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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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

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 ]
  Show Outcome Measure 2

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 ]
  Show Outcome Measure 4

5.  Secondary:   Change in Total Cholesterol From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Show Outcome Measure 5

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 ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Ratio of Fasting Triglycerides at Week 26 to Baseline
Measure Description Ratio of fasting triglycerides (measured in mmol/L) treatment endpoint at Week 26 to baseline. Log(Postbaseline fasting triglycerides) - log(Baseline fasting triglycerides); change from baseline to the treatment endpoint at Week 26 is presented as ratio of Week 26 to baseline.
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. All observed data from all scheduled visits (including early termination visits) were included in the MMRM analysis. Data collected at the early termination visits were mapped into the following scheduled visits.

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]
 		  395     385  
Ratio of Fasting Triglycerides at Week 26 to Baseline  
[units: ratio]
Least Squares Mean ± Standard Error 		  0.97  ± 0.02     0.89  ± 0.02  


Statistical Analysis 1 for Ratio of Fasting Triglycerides at Week 26 to Baseline
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] <.001
Least Squares Mean Difference [4] 1.09
Standard Error of the mean ± 0.03
95% Confidence Interval ( 1.04 to 1.15 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Fasting triglycerides were logarithm-transformed and the change at Week 26 to baseline, expressed as the ratio, was analyzed using a MMRM model with treatment, baseline fasting triglycerides, HbA1c stratum, country, background OAD, week of visit, and treatment-by-week interaction as fixed effects and subject and error as random effects.
[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.
[4] Other relevant estimation information:
  No text entered.



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 ]
  Show Outcome Measure 10


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

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

Serious Adverse Events
    Exenatide Once Weekly     Liraglutide Once Daily  
Total, serious adverse events      
# participants affected / at risk     13/461 (2.82%)     7/450 (1.56%)  
Cardiac disorders      
Coronary artery disease * 1    
# participants affected / at risk     1/461 (0.22%)     1/450 (0.22%)  
Myocardial infarction * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Atrial fibrillation * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Ear and labyrinth disorders      
Hearing impaired * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Gastrointestinal disorders      
Gastrointestinal disorder * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Gastrointestinal haemorrhage * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Pancreatitis acute * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Constipation * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Diarrhoea * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Vomiting * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
General disorders      
Impaired healing * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Chest pain * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Hepatobiliary disorders      
Cholecystitis acute * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Cholelithiasis * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Immune system disorders      
Anaphylactic reaction * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Infections and infestations      
Appendicitis * 1    
# participants affected / at risk     2/461 (0.43%)     0/450 (0.00%)  
Injury, poisoning and procedural complications      
Joint dislocation * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Patella fracture * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Musculoskeletal and connective tissue disorders      
Intervertebral disc protrusion * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Prostate cancer * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Spinal cord neoplasm * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
Nervous system disorders      
Cerebrovascular accident * 1    
# participants affected / at risk     1/461 (0.22%)     1/450 (0.22%)  
Brain stem infarction * 1    
# participants affected / at risk     0/461 (0.00%)     1/450 (0.22%)  
Psychiatric disorders      
Depression * 1    
# participants affected / at risk     1/461 (0.22%)     0/450 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 14.0




  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
Australia: Therapeutic Goods Administration (TGA)
Austria: Agency for Health and Food Safety, Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization for Medicines
Hungary: National Institute of Pharmacy
India: Ministry of Health: Drug Control General of India (DCGI)
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Mexico: National Institute of Public Health, Health Secretariat
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española del Medicamento y Productos Sanitarios
Taiwan: Department of Health