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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00976937
First received: September 14, 2009
Last updated: August 18, 2016
Last verified: August 2016
Results First Received: August 18, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, 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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 92 centers in 13 countries between August 31, 2009 and March 19, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Lixisenatide 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 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.

Participant Flow:   Overall Study
    Lixisenatide   Sitagliptin
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 
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Reporting Groups
  Description
Lixisenatide 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 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 Total of all reporting groups

Baseline Measures
   Lixisenatide   Sitagliptin   Total 
Overall Participants Analyzed 
[Units: Participants]
 158   161   319 
Age 
[Units: Years]
Mean (Standard Deviation)
 42.7  (5.2)   43.4  (4.7)   43.1  (4.9) 
Gender 
[Units: Participants]
     
Female   103   88   191 
Male   55   73   128 
Race/Ethnicity, Customized 
[Units: 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) 
[Units: Percentage of hemoglobin]
Mean (Standard Deviation)
 8.16  (0.89)   8.09  (0.96)   8.12  (0.93) 
Body Mass Index (BMI) [1] 
[Units: Kilogram per square meter (kg/m^2)]
Mean (Standard Deviation)
 36.76  (7.25)   36.76  (6.34)   36.76  (6.80) 
[1] BMI was calculated by dividing body weight by the height squared.
Duration of Diabetes 
[Units: Years]
Mean (Standard Deviation)
 4.40  (3.86)   4.43  (3.56)   4.42  (3.70) 
Body Weight 
[Units: Kilogram]
Mean (Standard Deviation)
 98.51  (23.48)   100.56  (23.77)   99.55  (23.61) 
2-hour Postprandial Plasma Glucose (PPG) [1] 
[Units: Millimole per liter (mmol/L)]
Mean (Standard Deviation)
 13.77  (3.78)   13.92  (3.99)   13.84  (3.88) 
[1] 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) 
[Units: mmol/L]
Mean (Standard Deviation)
 9.09  (2.60)   8.96  (2.59)   9.03  (2.59) 
Glucose Excursion [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 4.37  (2.64)   4.48  (2.59)   4.42  (2.61) 
[1] 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] 
[Units: Picomole/liter (pmol/L)]
Mean (Standard Deviation)
 108.56  (82.03)   106.99  (82.69)   107.76  (82.23) 
[1] Here, number of patients analyzed = 149 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Plasma Insulin [1] 
[Units: pmol/L]
Mean (Standard Deviation)
 424.67  (350.96)   420.45  (302.17)   422.56  (327.02) 
[1] Here, number of patients analyzed = 152 and 151 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting C-Peptide [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 1.19  (0.51)   1.20  (0.52)   1.20  (0.52) 
[1] Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial C-peptide [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 2.79  (1.28)   2.92  (1.35)   2.86  (1.32) 
[1] Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Glucagon [1] 
[Units: Nanogram/liter (ng/L)]
Mean (Standard Deviation)
 59.12  (15.81)   59.43  (20.53)   59.28  (18.32) 
[1] Here, number of patients analyzed = 154 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Glucagon [1] 
[Units: ng/L]
Mean (Standard Deviation)
 66.36  (17.58)   67.72  (25.77)   67.04  (22.05) 
[1] Here, number of patients analyzed = 154 and 155 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Proinsulin [1] 
[Units: pmol/L]
Mean (Standard Deviation)
 45.06  (39.50)   44.62  (36.42)   44.83  (37.91) 
[1] Here, number of patients analyzed = 154 and 157 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Proinsulin [1] 
[Units: pmol/L]
Mean (Standard Deviation)
 105.50  (75.38)   105.51  (74.00)   105.51  (74.57) 
[1] Here, number of patients analyzed = 154 and 156 for lixisenatide and sitagliptin treatment arm, respectively.
Fasting Proinsulin-to-Insulin Ratio [1] 
[Units: Ratio]
Mean (Standard Deviation)
 0.53  (0.70)   0.59  (0.73)   0.56  (0.71) 
[1] Here, number of patients analyzed = 149 and 154 for lixisenatide and sitagliptin treatment arm, respectively.
2-hour Postprandial Proinsulin-to-Insulin Ratio [1] 
[Units: Ratio]
Mean (Standard Deviation)
 0.36  (0.53)   0.32  (0.24)   0.34  (0.41) 
[1] Here, number of patients analyzed = 152 and 151 for lixisenatide and sitagliptin treatment arm, respectively.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [1] 
[Units: Milliunit * mmol /liter^2(mU * mmol/L^2)]
Mean (Standard Deviation)
 6.30  (5.08)   6.26  (5.32)   6.28  (5.20) 
[1] 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] 
[Units: Percentage of normal beta cells function]
Mean (Standard Deviation)
 62.01  (59.78)   60.74  (50.80)   61.36  (55.29) 
[1] 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.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24   [ Time Frame: Week 24 ]

2.  Secondary:   Absolute Change From Baseline in HbA1c at Week 24   [ Time Frame: Baseline, Week 24 ]

3.  Secondary:   Change From Baseline in Body Weight at Week 24   [ Time Frame: Baseline, Week 24 ]

4.  Secondary:   Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24   [ Time Frame: Baseline, Week 24 ]

5.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24   [ Time Frame: Baseline, Week 24 ]

6.  Secondary:   Change From Baseline in Glucose Excursion at Week 24   [ Time Frame: Baseline, Week 24 ]

7.  Secondary:   Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24   [ Time Frame: Baseline, Week 24 ]

8.  Secondary:   Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24   [ Time Frame: Baseline, Week 24 ]

9.  Secondary:   Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24   [ Time Frame: Baseline, Week 24 ]

10.  Secondary:   Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24   [ Time Frame: Baseline, Week 24 ]

11.  Secondary:   Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24   [ Time Frame: Baseline, Week 24 ]

12.  Secondary:   Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment–Beta (HOMA-beta) at Week 24   [ Time Frame: Baseline, Week 24 ]

13.  Secondary:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24   [ Time Frame: Week 24 ]

14.  Secondary:   Percentage of Patients Requiring Rescue Therapy During 24-Week Period   [ Time Frame: Baseline up to Week 24 ]

15.  Other Pre-specified:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24   [ Time Frame: Week 24 ]

16.  Other Pre-specified:   Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

17.  Other Pre-specified:   Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24   [ Time Frame: Baseline, Week 24 ]

18.  Other Pre-specified:   Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia   [ Time Frame: First dose of study drug up to 3 days after the last dose administration ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-us@sanofi.com



Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00976937     History of Changes
Other Study ID Numbers: EFC10780
EudraCT:2008-007 334-22
Study First Received: September 14, 2009
Results First Received: August 18, 2016
Last Updated: August 18, 2016
Health Authority: United States: Food and Drug Administration