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Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:
NCT01029886
First received: December 8, 2009
Last updated: January 14, 2013
Last verified: January 2013
History of Changes
Results First Received: February 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: exenatide once weekly
Drug: liraglutide

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily

Participant Flow:   Overall Study
    Exenatide Once Weekly     Liraglutide Once Daily  
STARTED     461     451  
Intent to Treat (ITT)     461     450  
COMPLETED     400     391  
NOT COMPLETED     61     60  
Adverse Event                 12                 25  
Lost to Follow-up                 1                 0  
Physician Decision                 2                 6  
Protocol Violation                 17                 5  
Withdrawal by Subject                 8                 18  
Entry Criteria Not Met                 13                 5  
Sponsor Decision                 1                 0  
Loss Glucose Control                 7                 1  



  Baseline Characteristics
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Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily
Total Total of all reporting groups

Baseline Measures
    Exenatide Once Weekly     Liraglutide Once Daily     Total  
Number of Participants  
[units: participants]
 		  461     450     911  
Age  
[units: participants]
 		     
<=18 years     0     0     0  
Between 18 and 65 years     386     360     746  
>=65 years     75     90     165  
Age  
[units: years]
Mean ± Standard Deviation 		  56.6  ± 9.43     56.7  ± 9.59     56.6  ± 9.51  
Gender  
[units: participants]
 		     
Female     207     205     412  
Male     254     245     499  
Glycosylated hemoglobin (HbA1c)  
[units: percentage of total hemoglobin]
Mean ± Standard Deviation 		  8.45  ± 1.014     8.43  ± 0.996     8.44  ± 1.004  
Weight  
[units: kg]
Mean ± Standard Deviation 		  90.88  ± 19.472     91.13  ± 19.118     91.00  ± 19.288  
Background Oral Antidiabetic Agent (OAD)  
[units: participants]
 		     
Metformin (MET)     150     136     286  
Sulfonylurea (SU)     18     18     36  
Pioglitazone (PIO)     1     0     1  
MET+SU     275     277     552  
MET+PIO     16     18     34  
MET+SU+PIO     1     1     2  



  Outcome Measures
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1.  Primary:   Change in HbA1c From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 1

2.  Secondary:   Percentage of Patients Achieving HbA1c <7.0% at Week 26   [ Time Frame: Baseline, Week 26 ]
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Measure Type Secondary
Measure Title Percentage of Patients Achieving HbA1c <7.0% at Week 26
Measure Description Percentage of patients achieving HbA1c <7.0% at treatment endpoint at Week 26.
Time Frame Baseline, Week 26  
Safety Issue No  

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.
ITT Population. Missing data at endpoint was imputed using last observation carried forward approach.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily

Measured Values
    Exenatide Once Weekly     Liraglutide Once Daily  
Number of Participants Analyzed  
[units: participants]
 		  461     450  
Percentage of Patients Achieving HbA1c <7.0% at Week 26  
[units: percentage of patients]
 		  52.7     60.2  


Statistical Analysis 1 for Percentage of Patients Achieving HbA1c <7.0% at Week 26
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.011
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Percentage of patients achieving HbA1c <7.0% at Week 26 were compared between treatments using a Cochran-Mantel-Haenszel test, in which HbA1c stratum, country, and background OAD served as stratification factors.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Change in Fasting Serum Glucose From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 3

4.  Secondary:   Change in Body Weight From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
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5.  Secondary:   Change in Total Cholesterol From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
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6.  Secondary:   Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 6

7.  Secondary:   Ratio of Fasting Triglycerides at Week 26 to Baseline   [ Time Frame: Baseline, Week 26 ]
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8.  Secondary:   Change in Systolic Blood Pressure (SBP) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 8

9.  Secondary:   Change in Diastolic Blood Pressure (DBP) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 9

10.  Secondary:   Assessment of Event Rate of Treatment-emergent Hypoglycemic Events   [ Time Frame: Baseline to Week 26 ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title Assessment of Event Rate of Treatment-emergent Hypoglycemic Events
Measure Description Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT.
Time Frame Baseline to Week 26  
Safety Issue Yes  

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.
ITT Population.

Reporting Groups
  Description
Exenatide Once Weekly With SU Use at Screening Subcutaneous injection, 2mg, once weekly and with SU use at screening
Liraglutide Once Daily With SU Use at Screening Subcutaneous injection, forced titration to 1.8mg, once daily and with SU use at screening
Exenatide Once Weekly Without SU Use at Screening Subcutaneous injection, 2mg, once weekly and without SU use at screening
Liraglutide Once Daily Without SU Use at Screening Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening

Measured Values
    Exenatide Once Weekly With SU Use at Screening     Liraglutide Once Daily With SU Use at Screening     Exenatide Once Weekly Without SU Use at Screening     Liraglutide Once Daily Without SU Use at Screening  
Number of Participants Analyzed  
[units: participants]
 		  294     296     167     154  
Assessment of Event Rate of Treatment-emergent Hypoglycemic Events  
[units: events per subject-year]
Mean ± Standard Error 		       
Major Hypoglycemia     0.00  ± 0.000     0.00  ± 0.000     0.00  ± 0.000     0.00  ± 0.000  
Minor Hypoglycemia     0.76  ± 0.143     0.55  ± 0.126     0.67  ± 0.417     0.05  ± 0.026  

No statistical analysis provided for Assessment of Event Rate of Treatment-emergent Hypoglycemic Events




  Serious Adverse Events
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  Other Adverse Events
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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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-877-285-4559
e-mail: clinicaltrials@amylin.com


No publications provided by Amylin Pharmaceuticals, LLC.

Publications automatically indexed to this study:


Responsible Party: Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier: NCT01029886     History of Changes
Other Study ID Numbers: H8O-MC-GWDE
Study First Received: December 8, 2009
Results First Received: February 14, 2012
Last Updated: January 14, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
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Czech Republic: State Institute for Drug Control
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