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Trial record 47 of 61 for:    Lixisenatide

GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin (GETGOAL-M)

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ClinicalTrials.gov Identifier: NCT00712673
Recruitment Status : Completed
First Posted : July 10, 2008
Results First Posted : December 15, 2016
Last Update Posted : December 15, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Lixisenatide (AVE0010)
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Enrollment 680
Recruitment Details The study was conducted at 133 centers in 16 countries between June 30, 2008 and March 09, 2011. The overall duration of treatment was at least 76 weeks (24 weeks main double-blind treatment; variable double-blind extension treatment).
Pre-assignment Details A total of 1374 patients were screened of which 694 (50.5%) were screen failures; main reason for screen failure was glycosylated hemoglobin (HbA1c) values being out of the defined protocol range (greater than or equal to 7% and less than or equal to 10%). A total of 680 patients were randomized.
Arm/Group Title Placebo (Morning Injection) Placebo (Evening Injection) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description 2-step initiation morning regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. 2-step initiation evening regimen of volume matching placebo: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
Period Title: Overall Study
Started 85 [1] 85 255 255
Safety Population 85 [2] 85 255 255
Modified Intent-to-Treat(mITT)Population 85 [3] 85 255 255
Subgroup for Standardized Meal Test 85 [4] 0 255 0
Completed 64 64 198 185
Not Completed 21 21 57 70
Reason Not Completed
Adverse Event             3             3             21             26
Lack of Efficacy             2             8             8             6
Poor Compliance to Protocol             3             3             4             16
Lost to Follow-up             1             0             2             0
Withdrawal by Subject             6             7             15             20
Familial and Personal Reasons             5             0             5             2
Investigator's Decision             1             0             0             0
Protocol Violation             0             0             2             0
[1]
Randomized.
[2]
All patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
[3]
All patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment.
[4]
Patients from morning injection arms where standardized meal test was performed.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Total
Hide Arm/Group Description Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo. 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. Total of all reporting groups
Overall Number of Baseline Participants 170 255 255 680
Hide Baseline Analysis Population Description
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 170 participants 255 participants 255 participants 680 participants
55.0  (9.4) 54.5  (9.2) 54.8  (10.4) 54.7  (9.7)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 255 participants 255 participants 680 participants
Female
89
  52.4%
157
  61.6%
141
  55.3%
387
  56.9%
Male
81
  47.6%
98
  38.4%
114
  44.7%
293
  43.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 170 participants 255 participants 255 participants 680 participants
Race: Caucasian/White 155 221 228 604
Race: Black 4 7 6 17
Race: Asian/Oriental 11 22 20 53
Race: Other 0 5 1 6
Ethnicity: Hispanic 49 96 98 243
Ethnicity: Non Hispanic 121 159 157 437
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 170 participants 255 participants 255 participants 680 participants
8.06  (0.90) 8.04  (0.86) 8.09  (0.91) 8.06  (0.89)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  Millimole per liter (mmol/L)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
9.51  (2.28) 9.43  (2.15) 9.31  (2.25) 9.40  (2.22)
2-hour Postprandial Plasma Glucose (PPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
15.51  (3.43) 15.62  (3.97) 15.46  (4.03) 15.53  (3.86)
[1]
Measure Description: Number of patients analyzed = 169, 253 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
90.15  (20.14) 90.09  (21.10) 89.05  (20.74) 89.71  (20.70)
Homeostasis Model Assessment for Beta-cell Function (HOMA-beta)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of normal beta cells function
Number Analyzed 170 participants 255 participants 255 participants 680 participants
41.48  (42.12) 42.82  (32.33) 45.21  (46.09) 43.38  (40.38)
[1]
Measure Description: Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (fasting plasma glucose [mmol/L] minus 3.5). Number of patients analyzed = 168, 251 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Adiponectin   [1] 
Mean (Standard Deviation)
Unit of measure:  Microgram per milliliter (mcg/mL)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
5.61  (3.26) 5.25  (2.90) 5.25  (2.93) 5.34  (3.01)
[1]
Measure Description: Number of patients analyzed = 164, 248 and 248 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Fasting Plasma Insulin (FPI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Picomole per liter (pmol/L)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
75.79  (48.02) 83.68  (63.60) 77.90  (65.46) 79.53  (60.84)
[1]
Measure Description: Number of patients analyzed = 168, 251 and 253 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
2-hour Postprandial Plasma Insulin (PPI)   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
374.28  (266.55) 380.53  (260.96) 378.67  (328.19) 378.30  (289.51)
[1]
Measure Description: Number of patients analyzed = 151, 232 and 240 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Fasting C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  Nanomole per liter (nmol/L)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
0.90  (0.36) 0.97  (0.43) 0.94  (0.43) 0.94  (0.41)
[1]
Measure Description: Number of patients analyzed = 164, 252 and 249 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
2-hour Postprandial C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  nmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
2.46  (1.08) 2.56  (1.11) 2.42  (1.16) 2.48  (1.12)
[1]
Measure Description: Number of patients analyzed = 166, 251 and 249 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Fasting Glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  Nanogram per liter (ng/L)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
87.92  (29.05) 88.89  (32.90) 88.53  (27.30) 88.51  (29.88)
[1]
Measure Description: Number of patients analyzed = 162, 242 and 247 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
2-hour Postprandial Glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
101.30  (33.88) 101.46  (34.54) 100.90  (34.12) 101.21  (34.17)
[1]
Measure Description: Number of patients analyzed = 163, 241 and 248 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Fasting Proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
31.68  (20.10) 34.93  (24.14) 32.35  (18.45) 33.16  (21.16)
[1]
Measure Description: Number of patients analyzed = 142, 223 and 226 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
2-hour Postprandial Proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
83.48  (58.02) 83.71  (54.65) 77.19  (53.44) 81.15  (55.05)
[1]
Measure Description: Number of patients analyzed = 139, 204 and 213 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Glucose Excursion   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 170 participants 255 participants 255 participants 680 participants
5.64  (2.81) 6.09  (3.09) 5.80  (3.13) 5.87  (3.04)
[1]
Measure Description: Number of patients analyzed = 168, 252 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
33.12  (6.45) 33.22  (6.85) 32.47  (5.77) 32.91  (6.36)
[1]
Measure Description: BMI was calculated by dividing body weight by the height squared.
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 170 participants 255 participants 255 participants 680 participants
5.87  (4.72) 6.18  (5.25) 6.21  (5.40) 6.11  (5.17)
Duration of Metformin Treatment  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 170 participants 255 participants 255 participants 680 participants
3.34  (3.45) 3.73  (3.34) 3.68  (3.90) 3.61  (3.59)
Metformin Daily Dose  
Mean (Standard Deviation)
Unit of measure:  Milligram (mg)
Number Analyzed 170 participants 255 participants 255 participants 680 participants
2001.18  (439.70) 1968.82  (446.99) 1942.65  (406.17) 1967.10  (430.22)
1.Primary Outcome
Title Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Hide Description Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in Modified Intent-to-treat (mITT) population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population:all randomized patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment, irrespective of compliance with study protocol/procedures. Last observation carried forward used. Number of patients analyzed=patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 164 244 239
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.38  (0.075) -0.87  (0.065) -0.75  (0.066)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Combined), Lixisenatide (Morning Injection)
Comments To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. Statistical testing:2-sided at significance level=0.05. Analysis of co-variance(ANCOVA)included treatment arms, randomization strata of screening HbA1c(<8.0,>=8.0%),BMI(<30,>=30 kg/m^2),country as fixed effects, baseline HbA1c as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Stepwise testing procedure applied to control type 1 error: lixisenatide (morning) compared with placebo (combined), if found statistically significant, then lixisenatide (evening) compared with placebo (combined).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.657 to -0.312
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.088
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Combined), Lixisenatide (Evening Injection)
Comments To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. Statistical testing:2-sided at significance level=0.05. Analysis of co-variance(ANCOVA)included treatment arms, randomization strata of screening HbA1c(<8.0,>=8.0%),BMI(<30,>=30 kg/m^2),country as fixed effects, baseline HbA1c as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Stepwise testing procedure applied to control type 1 error: lixisenatide (morning) compared with placebo (combined), if found statistically significant, then lixisenatide (evening) compared with placebo (combined).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.540 to -0.193
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.088
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data was imputed using last observation carried forward (LOCF). Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 170 253 255
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.25  (0.166) -1.19  (0.145) -0.81  (0.146)
3.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
Hide Description The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 64 200
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.41  (0.588) -5.92  (0.415)
4.Secondary Outcome
Title Change From Baseline in Body Weight at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 168 248 249
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
-1.64  (0.269) -2.01  (0.234) -2.02  (0.236)
5.Secondary Outcome
Title Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline plasma insulin assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 157 237 229
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-6.23  (3.254) -5.09  (2.812) -1.88  (2.862)
6.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline PPI assessment during on-treatment period
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 54 181
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-25.67  (38.028) -87.24  (24.885)
7.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 48 154
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-3.78  (2.246) -7.78  (1.414)
8.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 43 129
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-6.83  (5.253) -18.88  (3.406)
9.Secondary Outcome
Title Change From Baseline in Fasting C-Peptide at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 63 192
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-0.13  (0.031) -0.10  (0.020)
10.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 62 193
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-0.20  (0.137) -0.46  (0.097)
11.Secondary Outcome
Title Change From Baseline in Fasting Glucagon at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 59 191
Least Squares Mean (Standard Error)
Unit of Measure: ng/L
-13.53  (3.054) -13.27  (2.074)
12.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Glucagon at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 62 191
Least Squares Mean (Standard Error)
Unit of Measure: ng/L
-12.79  (3.551) -27.04  (2.467)
13.Secondary Outcome
Title Change From Baseline in Adiponectin at Week 24
Hide Description Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline adiponectin assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 155 236 227
Least Squares Mean (Standard Error)
Unit of Measure: mcg/mL
0.54  (0.183) 0.55  (0.159) 0.58  (0.160)
14.Secondary Outcome
Title Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24
Hide Description Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HOMA-beta assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 157 235 226
Least Squares Mean (Standard Error)
Unit of Measure: % of normal beta cells function
-4.16  (2.823) 7.96  (2.450) 4.80  (2.486)
15.Secondary Outcome
Title Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period
Hide Description Routine fasting self-monitored plasma glucose (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 baseline to Week 8: fasting SMPG/FPG >270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 170 255 255
Measure Type: Number
Unit of Measure: percentage of participants
10.6 2.7 3.9
16.Secondary Outcome
Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
Hide Description The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 164 244 239
Measure Type: Number
Unit of Measure: percentage of participants
22.0 43.0 40.6
17.Secondary Outcome
Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
Hide Description The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 164 244 239
Measure Type: Number
Unit of Measure: percentage of participants
10.4 23.8 19.2
18.Other Pre-specified Outcome
Title Change From Baseline in Glucose Excursion at Week 24
Hide Description Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal teat. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucose excursion assessment during on-treatment period.
Arm/Group Title Placebo (Morning Injection) Lixisenatide (Morning Injection)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo to lixisenatide.
2-step initiation morning regimen of lixisenatide.
Overall Number of Participants Analyzed 63 198
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.76  (0.483) -4.64  (0.340)
19.Other Pre-specified Outcome
Title Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
Hide Description The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
Arm/Group Title Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection)
Hide Arm/Group Description:
Included all patients who received 2-step initiation, morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Overall Number of Participants Analyzed 168 248 249
Measure Type: Number
Unit of Measure: percentage of participants
11.3 14.9 19.3
20.Other Pre-specified Outcome
Title Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
Hide Description Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
Time Frame First dose of study drug up to 3 days after the last dose administration
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Arm/Group Title Placebo (Morning Injection) Placebo (Evening Injection) Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Lixisenatide (Combined)
Hide Arm/Group Description:
2-step initiation morning regimen of volume matching placebo.
2-step initiation evening regimen of volume matching placebo.
Included all patients who received 2-step initiation, morning and evening regimen of volume matching placebo.
2-step initiation morning regimen of lixisenatide.
2-step initiation evening regimen of lixisenatide.
Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Overall Number of Participants Analyzed 85 85 170 255 255 510
Measure Type: Number
Unit of Measure: participants
Symptomatic Hypoglycemia 0 4 4 18 22 40
Severe Symptomatic Hypoglycemia 0 0 0 0 0 0
Time Frame First dose of study drug up to 3 days after the last dose administration
Adverse Event Reporting Description Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
 
Arm/Group Title Placebo (Morning Injection) Placebo (Evening Injection) Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Lixisenatide (Combined)
Hide Arm/Group Description 2-step initiation morning regimen of volume matching placebo. 2-step initiation evening regimen of volume matching placebo. Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo. 2-step initiation morning regimen of lixisenatide. 2-step initiation evening regimen of lixisenatide. Included all patients who received 2-step initiation morning and evening regimen of lixisenatide.
All-Cause Mortality
Placebo (Morning Injection) Placebo (Evening Injection) Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Lixisenatide (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo (Morning Injection) Placebo (Evening Injection) Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Lixisenatide (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/85 (2.35%)   9/85 (10.59%)   11/170 (6.47%)   21/255 (8.24%)   26/255 (10.20%)   47/510 (9.22%) 
Blood and lymphatic system disorders             
Lymphadenitis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Cardiac disorders             
Acute myocardial infarction * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  1/255 (0.39%)  1/255 (0.39%)  2/510 (0.39%) 
Angina unstable * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  1/255 (0.39%)  1/255 (0.39%)  2/510 (0.39%) 
Atrial fibrillation * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Atrioventricular block first degree * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Cardiac failure congestive * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Cardiomyopathy * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Coronary artery disease * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Ventricular extrasystoles * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Endocrine disorders             
Hypothyroidism * 1  1/85 (1.18%)  0/85 (0.00%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Eye disorders             
Retinal haemorrhage * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Vitreous haemorrhage * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Gastrointestinal disorders             
Abdominal adhesions * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Gastric haemorrhage * 1  1/85 (1.18%)  0/85 (0.00%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Gastritis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Haemorrhoids * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Inguinal hernia * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Inguinal hernia, obstructive * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Rectal polyp * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
General disorders             
Necrobiosis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Hepatobiliary disorders             
Cholecystitis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Cholecystitis acute * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Cholelithiasis * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Infections and infestations             
Anal abscess * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Bacterial sepsis * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Escherichia urinary tract infection * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Influenza * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Pneumonia * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  1/255 (0.39%)  2/255 (0.78%)  3/510 (0.59%) 
Staphylococcal sepsis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Injury, poisoning and procedural complications             
Dislocation of vertebra * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Fall * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Humerus fracture * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Joint injury * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Rib fracture * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Skull fracture * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Spinal cord injury * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Spinal fracture * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Wrist fracture * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Investigations             
Pancreatic enzymes increased * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Metabolism and nutrition disorders             
Obesity * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Musculoskeletal and connective tissue disorders             
Osteoarthritis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  3/255 (1.18%)  4/510 (0.78%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Pancreatic carcinoma * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Prostate cancer * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Rectal cancer * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Renal cell carcinoma * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Signet-ring cell carcinoma * 1  1/85 (1.18%)  0/85 (0.00%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Thyroid neoplasm * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Nervous system disorders             
Carpal tunnel syndrome * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Cerebral infarction * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Dizziness * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Hypertensive encephalopathy * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Lacunar infarction * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Ruptured cerebral aneurysm * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Psychiatric disorders             
Insomnia * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Psychosomatic disease * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Suicide attempt * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Renal and urinary disorders             
Nephrolithiasis * 1  0/85 (0.00%)  1/85 (1.18%)  1/170 (0.59%)  0/255 (0.00%)  0/255 (0.00%)  0/510 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Bronchial obstruction * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Pulmonary oedema * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Skin and subcutaneous tissue disorders             
Angioedema * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Rash maculo-papular * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  0/255 (0.00%)  1/510 (0.20%) 
Surgical and medical procedures             
Cardiac pacemaker insertion * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Coronary artery bypass * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
Vascular disorders             
Hypertensive crisis * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  1/255 (0.39%)  2/255 (0.78%)  3/510 (0.59%) 
Peripheral arterial occlusive disease * 1  0/85 (0.00%)  0/85 (0.00%)  0/170 (0.00%)  0/255 (0.00%)  1/255 (0.39%)  1/510 (0.20%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Morning Injection) Placebo (Evening Injection) Placebo (Combined) Lixisenatide (Morning Injection) Lixisenatide (Evening Injection) Lixisenatide (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   45/85 (52.94%)   50/85 (58.82%)   95/170 (55.88%)   182/255 (71.37%)   169/255 (66.27%)   351/510 (68.82%) 
Gastrointestinal disorders             
Abdominal pain * 1  2/85 (2.35%)  2/85 (2.35%)  4/170 (2.35%)  14/255 (5.49%)  6/255 (2.35%)  20/510 (3.92%) 
Abdominal pain upper * 1  3/85 (3.53%)  6/85 (7.06%)  9/170 (5.29%)  11/255 (4.31%)  10/255 (3.92%)  21/510 (4.12%) 
Diarrhoea * 1  10/85 (11.76%)  10/85 (11.76%)  20/170 (11.76%)  39/255 (15.29%)  36/255 (14.12%)  75/510 (14.71%) 
Dyspepsia * 1  1/85 (1.18%)  0/85 (0.00%)  1/170 (0.59%)  15/255 (5.88%)  13/255 (5.10%)  28/510 (5.49%) 
Nausea * 1  7/85 (8.24%)  9/85 (10.59%)  16/170 (9.41%)  64/255 (25.10%)  63/255 (24.71%)  127/510 (24.90%) 
Vomiting * 1  6/85 (7.06%)  3/85 (3.53%)  9/170 (5.29%)  35/255 (13.73%)  40/255 (15.69%)  75/510 (14.71%) 
General disorders             
Fatigue * 1  3/85 (3.53%)  2/85 (2.35%)  5/170 (2.94%)  14/255 (5.49%)  9/255 (3.53%)  23/510 (4.51%) 
Infections and infestations             
Bronchitis * 1  8/85 (9.41%)  6/85 (7.06%)  14/170 (8.24%)  22/255 (8.63%)  6/255 (2.35%)  28/510 (5.49%) 
Gastroenteritis * 1  4/85 (4.71%)  4/85 (4.71%)  8/170 (4.71%)  14/255 (5.49%)  12/255 (4.71%)  26/510 (5.10%) 
Influenza * 1  5/85 (5.88%)  9/85 (10.59%)  14/170 (8.24%)  30/255 (11.76%)  28/255 (10.98%)  58/510 (11.37%) 
Nasopharyngitis * 1  11/85 (12.94%)  15/85 (17.65%)  26/170 (15.29%)  38/255 (14.90%)  20/255 (7.84%)  58/510 (11.37%) 
Pharyngitis * 1  2/85 (2.35%)  3/85 (3.53%)  5/170 (2.94%)  6/255 (2.35%)  16/255 (6.27%)  22/510 (4.31%) 
Upper respiratory tract infection * 1  6/85 (7.06%)  10/85 (11.76%)  16/170 (9.41%)  22/255 (8.63%)  15/255 (5.88%)  37/510 (7.25%) 
Urinary tract infection * 1  2/85 (2.35%)  5/85 (5.88%)  7/170 (4.12%)  15/255 (5.88%)  10/255 (3.92%)  25/510 (4.90%) 
Metabolism and nutrition disorders             
Hypoglycaemia * 1 [1]  0/85 (0.00%)  5/85 (5.88%)  5/170 (2.94%)  23/255 (9.02%)  28/255 (10.98%)  51/510 (10.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  3/85 (3.53%)  2/85 (2.35%)  5/170 (2.94%)  18/255 (7.06%)  9/255 (3.53%)  27/510 (5.29%) 
Back pain * 1  6/85 (7.06%)  6/85 (7.06%)  12/170 (7.06%)  21/255 (8.24%)  21/255 (8.24%)  42/510 (8.24%) 
Osteoarthritis * 1  1/85 (1.18%)  2/85 (2.35%)  3/170 (1.76%)  14/255 (5.49%)  9/255 (3.53%)  23/510 (4.51%) 
Pain in extremity * 1  2/85 (2.35%)  1/85 (1.18%)  3/170 (1.76%)  18/255 (7.06%)  12/255 (4.71%)  30/510 (5.88%) 
Nervous system disorders             
Dizziness * 1  5/85 (5.88%)  6/85 (7.06%)  11/170 (6.47%)  18/255 (7.06%)  14/255 (5.49%)  32/510 (6.27%) 
Headache * 1  8/85 (9.41%)  20/85 (23.53%)  28/170 (16.47%)  49/255 (19.22%)  42/255 (16.47%)  91/510 (17.84%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1  2/85 (2.35%)  5/85 (5.88%)  7/170 (4.12%)  10/255 (3.92%)  9/255 (3.53%)  19/510 (3.73%) 
Vascular disorders             
Hypertension * 1  3/85 (3.53%)  6/85 (7.06%)  9/170 (5.29%)  17/255 (6.67%)  15/255 (5.88%)  32/510 (6.27%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
[1]
Hypoglycaemia adverse event is based on investigator reported hypoglycaemia.
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: NCT00712673     History of Changes
Other Study ID Numbers: EFC6014
EudraCT 2007-005880-80
First Submitted: July 7, 2008
First Posted: July 10, 2008
Results First Submitted: August 18, 2016
Results First Posted: December 15, 2016
Last Update Posted: December 15, 2016