Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00359762
First received: July 31, 2006
Last updated: September 17, 2013
Last verified: September 2013
Results First Received: March 29, 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
Drug: glimepiride

  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
Patients meeting defined failure of HbA1c control (primary endpoint) in Study Period II were eligible for entry to Study Period III

Reporting Groups
  Description
Period II, Exen + Met Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
Period II, Glim + Met Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
Period III, Exen + Met + Glim - Randomized Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
Period III, Exen + Met + Pio or Rosi - Randomized Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
Period III, Glim + Met + Exen - Not Randomized Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III

Participant Flow for 2 periods

Period 1:   Period II
    Period II, Exen + Met     Period II, Glim + Met     Period III, Exen + Met + Glim - Randomized     Period III, Exen + Met + Pio or Rosi - Randomized     Period III, Glim + Met + Exen - Not Randomized  
STARTED     515     514     0     0     0  
Intent to Treat (ITT) Safety Population     511     508     0     0     0  
ITT Efficacy Population     490     487     0     0     0  
Met Primary Endpoint     203     262     0     0     0  
Without Treatment Failure     138     124     0     0     0  
COMPLETED     341     386     0     0     0  
NOT COMPLETED     174     128     0     0     0  
Adverse Event                 49                 17                 0                 0                 0  
Protocol Violation                 11                 18                 0                 0                 0  
Physician Decision                 23                 17                 0                 0                 0  
Death                 4                 2                 0                 0                 0  
Lack of Efficacy                 8                 11                 0                 0                 0  
Lost to follow up                 5                 5                 0                 0                 0  
Entry Criteria Not Met                 4                 8                 0                 0                 0  
Subject Decision                 70                 50                 0                 0                 0  

Period 2:   Period III
    Period II, Exen + Met     Period II, Glim + Met     Period III, Exen + Met + Glim - Randomized     Period III, Exen + Met + Pio or Rosi - Randomized     Period III, Glim + Met + Exen - Not Randomized  
STARTED     0     0     77     77     166  
Extension ITT Safety Population     0     0     74     76     166  
Extension ITT Efficacy Population     0     0     73     75     164  
COMPLETED     0     0     48     47     101  
NOT COMPLETED     0     0     29     30     65  
Protocol Violation                 0                 0                 5                 3                 8  
Adverse Event                 0                 0                 3                 4                 10  
Physician Decision                 0                 0                 5                 9                 15  
Lack of Efficacy                 0                 0                 7                 5                 9  
Lost to follow up                 0                 0                 1                 1                 2  
Entry Criteria Not Met                 0                 0                 1                 0                 1  
Subject Decision                 0                 0                 7                 8                 20  



  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.
No text entered.

Reporting Groups
  Description
Exen + Met Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
Glim + Met Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
Total Total of all reporting groups

Baseline Measures
    Exen + Met     Glim + Met     Total  
Number of Participants  
[units: participants]
  490     487     977  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     388     389     777  
>=65 years     102     98     200  
Age  
[units: years]
Mean ± Standard Deviation
  56.1  ± 10.03     56.8  ± 9.14     56.4  ± 9.60  
Gender  
[units: participants]
     
Female     218     235     453  
Male     272     252     524  
Glycosylated hemoglobin (HbA1c)  
[units: percentage of total hemoglobin]
Mean ± Standard Deviation
  7.4  ± 0.69     7.4  ± 0.71     7.4  ± 0.70  
Weight  
[units: kg]
Mean ± Standard Deviation
  92.8  ± 16.70     91.1  ± 14.78     92.0  ± 15.78  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Patients With Treatment Failure   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

2.  Primary:   Time to Treatment Failure   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

3.  Secondary:   Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3   [ Time Frame: Year 3 in Period II ]

4.  Secondary:   Change in HOMA-B From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

5.  Secondary:   Fasting Proinsulin/Insulin Ratio at Year 3   [ Time Frame: Year 3 in Period II ]

6.  Secondary:   Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

7.  Secondary:   Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3   [ Time Frame: Year 3 in Period II ]

8.  Secondary:   Change in DI30/DG30 Ratio From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

9.  Secondary:   Disposition Index at Year 3   [ Time Frame: Year 3 in Period II ]

10.  Secondary:   Change in Disposition Index From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

11.  Secondary:   Change in HbA1c From Baseline to Year 3   [ Time Frame: Baseline, Year 3 in Period II ]

12.  Secondary:   Change in HbA1c From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

13.  Secondary:   Fasting Plasma Glucose at Year 3   [ Time Frame: Year 3 in Period II ]

14.  Secondary:   Change in Fasting Plasma Glucose From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

15.  Secondary:   Postprandial (2 Hours) Plasma Glucose at Year 3   [ Time Frame: Year 3 in Period II ]

16.  Secondary:   Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

17.  Secondary:   Change in Body Weight From Baseline to Year 3   [ Time Frame: Baseline, Year 3 in Period II ]

18.  Secondary:   Systolic Blood Pressure at Year 3   [ Time Frame: Year 3 in Period II ]

19.  Secondary:   Diastolic Blood Pressure at Year 3   [ Time Frame: Year 3 in Period II ]

20.  Secondary:   Heart Rate at Year 3   [ Time Frame: Year 3 in Period II ]

21.  Secondary:   Triglycerides at Year 3   [ Time Frame: Year 3 in Period II ]
  Hide Outcome Measure 21

Measure Type Secondary
Measure Title Triglycerides at Year 3
Measure Description Triglycerides at Year 3.
Time Frame Year 3 in Period II  
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 Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Reporting Groups
  Description
Exen + Met Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
Glim + Met Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Measured Values
    Exen + Met     Glim + Met  
Number of Participants Analyzed  
[units: participants]
  178     193  
Triglycerides at Year 3  
[units: mmol/L]
Least Squares Mean ± Standard Error
  1.69  ± 0.065     1.95  ± 0.062  


Statistical Analysis 1 for Triglycerides at Year 3
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0042
Least Squares Mean Difference [4] -0.26
Standard Error of the mean ± 0.089
95% Confidence Interval ( -0.43 to -0.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  MMRM analysis includes treatment, visit, and treatment by visit interaction, and baseline value as a covariate. The unstructured covariance matrix was used.
[2] Other relevant method 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.



22.  Secondary:   Total Cholesterol at Year 3   [ Time Frame: Year 3 in Period II ]

23.  Secondary:   High-density Lipoprotein (HDL) Cholesterol at Year 3   [ Time Frame: Year 3 in Period II ]

24.  Secondary:   Hypoglycemia Rate Per Year   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

25.  Secondary:   Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III   [ Time Frame: Baseline in Period III, Year 2 in Period III ]

26.  Secondary:   Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III   [ Time Frame: Baseline in Period III, Year 2 in Period III ]

27.  Secondary:   Hypoglycemia Rate Per Year in Period III   [ Time Frame: Start of Period III to end of study ]


  Serious Adverse Events


  Other Adverse Events


  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
Only patients who reached primary endpoint 12 months or more before the projected end of the study could enter period III.  


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 Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00359762     History of Changes
Other Study ID Numbers: H8O-EW-GWBE
Study First Received: July 31, 2006
Results First Received: March 29, 2012
Last Updated: September 17, 2013
Health Authority: Austria: Federal Ministry for Health and Women
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Mexico: Ministry of Health
Poland: Ministry of Health
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medical Board