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Trial record 37 of 61 for:    Lixisenatide

24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years

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ClinicalTrials.gov Identifier: NCT00976937
Recruitment Status : Completed
First Posted : September 15, 2009
Results First Posted : October 11, 2016
Last Update Posted : October 11, 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 Type 2 Diabetes Mellitus
Interventions Drug: Lixisenatide (AVE0010)
Drug: Lixisenatide Placebo
Device: Pen auto-injector
Drug: Sitagliptin
Drug: Sitagliptin Placebo
Drug: Metformin
Enrollment 319
Recruitment Details The study was conducted at 92 centers in 13 countries between August 31, 2009 and March 19, 2011.
Pre-assignment Details A total of 620 patients were screened of which 301 (48.5%) 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 319 patients were randomized.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24. Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.
Period Title: Overall Study
Started 158 [1] 161
Treated/Safety Population 158 [2] 161
Modified Intent-to-Treat(mITT)Population 158 [3] 161
Completed 142 150
Not Completed 16 11
Reason Not Completed
Adverse Event             4             5
Lost to Follow-up             2             1
Withdrawal by Subject             5             3
Poor compliance to protocol             3             0
Personal and Familial Reason             2             2
[1]
Randomized
[2]
All patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
[3]
All randomized patients who received at least 1 dose of study drug.
Arm/Group Title Lixisenatide Sitagliptin Total
Hide Arm/Group Description 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 mg capsule orally QD up to Week 24. Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Total of all reporting groups
Overall Number of Baseline Participants 158 161 319
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 158 participants 161 participants 319 participants
42.7  (5.2) 43.4  (4.7) 43.1  (4.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 158 participants 161 participants 319 participants
Female
103
  65.2%
88
  54.7%
191
  59.9%
Male
55
  34.8%
73
  45.3%
128
  40.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 158 participants 161 participants 319 participants
Race: Caucasian/White 132 127 259
Race: Black 8 11 19
Race: Asian/Oriental 1 1 2
Race: Other 17 22 39
Ethnicity: Hispanic 73 72 145
Ethnicity: Non Hispanic 85 89 174
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 158 participants 161 participants 319 participants
8.16  (0.89) 8.09  (0.96) 8.12  (0.93)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 158 participants 161 participants 319 participants
36.76  (7.25) 36.76  (6.34) 36.76  (6.80)
[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 158 participants 161 participants 319 participants
4.40  (3.86) 4.43  (3.56) 4.42  (3.70)
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 158 participants 161 participants 319 participants
98.51  (23.48) 100.56  (23.77) 99.55  (23.61)
2-hour Postprandial Plasma Glucose (PPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  Millimole per liter (mmol/L)
Number Analyzed 158 participants 161 participants 319 participants
13.77  (3.78) 13.92  (3.99) 13.84  (3.88)
[1]
Measure Description: The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Number of patients analyzed = 158 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 158 participants 161 participants 319 participants
9.09  (2.60) 8.96  (2.59) 9.03  (2.59)
Glucose Excursion   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 158 participants 161 participants 319 participants
4.37  (2.64) 4.48  (2.59) 4.42  (2.61)
[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 = 157 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Plasma Insulin (FPI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Picomole/liter (pmol/L)
Number Analyzed 158 participants 161 participants 319 participants
108.56  (82.03) 106.99  (82.69) 107.76  (82.23)
[1]
Measure Description: Here, number of patients analyzed = 149 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Plasma Insulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 158 participants 161 participants 319 participants
424.67  (350.96) 420.45  (302.17) 422.56  (327.02)
[1]
Measure Description: Here, number of patients analyzed = 152 and 151 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting C-Peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 158 participants 161 participants 319 participants
1.19  (0.51) 1.20  (0.52) 1.20  (0.52)
[1]
Measure Description: Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 158 participants 161 participants 319 participants
2.79  (1.28) 2.92  (1.35) 2.86  (1.32)
[1]
Measure Description: Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  Nanogram/liter (ng/L)
Number Analyzed 158 participants 161 participants 319 participants
59.12  (15.81) 59.43  (20.53) 59.28  (18.32)
[1]
Measure Description: Here, number of patients analyzed = 154 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Glucagon   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/L
Number Analyzed 158 participants 161 participants 319 participants
66.36  (17.58) 67.72  (25.77) 67.04  (22.05)
[1]
Measure Description: Here, number of patients analyzed = 154 and 155 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 158 participants 161 participants 319 participants
45.06  (39.50) 44.62  (36.42) 44.83  (37.91)
[1]
Measure Description: Here, number of patients analyzed = 154 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Proinsulin   [1] 
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 158 participants 161 participants 319 participants
105.50  (75.38) 105.51  (74.00) 105.51  (74.57)
[1]
Measure Description: Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Proinsulin-to-Insulin Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 158 participants 161 participants 319 participants
0.53  (0.70) 0.59  (0.73) 0.56  (0.71)
[1]
Measure Description: Here, number of patients analyzed = 149 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Proinsulin-to-Insulin Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 158 participants 161 participants 319 participants
0.36  (0.53) 0.32  (0.24) 0.34  (0.41)
[1]
Measure Description: Here, number of patients analyzed = 152 and 151 for lixisenatide and sitagliptin treatment arm, respectively.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliunit * mmol /liter^2(mU * mmol/L^2)
Number Analyzed 158 participants 161 participants 319 participants
6.30  (5.08) 6.26  (5.32) 6.28  (5.20)
[1]
Measure Description: HOMA-IR was derived from FPG and FPI as: (FPI [micro units per milliliter] * FPG [mmol/L]) divided by 22.5. Here, number of patients analyzed = 148 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
Homeostatic Model Assessment of Beta-cell Function (HOMA-beta)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of normal beta cells function
Number Analyzed 158 participants 161 participants 319 participants
62.01  (59.78) 60.74  (50.80) 61.36  (55.29)
[1]
Measure Description: HOMA-beta was derived from FPG and FPI as: (20 * FPI [micro units/milliliter]) divided by (FPG [mmol/L] minus 3.5). Here, number of patients analyzed = 148 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
1.Primary Outcome
Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
Hide Description Percentage of patients who met both criteria (HbA1c <7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included randomized patients who received at least 1 dose of study drug. Missing data was imputed using Last observation carried forward (LOCF).
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 158 161
Measure Type: Number
Unit of Measure: percentage of participants
12.0 7.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lixisenatide, Sitagliptin
Comments To demonstrate the superiority of lixisenatide over sitagliptin, 150 patients in each arm would provide a power of 90% with a 2-sided test at the 5% significance level, assuming the percentage of patients defined as responders on HbA1c (<7%) and weight (at least 5% loss) is 25% with lixisenatide and 10% with sitagliptin.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1696
Comments Cochran-Mantel-Haenszel (CMH) test stratified by randomization strata of screening HbA1c (<8.0 or >=8.0%) and randomization strata of screening BMI (<35 or >=35 kg/m^2) was used.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Response rate difference
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-1.84 to 11.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.28
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Absolute Change From Baseline in 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 the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 HbA1c assessment during on-treatment period.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 150 160
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.66  (0.094) -0.72  (0.097)
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 the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 152 160
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
-2.51  (0.294) -1.17  (0.304)
4.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. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 2-hour PPG assessment during on-treatment period.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 129 139
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.35  (0.377) -1.44  (0.384)
5.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 the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 153 161
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.45  (0.193) -0.69  (0.198)
6.Secondary 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 the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 glucose excursion assessment during on-treatment period.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 127 139
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-2.55  (0.272) -0.42  (0.275)
7.Secondary Outcome
Title Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24
Hide Description Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 123 133
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
FPI (n=119, 133) -1.70  (6.789) -0.88  (7.020)
2-hour PPI (n=123, 130) -57.81  (22.788) -2.85  (23.309)
8.Secondary Outcome
Title Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
Hide Description Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 125 139
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
Fasting C-peptide (n= 123,139) -0.02  (0.039) -0.02  (0.038)
2-hour postprandial C-peptide (n=125, 139) -0.15  (0.100) 0.08  (0.101)
9.Secondary Outcome
Title Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
Hide Description Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 124 138
Least Squares Mean (Standard Error)
Unit of Measure: ng/L
Fasting Glucagon (n=124, 138) 1.89  (1.667) 3.52  (1.661)
2-hour postprandial Glucagon (n=124, 134) -8.16  (1.801) -4.38  (1.824)
10.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
Hide Description Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 125 140
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
Fasting Proinsulin (n=125, 140) -2.18  (3.172) -4.84  (3.154)
2-hour postprandial Proinsulin (n=125, 139) 0.28  (6.502) -3.95  (6.477)
11.Secondary Outcome
Title Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24
Hide Description HOMA-IR was derived from FPG and FPI as: (FPI [micro units per milliliter]*FPG [mmol/L]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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-IR assessment during on-treatment period.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 118 133
Least Squares Mean (Standard Error)
Unit of Measure: mU * mmol/L^2
-0.52  (0.366) -0.57  (0.378)
12.Secondary Outcome
Title Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment–Beta (HOMA-beta) at Week 24
Hide Description HOMA-beta was derived from FPG and FPI as: (20*FPI [micro units/milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated for HOMA-beta by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 118 133
Least Squares Mean (Standard Error)
Unit of Measure: percentage of normal beta cells function
17.66  (9.652) 17.79  (9.958)
13.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 the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 150 160
Measure Type: Number
Unit of Measure: percentage of participants
24.0 26.3
14.Secondary Outcome
Title Percentage of Patients Requiring Rescue Therapy During 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%.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 158 161
Measure Type: Number
Unit of Measure: percentage of participants
9.5 6.8
15.Other Pre-specified 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 the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 150 160
Measure Type: Number
Unit of Measure: percentage of participants
40.7 40.0
16.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 the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 152 160
Measure Type: Number
Unit of Measure: percentage of participants
18.4 11.9
17.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 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
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 proinsulin-to-insulin ratio assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.
Arm/Group Title Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 123 133
Least Squares Mean (Standard Error)
Unit of Measure: ratio
Fasting Proinsulin-to-insulin ratio (n=119, 133) -0.08  (0.035) -0.17  (0.036)
2-hour PP Proinsulin-to-insulin ratio (n=123, 130) -0.01  (0.025) -0.05  (0.026)
18.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 Lixisenatide Sitagliptin
Hide Arm/Group Description:
2-step initiation regimen of lixisenatide along with sitagliptin placebo.
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Overall Number of Participants Analyzed 158 161
Measure Type: Number
Unit of Measure: participants
Symptomatic hypoglycemia 1 3
Severe symptomatic hypoglycemia 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 was 169.0 days in both lixisenatide and sitagliptin treatment arm. 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 Lixisenatide Sitagliptin
Hide Arm/Group Description 2-step initiation regimen of lixisenatide along with sitagliptin placebo. Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
All-Cause Mortality
Lixisenatide Sitagliptin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lixisenatide Sitagliptin
Affected / at Risk (%) Affected / at Risk (%)
Total   3/158 (1.90%)   3/161 (1.86%) 
Hepatobiliary disorders     
Bile duct stone * 1  0/158 (0.00%)  1/161 (0.62%) 
Immune system disorders     
Anaphylactic reaction * 1  1/158 (0.63%)  0/161 (0.00%) 
Infections and infestations     
Abscess limb * 1  0/158 (0.00%)  1/161 (0.62%) 
Renal and urinary disorders     
Nephrolithiasis * 1  1/158 (0.63%)  0/161 (0.00%) 
Renal failure * 1  0/158 (0.00%)  1/161 (0.62%) 
Vascular disorders     
Arteriovenous fistula * 1  1/158 (0.63%)  0/161 (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%
Lixisenatide Sitagliptin
Affected / at Risk (%) Affected / at Risk (%)
Total   54/158 (34.18%)   45/161 (27.95%) 
Gastrointestinal disorders     
Diarrhoea * 1  14/158 (8.86%)  12/161 (7.45%) 
Nausea * 1  28/158 (17.72%)  11/161 (6.83%) 
Infections and infestations     
Influenza * 1  8/158 (5.06%)  5/161 (3.11%) 
Nasopharyngitis * 1  10/158 (6.33%)  12/161 (7.45%) 
Nervous system disorders     
Dizziness * 1  8/158 (5.06%)  5/161 (3.11%) 
Headache * 1  20/158 (12.66%)  15/161 (9.32%) 
*
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: NCT00976937     History of Changes
Other Study ID Numbers: EFC10780
EudraCT:2008-007 334-22
First Submitted: September 14, 2009
First Posted: September 15, 2009
Results First Submitted: August 18, 2016
Results First Posted: October 11, 2016
Last Update Posted: October 11, 2016