Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 39 of 61 for:    Lixisenatide

GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Sulfonylurea (GETGOAL-S)

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: NCT00713830
Recruitment Status : Completed
First Posted : July 14, 2008
Results First Posted : December 14, 2016
Last Update Posted : December 14, 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: Sulfonylurea
Drug: Metformin
Enrollment 859
Recruitment Details The study was conducted at 136 centers in 16 countries between July 08, 2008 and January 14, 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 1438 participants were screened of which 579 (40.3%) 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 859 participants were randomized.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description 2-step initiation 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 the end of treatment. 2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
Period Title: Overall Study
Started 286 [1] 573
Modified Intent-to-Treat(mITT)Population 286 [2] 570
Safety Population 285 [3] 574 [4]
Subgroup for Standardized Meal Test 155 [5] 313
Completed 204 396
Not Completed 82 177
Reason Not Completed
Adverse Event             23             71
Lack of Efficacy             24             16
Lost to Follow-up             2             9
Withdrawal by Subject             13             23
Poor Compliance to Protocol             7             14
Familial and Personal Reasons             9             34
Sponsor Decision             4             10
[1]
Randomized.
[2]
All patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment.
[3]
All patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
[4]
1 patient randomized to placebo received Lixisenatide (at least one dose)
[5]
Patients at selected sites where standardized meal challenge test was performed.
Arm/Group Title Placebo Lixisenatide Total
Hide Arm/Group Description 2-step initiation 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 the end of treatment. 2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Total of all reporting groups
Overall Number of Baseline Participants 285 574 859
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.The one patient in the placebo group who received Lixisenatide was described in the Lixisenatide group.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 285 participants 574 participants 859 participants
57.8  (10.1) 57.0  (9.8) 57.2  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 574 participants 859 participants
Female
135
  47.4%
290
  50.5%
425
  49.5%
Male
150
  52.6%
284
  49.5%
434
  50.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 285 participants 574 participants 859 participants
Race: Caucasian/White 151 297 448
Race: Black 9 17 26
Race: Asian/Oriental 125 260 385
Ethnicity: Hispanic 5 18 23
Ethnicity: Non Hispanic 280 556 836
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 285 participants 574 participants 859 participants
8.21  (0.84) 8.28  (0.86) 8.25  (0.85)
2-Hour Postprandial Plasma Glucose (PPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  Millimole per liter (mmol/L)
Number Analyzed 285 participants 574 participants 859 participants
16.44  (3.74) 16.69  (4.02) 16.60  (3.92)
[1]
Measure Description: The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Number of patients analyzed = 154 and 309 for Placebo and Lixisenatide treatment arms, respectively.
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 285 participants 574 participants 859 participants
9.29  (2.37) 9.67  (2.24) 9.55  (2.29)
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 285 participants 574 participants 859 participants
84.42  (22.83) 82.30  (21.76) 83.00  (22.13)
Homeostasis Model Assessment for Beta-cell Function (HOMA-beta)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of normal beta cells function
Number Analyzed 285 participants 574 participants 859 participants
36.43  (39.43) 34.28  (69.82) 34.99  (61.39)
[1]
Measure Description: Beta cell function was assessed by HOMA-beta. HOMA-beta (percentage [%] of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (FPG [mmol/L] minus 3.5). Number of patients analyzed = 152 and 306 for Placebo and Lixisenatide treatment arms, respectively.
Fasting glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  Nanogram per liter (ng/L)
Number Analyzed 285 participants 574 participants 859 participants
0.89  (0.55) 0.83  (0.43) 0.85  (0.47)
[1]
Measure Description: Number of patients analyzed = 152 and 309 for Placebo and Lixisenatide treatment arm, respectively.
2-hour postprandial glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/L
Number Analyzed 285 participants 574 participants 859 participants
102.27  (39.37) 97.83  (31.94) 99.31  (34.60)
[1]
Measure Description: Number of patients analyzed = 149 and 300 for Placebo and Lixisenatide treatment arm, respectively.
Fasting plasma insulin (FPI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Picomole per liter (pmol/L)
Number Analyzed 285 participants 574 participants 859 participants
66.89  (63.92) 61.34  (52.63) 63.18  (56.61)
[1]
Measure Description: Number of patients analyzed = 152 and 306 for Placebo and Lixisenatide treatment arm, respectively.
2-hour postprandial plasma insulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 285 participants 574 participants 859 participants
281.26  (243.56) 259.44  (182.64) 266.76  (205.09)
[1]
Measure Description: Number of patients analyzed = 154 and 305 for Placebo and Lixisenatide treatment arm, respectively.
Fasting proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 285 participants 574 participants 859 participants
34.39  (32.61) 33.35  (27.43) 33.69  (29.17)
[1]
Measure Description: Number of patients analyzed = 138 and 290 for Placebo and Lixisenatide treatment arm, respectively.
2-hour postprandial proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 285 participants 574 participants 859 participants
61.73  (46.48) 62.12  (44.80) 61.99  (45.31)
[1]
Measure Description: Number of patients analyzed = 130 and 257 for Placebo and Lixisenatide treatment arm, respectively.
Fasting C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 285 participants 574 participants 859 participants
0.89  (0.55) 0.83  (0.43) 0.85  (0.47)
[1]
Measure Description: Number of patients analyzed = 152 and 309 for Placebo and Lixisenatide treatment arm, respectively.
2-hour postprandial C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 285 participants 574 participants 859 participants
2.12  (1.05) 1.99  (0.90) 2.03  (0.95)
[1]
Measure Description: Number of patients analyzed = 152 and 308 for Placebo and Lixisenatide treatment arm, respectively.
Glucose Excursion   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 285 participants 574 participants 859 participants
6.84  (3.78) 6.99  (3.71) 6.94  (3.73)
[1]
Measure Description: Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the meal test, before study drug administration. Number of patients analyzed = 154 and 309 for Placebo and Lixisenatide treatment arms, respectively.
Fasting proinsulin-to-insulin ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 285 participants 574 participants 859 participants
0.62  (0.36) 0.70  (0.57) 0.67  (0.51)
[1]
Measure Description: Number of patients analyzed = 137 and 285 for Placebo and Lixisenatide treatment arm, respectively.
2-hour postprandial proinsulin-to-insulin ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 285 participants 574 participants 859 participants
0.30  (0.22) 0.32  (0.24) 0.31  (0.23)
[1]
Measure Description: Number of patients analyzed = 130 and 253 for Placebo and Lixisenatide treatment arm, respectively.
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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 274 544
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.10  (0.071) -0.85  (0.061)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lixisenatide
Comments To detect a difference of 0.5% (or 0.4%) in change from baseline to Week 24 in HbA1c between lixisenatide and placebo, 570 patients in lixisenatide arm and 285 in placebo arm would provide a power of 99% (or 98%) assuming common standard deviation of 1.3% with a 2-sided test at 5% significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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%), metformin use (yes, no), country as fixed effects, baseline HbA1c as covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-0.867 to -0.621
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
Hide Description The 2-hour PPG blood sample was drawn 2 hours after start of a standardized meal (standardized meal challenge test performed in selected sites). 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. 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
Subgroup for standardized meal test in 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 2-hour PPG assessment during on-treatment period.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 120 249
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.21  (0.489) -6.19  (0.408)
3.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 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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 283 564
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.36  (0.161) -0.99  (0.139)
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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 278 554
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
-0.93  (0.234) -1.76  (0.202)
5.Secondary Outcome
Title Change From Baseline in Beta-cell Function Assessed by HOMA-beta at Week 24
Hide Description Beta cell function was assessed by HOMA-beta. HOMA-beta blood samples were drawn during a standardized meal challenge test (performed in selected sites). 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 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. 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
Subgroup for standardized meal test in 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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 116 241
Least Squares Mean (Standard Error)
Unit of Measure: % of normal beta cells function
6.63  (5.663) 4.83  (4.686)
6.Secondary Outcome
Title Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
Hide Description The fasting glucagon and the 2-hour postprandial glucagon blood samples were drawn during a standardized meal challenge test (performed in selected sites). 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. 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
Subgroup for standardized meal test in mITT population. 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 and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 114 238
Least Squares Mean (Standard Error)
Unit of Measure: ng/L
Fasting glucagon (n=111, 238) 2.03  (2.566) -2.10  (2.081)
2-hour postprandial glucagon (n=114, 234) -1.19  (2.999) -23.33  (2.500)
7.Secondary Outcome
Title Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin at Week 24
Hide Description The fasting plasma insulin and the 2-hour postprandial plasma insulin blood samples were drawn during a standardized meal challenge test (performed in selected sites). 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. 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
Subgroup for standardized meal test in 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 and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 120 244
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
FPI (n=117, 242) 1.42  (6.587) -4.03  (5.445)
2-hour postprandial plasma insulin (n=120, 244) -2.22  (18.754) -67.67  (15.944)
8.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
Hide Description The fasting Proinsulin and the 2-hour postprandial Proinsulin blood samples were drawn during a standardized meal challenge test (performed in selected sites). 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. 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
Subgroup for standardized meal test in mITT population. 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 and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 97 205
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
Fasting proinsulin (n=97, 205) -1.05  (1.983) -6.33  (1.671)
2-hour postprandial proinsulin (n=93, 193) 3.55  (4.200) -4.20  (3.550)
9.Secondary Outcome
Title Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
Hide Description The fasting C-peptide and the 2-hour postprandial C-peptide blood samples were drawn during a standardized meal challenge test (performed in selected sites). 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.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
Subgroup for standardized meal test in mITT population. 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 and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 119 248
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
Fasting C-peptide (n=117, 244) -0.06  (0.038) -0.07  (0.031)
2-hour postprandial C-peptide (n=119, 248) -0.14  (0.087) -0.37  (0.072)
10.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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 274 544
Measure Type: Number
Unit of Measure: percentage of participants
13.5 36.4
11.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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 274 544
Measure Type: Number
Unit of Measure: percentage of participants
4.7 19.3
12.Secondary Outcome
Title Percentage of Patients Requiring Rescue Therapy During 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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 286 570
Measure Type: Number
Unit of Measure: percentage of participants
12.6 4.0
13.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 (performed in selected sites), 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. 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
Subgroup for standardized meal test in 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 glucose excursion assessment during on-treatment period.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 120 249
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
0.35  (0.432) -5.22  (0.360)
14.Other Pre-specified Outcome
Title Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24
Hide Description The fasting proinsulin-to-insulin ratio and 2-hour postprandial proinsulin-to-insulin ratio were measured during a standardized meal challenge test (performed in selected sites). 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. 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
Subgroup for standardized meal test in mITT population. Missing data imputed using LOCF. Number of patients analyzed=patients with baseline and at least 1 post-baseline proinsulin-to-insulin ratio assessment during on-treatment period and 'n'= patients with baseline and at least 1 post-baseline assessment for the specific category.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 95 199
Least Squares Mean (Standard Error)
Unit of Measure: ratio
Fasting proinsulin-to-insulin ratio (n=95, 199) -0.04  (0.049) -0.13  (0.043)
2-hour postprandial ratio (n=92, 190) 0.01  (0.060) 0.16  (0.053)
15.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 Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 278 554
Measure Type: Number
Unit of Measure: percentage of participants
7.2 14.4
16.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, for up to 120 weeks
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.The one patient in the placebo group who received Lixisenatide was analyzed in the Lixisenatide group
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
2-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 285 574
Measure Type: Number
Unit of Measure: participants
Symptomatic hypoglycemia 51 127
Severe symptomatic hypoglycemia 1 2
Time Frame First dose of study drug up to 3 days after the last dose administration, for up to 120 weeks
Adverse Event Reporting Description Median exposure to study treatment was 617 and 610 days in placebo and lixisenatide 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. The one patient in the placebo group who received Lixisenatide was analyzed in the Lixisenatide group
 
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description 2-step initiation regimen of volume matching placebo. 2-step initiation regimen of lixisenatide.
All-Cause Mortality
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   35/285 (12.28%)   58/574 (10.10%) 
Cardiac disorders     
Acute coronary syndrome * 1  1/285 (0.35%)  1/574 (0.17%) 
Acute myocardial infarction * 1  1/285 (0.35%)  2/574 (0.35%) 
Angina pectoris * 1  2/285 (0.70%)  1/574 (0.17%) 
Angina unstable * 1  1/285 (0.35%)  2/574 (0.35%) 
Atrioventricular block complete * 1  0/285 (0.00%)  2/574 (0.35%) 
Cardiac failure congestive * 1  0/285 (0.00%)  1/574 (0.17%) 
Coronary artery disease * 1  1/285 (0.35%)  2/574 (0.35%) 
Coronary artery stenosis * 1  0/285 (0.00%)  1/574 (0.17%) 
Mitral valve incompetence * 1  0/285 (0.00%)  1/574 (0.17%) 
Myocardial infarction * 1  1/285 (0.35%)  2/574 (0.35%) 
Congenital, familial and genetic disorders     
Adenomatous polyposis coli * 1  1/285 (0.35%)  0/574 (0.00%) 
Ear and labyrinth disorders     
Sudden hearing loss * 1  0/285 (0.00%)  2/574 (0.35%) 
Eye disorders     
Cataract * 1  0/285 (0.00%)  1/574 (0.17%) 
Cataract nuclear * 1  0/285 (0.00%)  1/574 (0.17%) 
Vitreous haemorrhage * 1  0/285 (0.00%)  1/574 (0.17%) 
Gastrointestinal disorders     
Colonic polyp * 1  0/285 (0.00%)  1/574 (0.17%) 
Diarrhoea * 1  1/285 (0.35%)  1/574 (0.17%) 
Gastritis * 1  0/285 (0.00%)  1/574 (0.17%) 
Gastrooesophageal reflux disease * 1  0/285 (0.00%)  1/574 (0.17%) 
Haemorrhoids * 1  0/285 (0.00%)  1/574 (0.17%) 
Hiatus hernia * 1  0/285 (0.00%)  1/574 (0.17%) 
Pancreatitis acute * 1  1/285 (0.35%)  1/574 (0.17%) 
Pancreatitis chronic * 1  0/285 (0.00%)  1/574 (0.17%) 
Reflux oesophagitis * 1  0/285 (0.00%)  2/574 (0.35%) 
General disorders     
Chest pain * 1  1/285 (0.35%)  1/574 (0.17%) 
Pyrexia * 1  1/285 (0.35%)  0/574 (0.00%) 
Sudden cardiac death * 1  0/285 (0.00%)  1/574 (0.17%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/285 (0.00%)  2/574 (0.35%) 
Cholelithiasis * 1  0/285 (0.00%)  1/574 (0.17%) 
Hepatitis * 1  0/285 (0.00%)  1/574 (0.17%) 
Hepatitis acute * 1  1/285 (0.35%)  0/574 (0.00%) 
Immune system disorders     
Allergy to arthropod sting * 1  0/285 (0.00%)  1/574 (0.17%) 
Anaphylactic shock * 1  0/285 (0.00%)  1/574 (0.17%) 
Infections and infestations     
Arthritis bacterial * 1  1/285 (0.35%)  0/574 (0.00%) 
Cellulitis * 1  2/285 (0.70%)  0/574 (0.00%) 
Colitis herpes * 1  1/285 (0.35%)  0/574 (0.00%) 
Leptospirosis * 1  0/285 (0.00%)  1/574 (0.17%) 
Pneumonia * 1  1/285 (0.35%)  0/574 (0.00%) 
Pyelonephritis acute * 1  0/285 (0.00%)  1/574 (0.17%) 
Urinary tract infection * 1  1/285 (0.35%)  2/574 (0.35%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  1/285 (0.35%)  1/574 (0.17%) 
Contusion * 1  0/285 (0.00%)  1/574 (0.17%) 
Hand fracture * 1  0/285 (0.00%)  1/574 (0.17%) 
In-stent coronary artery restenosis * 1  1/285 (0.35%)  0/574 (0.00%) 
Lower limb fracture * 1  0/285 (0.00%)  1/574 (0.17%) 
Multiple injuries * 1  0/285 (0.00%)  1/574 (0.17%) 
Muscle injury * 1  1/285 (0.35%)  0/574 (0.00%) 
Patella fracture * 1  0/285 (0.00%)  1/574 (0.17%) 
Periorbital haematoma * 1  0/285 (0.00%)  1/574 (0.17%) 
Pneumothorax traumatic * 1  0/285 (0.00%)  1/574 (0.17%) 
Road traffic accident * 1  0/285 (0.00%)  3/574 (0.52%) 
Investigations     
Blood calcitonin increased * 1  0/285 (0.00%)  1/574 (0.17%) 
Metabolism and nutrition disorders     
Hyperglycaemia * 1  1/285 (0.35%)  0/574 (0.00%) 
Hypoglycaemia * 1  1/285 (0.35%)  1/574 (0.17%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/285 (0.35%)  0/574 (0.00%) 
Intervertebral disc protrusion * 1  2/285 (0.70%)  0/574 (0.00%) 
Rotator cuff syndrome * 1  0/285 (0.00%)  1/574 (0.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm benign * 1  0/285 (0.00%)  1/574 (0.17%) 
Breast cancer * 1  2/285 (0.70%)  0/574 (0.00%) 
Gastric cancer * 1  0/285 (0.00%)  1/574 (0.17%) 
Glottis carcinoma * 1  0/285 (0.00%)  1/574 (0.17%) 
Hepatic neoplasm malignant * 1  1/285 (0.35%)  0/574 (0.00%) 
Prostate cancer * 1  0/285 (0.00%)  1/574 (0.17%) 
Rectal cancer * 1  0/285 (0.00%)  1/574 (0.17%) 
Rectosigmoid cancer * 1  0/285 (0.00%)  1/574 (0.17%) 
Uterine leiomyoma * 1  1/285 (0.35%)  0/574 (0.00%) 
Nervous system disorders     
Cerebral infarction * 1  0/285 (0.00%)  2/574 (0.35%) 
Dizziness * 1  1/285 (0.35%)  0/574 (0.00%) 
Essential tremor * 1  1/285 (0.35%)  0/574 (0.00%) 
Ischaemic stroke * 1  1/285 (0.35%)  1/574 (0.17%) 
Lacunar infarction * 1  1/285 (0.35%)  0/574 (0.00%) 
Transient ischaemic attack * 1  1/285 (0.35%)  2/574 (0.35%) 
VIIth nerve paralysis * 1  1/285 (0.35%)  1/574 (0.17%) 
Psychiatric disorders     
Depression * 1  0/285 (0.00%)  1/574 (0.17%) 
Schizophrenia simple * 1  0/285 (0.00%)  1/574 (0.17%) 
Schizophrenia, paranoid type * 1  0/285 (0.00%)  1/574 (0.17%) 
Renal and urinary disorders     
Calculus ureteric * 1  0/285 (0.00%)  1/574 (0.17%) 
Calculus urinary * 1  1/285 (0.35%)  0/574 (0.00%) 
Renal failure acute * 1  0/285 (0.00%)  1/574 (0.17%) 
Urinary retention * 1  1/285 (0.35%)  0/574 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Hiccups * 1  0/285 (0.00%)  1/574 (0.17%) 
Interstitial lung disease * 1  1/285 (0.35%)  0/574 (0.00%) 
Surgical and medical procedures     
Coronary angioplasty * 1  0/285 (0.00%)  2/574 (0.35%) 
Coronary arterial stent insertion * 1  1/285 (0.35%)  0/574 (0.00%) 
Percutaneous coronary intervention * 1  2/285 (0.70%)  3/574 (0.52%) 
Vascular disorders     
Aortic stenosis * 1  0/285 (0.00%)  1/574 (0.17%) 
Hypertension * 1  1/285 (0.35%)  0/574 (0.00%) 
Peripheral arterial occlusive disease * 1  0/285 (0.00%)  1/574 (0.17%) 
Thrombophlebitis * 1  1/285 (0.35%)  0/574 (0.00%) 
*
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 Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   148/285 (51.93%)   362/574 (63.07%) 
Gastrointestinal disorders     
Constipation * 1  11/285 (3.86%)  30/574 (5.23%) 
Diarrhoea * 1  27/285 (9.47%)  71/574 (12.37%) 
Dyspepsia * 1  4/285 (1.40%)  34/574 (5.92%) 
Nausea * 1  25/285 (8.77%)  161/574 (28.05%) 
Vomiting * 1  15/285 (5.26%)  61/574 (10.63%) 
Infections and infestations     
Influenza * 1  11/285 (3.86%)  30/574 (5.23%) 
Nasopharyngitis * 1  58/285 (20.35%)  91/574 (15.85%) 
Upper respiratory tract infection * 1  21/285 (7.37%)  43/574 (7.49%) 
Investigations     
Blood glucose decreased * 1  11/285 (3.86%)  30/574 (5.23%) 
Metabolism and nutrition disorders     
Hypoglycaemia * 1  55/285 (19.30%)  140/574 (24.39%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  12/285 (4.21%)  36/574 (6.27%) 
Nervous system disorders     
Dizziness * 1  18/285 (6.32%)  60/574 (10.45%) 
Headache * 1  20/285 (7.02%)  44/574 (7.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
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: NCT00713830     History of Changes
Other Study ID Numbers: EFC6015
EudraCT 2007-005881-11
First Submitted: July 10, 2008
First Posted: July 14, 2008
Results First Submitted: August 18, 2016
Results First Posted: December 14, 2016
Last Update Posted: December 14, 2016