24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine (GetGoal-Duo1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00975286
First received: September 10, 2009
Last updated: August 18, 2016
Last verified: August 2016
Results First Received: August 18, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Lixisenatide (AVE0010)
Drug: Placebo
Drug: Insulin glargine
Device: Pen auto-injector
Drug: Metformin
Drug: Thiazolidinedione (TZD)

  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 140 centers in 25 countries between October 13, 2009 and August 01, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1470 patients were screened of which 1024 were screen or run-in 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 9%). A total of 446 patients were randomized.

Reporting Groups
  Description
Placebo 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 Week 24.
Lixisenatide 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 Week 24.

Participant Flow:   Overall Study
    Placebo   Lixisenatide
STARTED   223 [1]   223 
Safety Population   223 [2]   223 
Modified Intent-to-Treat(mITT)Population   223 [3]   223 
COMPLETED   211   194 
NOT COMPLETED   12   29 
Adverse Event                9                19 
Protocol Violation                1                2 
Withdrawal by Subject                0                2 
Familial and Personal Reasons                2                2 
Poor Compliance to Protocol                0                2 
Sponsor Decision                0                2 
[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.



  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
Placebo 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 Week 24.
Lixisenatide 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 Week 24.
Total Total of all reporting groups

Baseline Measures
   Placebo   Lixisenatide   Total 
Overall Participants Analyzed 
[Units: Participants]
 223   223   446 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 56.1  (10.2)   56.4  (9.7)   56.2  (9.9) 
[1] Age at screening is reported.
Gender 
[Units: Participants]
     
Female   110   114   224 
Male   113   109   222 
Race/Ethnicity, Customized 
[Units: Participants]
     
Race: Caucasian/White   167   165   332 
Race: Black   11   9   20 
Race: Asian/Oriental   43   44   87 
Race: Other   2   5   7 
Ethnicity: Hispanic   49   52   101 
Ethnicity: Non Hispanic   174   171   345 
Glycosylated Hemoglobin (HbA1c) 
[Units: Percentage of hemoglobin]
Mean (Standard Deviation)
 7.60  (0.54)   7.56  (0.55)   7.58  (0.54) 
Fasting Plasma Glucose (FPG) 
[Units: Millimole per liter (mmol/L)]
Mean (Standard Deviation)
 6.70  (1.97)   6.55  (1.72)   6.62  (1.85) 
2-Hour Postprandial Plasma Glucose (PPG) [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 12.79  (3.69)   12.90  (3.94)   12.85  (3.81) 
[1] The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Number of patients evaluable for this Baseline characteristic were 221 and 219 for Placebo and Lixisenatide arm, respectively.
Glucose Excursion [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 6.33  (3.54)   6.24  (4.35)   6.29  (3.96) 
[1] Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the meal test, before study drug administration. Number of patients evaluable for this Baseline characteristic were 221 and 219 for Placebo and Lixisenatide arm, respectively.
Average 7-Point Self Monitored Plasma Glucose (SMPG) [1] 
[Units: mmol/L]
Mean (Standard Deviation)
 8.26  (1.52)   8.20  (1.47)   8.23  (1.49) 
[1] Patients recorded a 7-point plasma glucose profile before and 2 hours after each meal and at bedtime once in a week and the average value for the 7-time points was calculated. Number of patients evaluable for this Baseline characteristic were 221 and 221 for Placebo and Lixisenatide arm, respectively.
Body Weight 
[Units: Kilogram (kg)]
Mean (Standard Deviation)
 86.75  (20.41)   87.31  (21.76)   87.03  (21.07) 
Average Insulin Glargine Daily Dose [1] 
[Units: Units per day]
Mean (Standard Deviation)
 44.24  (19.86)   43.44  (18.84)   43.84  (19.34) 
[1] Insulin glargine average daily dose at Baseline is the average daily dose for the week prior to Visit 12 (Week -1).
Treatment Satisfaction Score (Diabetes Treatment Satisfaction Questionnaire [DTSQ]) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 31.5  (5.1)   31.7  (4.5)   31.6  (4.8) 
[1] DTSQ: 8-item questionnaire to assess treatment satisfaction and patient perception of hyper and hypoglycemia. Each question (Q) scored on a Likert scale from 0 (worst case) to 6 (best case) except Q2 and 3 where 0 (best case) to 6 (worst case). Six items (Q1 and 4-8) measured treatment satisfaction and were summed to calculate treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied). Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively and lower score represented good perceived blood glucose control.
Duration of Diabetes [1] 
[Units: Years]
Mean (Standard Deviation)
 8.72  (5.82)   9.62  (6.03)   9.17  (5.94) 
[1] Duration of diabetes at screening is reported.
Metformin Daily Dose 
[Units: Milligram (mg) per day]
Mean (Standard Deviation)
 2058.1  (430.6)   2039.2  (405.3)   2048.7  (417.8) 
Number of Patients With Thiazolidinedione (TZD) use at Baseline 
[Units: Participants]
     
Yes   27   27   54 
No   196   196   392 
Body Mass Index (BMI) [1] 
[Units: Kilogram per square meter (kg/m^2)]
Mean (Standard Deviation)
 31.65  (6.01)   31.99  (6.63)   31.82  (6.32) 
[1] BMI was calculated by dividing body weight by the height squared.
Number of Patients With Categorical BMI 
[Units: Participants]
     
Less than 30   103   103   206 
Greater than or equal to 30   120   120   240 


  Outcome Measures
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1.  Primary:   Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24   [ Time Frame: Baseline, Week 24 ]

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

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

4.  Secondary:   Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24   [ Time Frame: Baseline, Week 24 ]

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

6.  Secondary:   Change From Baseline in Average Insulin Glargine Daily Dose at Week 24   [ Time Frame: Baseline, Week 24 ]

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

8.  Secondary:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24   [ Time Frame: Week 24 ]

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

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

11.  Secondary:   Change From Baseline in Treatment Satisfaction Score (Sum of Items 1, 4, 5, 6, 7 and 8 of DTSQ) at Week 24   [ Time Frame: Baseline, Week 24 ]

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

13.  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


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00975286     History of Changes
Other Study ID Numbers: EFC10781
EudraCT : 2008-007335-40
Study First Received: September 10, 2009
Results First Received: August 18, 2016
Last Updated: August 18, 2016