † 1  1/161 (0.62%)  0/162 (0.00%) 
Atrial fibrillation † 1  0/161 (0.00%)  1/162 (0.62%) 
Infections and infestations     
Cellulitis † 1  1/161 (0.62%)  0/162 (0.00%) 
Urinary tract infection † 1  0/161 (0.00%)  1/162 (0.62%) 
Injury, poisoning and procedural complications     
Radius fracture † 1  1/161 (0.62%)  0/162 (0.00%) 
Investigations     
ECG signs of myocardial ischaemia † 1  0/161 (0.00%)  1/162 (0.62%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion † 1  1/161 (0.62%)  0/162 (0.00%) 
Pain in extremity † 1  1/161 (0.62%)  0/162 (0.00%) 
Osteoarthritis † 1  0/161 (0.00%)  1/162 (0.62%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Ovarian cancer † 1  1/161 (0.62%)  0/162 (0.00%) 
Nervous system disorders     
Diabetic neuropathy † 1  1/161 (0.62%)  0/162 (0.00%) 
Sciatica † 1  1/161 (0.62%)  0/162 (0.00%) 
Presyncope † 1  0/161 (0.00%)  1/162 (0.62%) 
Psychiatric disorders     
Depression † 1  0/161 (0.00%)  1/162 (0.62%) 
Renal and urinary disorders     
Calculus ureteric † 1  1/161 (0.62%)  0/162 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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   26/161 (16.15%)   21/162 (12.96%) 
Gastrointestinal disorders     
Nausea † 1  12/161 (7.45%)  0/162 (0.00%) 
Infections and infestations     
Nasopharyngitis † 1  9/161 (5.59%)  9/162 (5.56%) 
Nervous system disorders     
Headache † 1  8/161 (4.97%)  12/162 (7.41%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
[Not Specified]
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 of Results:
Rosenstock J, Diamant M, Aroda VR, Silvestre L, Souhami E, Zhou T, Perfetti R, Fonseca V; LixiLan PoC Study Group. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial. Diabetes Care. 2016 Sep;39(9):1579-86. doi: 10.2337/dc16-0046. Epub 2016 Jun 9.
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01476475     History of Changes
Other Study ID Numbers: ACT12374
2011-002090-36 ( EudraCT Number )
U1111-1121-7111 ( Other Identifier: UTN )
First Submitted: November 4, 2011
First Posted: November 22, 2011
Results First Submitted: December 16, 2016
Results First Posted: February 10, 2017
Last Update Posted: February 10, 2017