Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure (EAGLE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01117350
First received: May 4, 2010
Last updated: March 5, 2014
Last verified: March 2014
Results First Received: October 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Insulin glargine
Drug: Liraglutide
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 first patient was enrolled on July 23, 2010. The 24-week comparative period was completed on October 5, 2012.

The extension period was initiated on March 24, 2011 and completed on March 6, 2013.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1456 patients were screened in 136 centers, in 17 countries (Austria, Brazil, Canada, Czech Republic, Finland, France, Greece, Ireland, Israel, Mexico, Netherlands, Russian Federation Slovakia, Spain, Sweden, Turkey, USA). Among them, 478 (32.8%) patients were not randomized (main reason was Glycosylated Haemoglobin A1c out of range).

Reporting Groups
  Description
Insulin Glargine Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days
Liraglutide (Comparative Period)/ Insulin Glargine (Extension)

Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24 (comparative period)

For patients included in the extension period: Insulin Glargine (dosing same as above)


Participant Flow for 2 periods

Period 1:   Comparative Period
    Insulin Glargine     Liraglutide (Comparative Period)/ Insulin Glargine (Extension)  
STARTED     489 [1]   489  
TREATED = Safety Population     484 [2]   481  
mITT Population     474 [3]   470  
COMPLETED     447     414  
NOT COMPLETED     42     75  
Not Treated                 5                 8  
Adverse Event                 6                 33  
Lost to Follow-up                 11                 7  
Withdrawal by Subject                 9                 13  
Protocol Violation                 8                 12  
Lack of Efficacy                 1                 0  
Physician Decision                 0                 1  
Move to another city/country                 2                 1  
[1] STARTED: randomized
[2] Safety population: all randomized and treated patients (received at least one dose)
[3] modified Intent-To-Treat population: treated patients with at least one efficacy post-baseline value

Period 2:   Extension Period
    Insulin Glargine     Liraglutide (Comparative Period)/ Insulin Glargine (Extension)  
STARTED     0     210 [1]
TREATED = Safety Population (Extension)     0     160 [2]
mITT Population (Extension)     0     154 [3]
COMPLETED     0     147  
NOT COMPLETED     0     63  
Not included in extension, not treated                 0                 50  
Adverse Event                 0                 2  
Protocol Violation                 0                 2  
Lost to Follow-up                 0                 2  
Withdrawal by Subject                 0                 3  
Lack of Efficacy                 0                 2  
Inclusion criteria not respected                 0                 1  
Prohibited medication                 0                 1  
[1] STARTED: patients having completed the comparative period and eligible for the extension period
[2] Safety population (extension): treated with insulin glargine during the extension period
[3] mITT (extension): treated patients with at least 1 efficacy value both at entry and during extension



  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.
Modified-Intent-to-treat (mITT) population: all patients who were randomized, received at least one dose of Interventional Product (IP), and had at least one post-baseline assessment during comparative period of any primary or secondary efficacy variables

Reporting Groups
  Description
Insulin Glargine Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.
Total Total of all reporting groups

Baseline Measures
    Insulin Glargine     Liraglutide     Total  
Number of Participants  
[units: participants]
  474     470     944  
Age  
[units: years]
Mean ± Standard Deviation
  57.07  ± 8.78     57.44  ± 8.85     57.25  ± 8.81  
Gender  
[units: participants]
     
Female     224     207     431  
Male     250     263     513  
Body Mass Index (BMI) at week -2  
[units: kg/m²]
Mean ± Standard Deviation
  32.00  ± 4.24     31.75  ± 4.12     31.88  ± 4.18  
Duration of Type 2 diabetes  
[units: years]
Median ( Inter-Quartile Range )
  8.54  
  ( 5.20 to 12.38 )  
  8.41  
  ( 4.80 to 11.69 )  
  8.49  
  ( 4.94 to 12.17 )  
At least one diabetic late complication [1]
[units: participants]
     
Yes     212     223     435  
No     262     247     509  
Glycosylated Hemoglobin A1c (HbA1c) at week -2  
[units: percent]
Mean ± Standard Deviation
  9.04  ± 1.10     9.11  ± 1.09     9.07  ± 1.09  
[1] Diabetic late complications: myocardial infarction, angina pectoris, coronary artery disease, heart failure, stroke, transient ischemic attack, peripheral vascular disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period   [ Time Frame: week 12, week 24 ]

2.  Secondary:   Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period   [ Time Frame: baseline (week -2), week 12, week 24 ]

3.  Secondary:   Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period   [ Time Frame: baseline (week -2), week 12, week 24 ]

4.  Secondary:   Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period   [ Time Frame: baseline (week -2), week 12, week 24 ]

5.  Secondary:   Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period   [ Time Frame: week 24, week 36, week 48 ]

6.  Secondary:   Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period   [ Time Frame: week 36, week 48 ]

7.  Secondary:   Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period   [ Time Frame: baseline (week 0), week 6, week 12, week 18, week 24 ]

8.  Secondary:   Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period   [ Time Frame: week 24, week 30, week 36, week 48 ]

9.  Secondary:   Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period   [ Time Frame: baseline (week 0), week 12, week 24 ]

10.  Secondary:   Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period   [ Time Frame: week 24, week 36, week 48 ]

11.  Secondary:   Body Weight: Change From Baseline to the End of the Comparative Period   [ Time Frame: baseline (week 0), week 2, week 6, week 12, week 18, week 24 ]

12.  Secondary:   Body Weight: Change From Beginning to End of the Extension Period   [ Time Frame: week 24, week 30, week 36, week 48 ]

13.  Secondary:   Daily Dose of Insulin Glargine   [ Time Frame: week 1, week 2, week 6, week 12, week 24 ]

14.  Secondary:   Daily Dose of Liraglutide   [ Time Frame: week 1, week 2, week 6, week 12, week 24 ]

15.  Secondary:   Daily Dose of Insulin Glargine Administered During the Extension Period   [ Time Frame: week 30, week 36, week 48 ]

16.  Secondary:   Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period   [ Time Frame: all across the comparative period (from week 0 to week 24) ]

17.  Secondary:   Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period   [ Time Frame: all across the extension period (from week 24 to week 48) ]


  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


No publications provided


Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01117350     History of Changes
Other Study ID Numbers: LANTU_C_03680, 2010-018437-21, U1111-1116-9684
Study First Received: May 4, 2010
Results First Received: October 4, 2013
Last Updated: March 5, 2014
Health Authority: Czech Republic: State Institute for Drug Control
United States: Food and Drug Administration