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Trial record 45 of 61 for:    Lixisenatide

GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin (GETGOAL-F1)

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ClinicalTrials.gov Identifier: NCT00763451
Recruitment Status : Completed
First Posted : October 1, 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: Metformin
Enrollment 484
Recruitment Details The study was conducted at 75 centers in 15 countries between September 29, 2008 and January 27, 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 884 patients were screened of which 400 (45.2%) 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 percent [%] and less than or equal to 10%). A total of 484 patients were randomized.
Arm/Group Title Placebo (Two-Step Titration) Placebo (One-Step Titration) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
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. 1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, 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. 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment.
Period Title: Overall Study
Started 80 [1] 82 161 161
Treated/Safety Population 79 [2] 81 161 161
Modified Intent-to-Treat(mITT)Population 79 [3] 80 160 160
Completed 67 60 121 131
Not Completed 13 22 40 30
Reason Not Completed
Adverse Event             4             6             19             14
Lack of Efficacy             1             4             3             2
Withdrawal by Subject             1             6             9             7
Protocol Violation             0             0             1             0
Poor Compliance to Protocol             1             1             2             2
Familial and Personal Reasons             5             3             5             4
Randomized but not Treated             1             1             0             0
Study Site Reason             0             1             1             1
[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.
Arm/Group Title Placebo (Two-step Titration) Placebo (One-step Titration) Lixisenatide (Two-step Titration) Lixisenatide (One-step Titration) Total
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. 1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, 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. 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment. Total of all reporting groups
Overall Number of Baseline Participants 79 81 161 161 482
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 79 participants 81 participants 161 participants 161 participants 482 participants
58.9  (8.8) 57.5  (10.8) 54.6  (8.9) 55.4  (8.9) 56.1  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
Female
43
  54.4%
45
  55.6%
89
  55.3%
90
  55.9%
267
  55.4%
Male
36
  45.6%
36
  44.4%
72
  44.7%
71
  44.1%
215
  44.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
Race: Caucasian/White 72 76 146 141 435
Race: Black 0 1 2 1 4
Race: Asian/Oriental 5 4 11 13 33
Race: Other 2 0 2 6 10
Ethnicity: Hispanic 24 22 55 44 145
Ethnicity: Non Hispanic 55 59 106 117 337
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
8.03  (0.81) 8.02  (0.84) 8.10  (0.88) 7.99  (0.87) 8.04  (0.86)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  Millimole per liter (mmol/L)
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
9.60  (2.06) 9.31  (1.82) 9.54  (2.50) 9.56  (2.02) 9.52  (2.17)
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
87.45  (16.32) 88.28  (18.43) 87.41  (16.90) 90.21  (18.95) 88.50  (17.77)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
6.68  (5.33) 5.77  (4.00) 6.01  (4.60) 5.77  (3.85) 6.00  (4.40)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 79 participants 81 participants 161 participants 161 participants 482 participants
32.38  (5.04) 32.35  (5.86) 32.06  (4.84) 32.99  (5.80) 32.47  (5.38)
[1]
Measure Description: BMI was calculated by dividing body weight (kilogram) by the height (meter) squared.
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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol

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 (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 152 156
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.42  (0.099) -0.83  (0.099) -0.92  (0.101)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Combined), Lixisenatide (Two-Step Titration)
Comments

To detect a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.

Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (<8.0,>=8.0%) and screening 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 (2-step titration) was compared with Placebo (combined), if found statistically significant, then Lixisenatide (1-step titration) arm compared with Placebo (combined).
Method ANCOVA
Comments Threshold for significance at 0,05 level
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.583 to -0.232
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.089
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Combined), Lixisenatide (One-Step Titration)
Comments

To detect a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.

Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (<8.0,>=8.0%) and screening 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 (2-step titration) was compared with Placebo (combined), if found statistically significant, then Lixisenatide (1-step titration) arm compared with Placebo (combined).
Method ANCOVA
Comments Threshold for significance at 0,05 level
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.670 to -0.317
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.090
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.The "Placebo (Two-step Titration)"and"Placebo (One-step Titration)"Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 160 158
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
0.11  (0.209) -0.56  (0.208) -0.53  (0.212)
3.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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 155 158
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
-1.63  (0.385) -2.68  (0.385) -2.63  (0.389)
4.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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 152 156
Measure Type: Number
Unit of Measure: percentage of participants
24.1 42.1 47.4
5.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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 152 156
Measure Type: Number
Unit of Measure: percentage of participants
7.6 20.4 25.6
6.Secondary Outcome
Title Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Hide Description Routine fasting self-measured 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. The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 159 160 160
Measure Type: Number
Unit of Measure: percentage of participants
4.4 3.1 1.3
7.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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 158 155 158
Measure Type: Number
Unit of Measure: percentage of participants
15.2 25.8 19.6
8.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 112 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 "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Arm/Group Title Placebo (Combined) Lixisenatide (Two-Step Titration) Lixisenatide (One-Step Titration)
Hide Arm/Group Description:
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
2-step initiation regimen of lixisenatide.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 160 161 161
Measure Type: Number
Unit of Measure: participants
Symptomatic hypoglycemia 12 12 6
Severe symptomatic hypoglycemia 0 0 0
Time Frame First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks
Adverse Event Reporting Description Median exposure to study treatment was 567, 588 and 589 days in lixisenatide two step titration, one step titration and placebo combined 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 (Two-step Titration) Placebo (One-step Titration) Placebo (Combined) Lixisenatide (Two-step Titration) Lixisenatide One-step Titration Lixisenatide (Combined)
Hide Arm/Group Description 2-step initiation regimen of volume matching placebo. 1-step initiation regimen of volume matching placebo. Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo. 2-step initiation regimen of lixisenatide. 1-step initiation regimen of lixisenatide. Included all patients who received 2-step initiation regimen of lixisenatide and 1-step initiation regimen of lixisenatide.
All-Cause Mortality
Placebo (Two-step Titration) Placebo (One-step Titration) Placebo (Combined) Lixisenatide (Two-step Titration) Lixisenatide One-step Titration 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 (Two-step Titration) Placebo (One-step Titration) Placebo (Combined) Lixisenatide (Two-step Titration) Lixisenatide One-step Titration Lixisenatide (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/79 (16.46%)   9/81 (11.11%)   22/160 (13.75%)   21/161 (13.04%)   16/161 (9.94%)   37/322 (11.49%) 
Cardiac disorders             
Acute myocardial infarction * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  2/161 (1.24%)  2/322 (0.62%) 
Adams-Stokes syndrome * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Angina unstable * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Atrial fibrillation * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  1/161 (0.62%)  1/161 (0.62%)  2/322 (0.62%) 
Bradycardia * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Coronary artery disease * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Coronary artery stenosis * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Myocardial infarction * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Myocardial ischaemia * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Endocrine disorders             
Goitre * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Hypothyroidism * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Eye disorders             
Retinal detachment * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Gastrointestinal disorders             
Constipation * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Gastritis * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Inguinal hernia * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Irritable bowel syndrome * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Nausea * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Vomiting * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Hepatobiliary disorders             
Cholecystitis * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Cholecystitis acute * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Infections and infestations             
Appendicitis * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Bronchitis * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Dengue fever * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Hepatitis B * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Lobar pneumonia * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Peritonsillar abscess * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Pneumonia * 1  1/79 (1.27%)  1/81 (1.23%)  2/160 (1.25%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Septic shock * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Soft tissue infection * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Injury, poisoning and procedural complications             
Ankle fracture * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Fall * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Incisional hernia * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Meniscus lesion * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Multiple injuries * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Rib fracture * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Skin laceration * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Spinal fracture * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Sternal fracture * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Wrist fracture * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Investigations             
Blood calcitonin increased * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Pancreatic enzymes increased * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Metabolism and nutrition disorders             
Diabetes mellitus * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  2/161 (1.24%)  0/161 (0.00%)  2/322 (0.62%) 
Musculoskeletal and connective tissue disorders             
Arthropathy * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Back pain * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Osteoarthritis * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Osteochondrosis * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Bladder cancer * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Breast cancer * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Ovarian cancer * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Pancreatic carcinoma * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Renal neoplasm * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  1/161 (0.62%)  2/322 (0.62%) 
Nervous system disorders             
Cerebral infarction * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  2/161 (1.24%)  0/161 (0.00%)  2/322 (0.62%) 
Cerebrovascular accident * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Coma * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Diabetic neuropathy * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Haemorrhagic stroke * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Ischaemic stroke * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Polyneuropathy * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Ruptured cerebral aneurysm * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Psychiatric disorders             
Depression * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  1/161 (0.62%)  0/161 (0.00%)  1/322 (0.31%) 
Respiratory, thoracic and mediastinal disorders             
Pulmonary oedema * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis allergic * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
Surgical and medical procedures             
Coronary arterial stent insertion * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  0/161 (0.00%)  0/161 (0.00%)  0/322 (0.00%) 
Vascular disorders             
Hypertension * 1  0/79 (0.00%)  0/81 (0.00%)  0/160 (0.00%)  0/161 (0.00%)  1/161 (0.62%)  1/322 (0.31%) 
*
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 (Two-step Titration) Placebo (One-step Titration) Placebo (Combined) Lixisenatide (Two-step Titration) Lixisenatide One-step Titration Lixisenatide (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   51/79 (64.56%)   53/81 (65.43%)   104/160 (65.00%)   119/161 (73.91%)   101/161 (62.73%)   220/322 (68.32%) 
Gastrointestinal disorders             
Abdominal pain * 1  3/79 (3.80%)  4/81 (4.94%)  7/160 (4.38%)  9/161 (5.59%)  8/161 (4.97%)  17/322 (5.28%) 
Constipation * 1  3/79 (3.80%)  0/81 (0.00%)  3/160 (1.88%)  11/161 (6.83%)  2/161 (1.24%)  13/322 (4.04%) 
Diarrhoea * 1  10/79 (12.66%)  11/81 (13.58%)  21/160 (13.13%)  24/161 (14.91%)  16/161 (9.94%)  40/322 (12.42%) 
Dyspepsia * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  7/161 (4.35%)  9/161 (5.59%)  16/322 (4.97%) 
Gastritis * 1  4/79 (5.06%)  0/81 (0.00%)  4/160 (2.50%)  8/161 (4.97%)  7/161 (4.35%)  15/322 (4.66%) 
Nausea * 1  8/79 (10.13%)  5/81 (6.17%)  13/160 (8.13%)  61/161 (37.89%)  47/161 (29.19%)  108/322 (33.54%) 
Vomiting * 1  1/79 (1.27%)  0/81 (0.00%)  1/160 (0.63%)  29/161 (18.01%)  21/161 (13.04%)  50/322 (15.53%) 
General disorders             
Asthenia * 1  0/79 (0.00%)  1/81 (1.23%)  1/160 (0.63%)  9/161 (5.59%)  3/161 (1.86%)  12/322 (3.73%) 
Oedema peripheral * 1  4/79 (5.06%)  3/81 (3.70%)  7/160 (4.38%)  3/161 (1.86%)  3/161 (1.86%)  6/322 (1.86%) 
Infections and infestations             
Bronchitis * 1  6/79 (7.59%)  7/81 (8.64%)  13/160 (8.13%)  3/161 (1.86%)  7/161 (4.35%)  10/322 (3.11%) 
Gastroenteritis * 1  7/79 (8.86%)  2/81 (2.47%)  9/160 (5.63%)  4/161 (2.48%)  7/161 (4.35%)  11/322 (3.42%) 
Influenza * 1  9/79 (11.39%)  9/81 (11.11%)  18/160 (11.25%)  20/161 (12.42%)  11/161 (6.83%)  31/322 (9.63%) 
Nasopharyngitis * 1  13/79 (16.46%)  8/81 (9.88%)  21/160 (13.13%)  16/161 (9.94%)  18/161 (11.18%)  34/322 (10.56%) 
Pharyngitis * 1  6/79 (7.59%)  6/81 (7.41%)  12/160 (7.50%)  9/161 (5.59%)  10/161 (6.21%)  19/322 (5.90%) 
Upper respiratory tract infection * 1  4/79 (5.06%)  5/81 (6.17%)  9/160 (5.63%)  4/161 (2.48%)  6/161 (3.73%)  10/322 (3.11%) 
Urinary tract infection * 1  6/79 (7.59%)  5/81 (6.17%)  11/160 (6.88%)  11/161 (6.83%)  10/161 (6.21%)  21/322 (6.52%) 
Metabolism and nutrition disorders             
Hyperuricaemia * 1  4/79 (5.06%)  0/81 (0.00%)  4/160 (2.50%)  1/161 (0.62%)  4/161 (2.48%)  5/322 (1.55%) 
Hypoglycaemia * 1 [1]  8/79 (10.13%)  5/81 (6.17%)  13/160 (8.13%)  12/161 (7.45%)  6/161 (3.73%)  18/322 (5.59%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  9/79 (11.39%)  5/81 (6.17%)  14/160 (8.75%)  11/161 (6.83%)  9/161 (5.59%)  20/322 (6.21%) 
Back pain * 1  8/79 (10.13%)  3/81 (3.70%)  11/160 (6.88%)  15/161 (9.32%)  18/161 (11.18%)  33/322 (10.25%) 
Myalgia * 1  4/79 (5.06%)  4/81 (4.94%)  8/160 (5.00%)  2/161 (1.24%)  4/161 (2.48%)  6/322 (1.86%) 
Osteoarthritis * 1  4/79 (5.06%)  2/81 (2.47%)  6/160 (3.75%)  4/161 (2.48%)  5/161 (3.11%)  9/322 (2.80%) 
Pain in extremity * 1  5/79 (6.33%)  3/81 (3.70%)  8/160 (5.00%)  4/161 (2.48%)  3/161 (1.86%)  7/322 (2.17%) 
Nervous system disorders             
Dizziness * 1  11/79 (13.92%)  10/81 (12.35%)  21/160 (13.13%)  19/161 (11.80%)  15/161 (9.32%)  34/322 (10.56%) 
Headache * 1  11/79 (13.92%)  9/81 (11.11%)  20/160 (12.50%)  23/161 (14.29%)  20/161 (12.42%)  43/322 (13.35%) 
Vascular disorders             
Hypertension * 1  2/79 (2.53%)  10/81 (12.35%)  12/160 (7.50%)  12/161 (7.45%)  9/161 (5.59%)  21/322 (6.52%) 
*
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: NCT00763451     History of Changes
Other Study ID Numbers: EFC10743
2008-001002-16 ( EudraCT Number )
First Submitted: September 30, 2008
First Posted: October 1, 2008
Results First Submitted: August 18, 2016
Results First Posted: December 14, 2016
Last Update Posted: December 14, 2016