Efficacy and Safety of BI 1356 in Combination With Metformin in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00622284
First received: February 13, 2008
Last updated: December 11, 2013
Last verified: December 2013
Results First Received: November 30, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Placebo identical to BI 1356 5mg
Drug: Placebo identical to Glimepiride 1mg or 2mg or 3mg or 4 mg
Drug: BI 1356
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
There were in total 1560 patients randomised in the study. Of these, 1 patient was not treated. The remaining 8 patients not accounted for in the treated set were removed from all study analyses (explained in trial report) due to major good-clinical-practice violations at the site, and the inability to verify the validity of any patient level data.

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
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin

Participant Flow:   Overall Study
    Linagliptin     Glimepiride  
STARTED     776 [1]   775 [2]
COMPLETED     587 [3]   604 [3]
NOT COMPLETED     189     171  
Lack of Efficacy                 45                 15  
Adverse Event                 61                 90  
Protocol Violation                 12                 5  
Lost to Follow-up                 11                 13  
Withdrawal by Subject                 27                 24  
Other reason (not specified)                 33                 24  
[1] Number who started treatment. One patient in the Linagliptin group was randomized but not treated.
[2] Number who started treatment.
[3] Number who completed treatment.



  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
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin
Total Total of all reporting groups

Baseline Measures
    Linagliptin     Glimepiride     Total  
Number of Participants  
[units: participants]
  776     775     1551  
Age  
[units: Years]
Mean ± Standard Deviation
  59.8  ± 9.4     59.8  ± 9.4     59.8  ± 9.4  
Gender  
[units: Patients]
     
Female     314     304     618  
Male     462     471     933  
Body mass index (BMI) continuous  
[units: kg/m^2]
Mean ± Standard Deviation
  30.21  ± 4.77     30.31  ± 4.57     30.26  ± 4.67  
Weight  
[units: kg]
Mean ± Standard Deviation
  86.14  ± 17.57     86.77  ± 16.69     86.46  ± 17.14  
Glycosylated haemoglobin (HbA1c) [1]
[units: Percent]
Mean ± Standard Deviation
  7.69  ± 0.88     7.69  ± 0.86     7.69  ± 0.87  
Fasting blood plasma glucose (FPG) [2]
[units: mg/dL]
Mean ± Standard Deviation
  164.46  ± 42.83     166.09  ± 42.05     165.27  ± 42.43  
[1] Baseline HbA1c was available for 1519 patients in the Full Analysis Set (FAS), 764 treated with Linagliptin and 755 patients treated with Glimepiride.
[2] Baseline fasting plasma glucose (FPG) was available for 1475 patients in the FAS, 740 treated with Linagliptin and 735 patients treated with Glimepiride.



  Outcome Measures
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1.  Primary:   HbA1c Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

2.  Primary:   HbA1c Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

3.  Secondary:   Body Weight Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

4.  Secondary:   Body Weight Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

5.  Secondary:   Incidence of Hypoglycaemic Events up to 52 Weeks   [ Time Frame: Week 52 ]

6.  Secondary:   Incidence of Hypoglycaemic Events up to 104 Weeks   [ Time Frame: Week 104 ]

7.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

8.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

9.  Secondary:   Percentage of Patients With HbA1c <7.0% at Week 52   [ Time Frame: Week 52 ]

10.  Secondary:   Percentage of Patients With HbA1c <7.0% at Week 104   [ Time Frame: Week 104 ]

11.  Secondary:   Percentage of Patients With HbA1c <6.5% at Week 52   [ Time Frame: Week 52 ]

12.  Secondary:   Percentage of Patients With HbA1c <6.5% at Week 104   [ Time Frame: Week 104 ]

13.  Secondary:   Percentage of Patients With HbA1c Lowering by 0.5% at Week 104   [ Time Frame: Week 104 ]

14.  Secondary:   2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

15.  Secondary:   HbA1c Change at Week 4   [ Time Frame: Baseline and week 4 ]

16.  Secondary:   HbA1c Change at Week 8   [ Time Frame: Baseline and week 8 ]

17.  Secondary:   HbA1c Change at Week 12   [ Time Frame: Baseline and week 12 ]

18.  Secondary:   HbA1c Change at Week 16   [ Time Frame: Baseline and week 16 ]

19.  Secondary:   HbA1c Change at Week 28   [ Time Frame: Baseline and week 28 ]

20.  Secondary:   HbA1c Change at Week 40   [ Time Frame: Baseline and week 40 ]
  Hide Outcome Measure 20

Measure Type Secondary
Measure Title HbA1c Change at Week 40
Measure Description No text entered.
Time Frame Baseline and week 40  
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.
The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.

Reporting Groups
  Description
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin

Measured Values
    Linagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  764     755  
HbA1c Change at Week 40  
[units: Percent]
Mean ± Standard Deviation
  -0.42  ± 0.77     -0.69  ± 0.83  

No statistical analysis provided for HbA1c Change at Week 40



21.  Secondary:   HbA1c Change at Week 52   [ Time Frame: Baseline and week 52 ]

22.  Secondary:   HbA1c Change at Week 65   [ Time Frame: Baseline and week 65 ]

23.  Secondary:   HbA1c Change at Week 78   [ Time Frame: Baseline and week 78 ]

24.  Secondary:   HbA1c Change at Week 91   [ Time Frame: Baseline and week 91 ]

25.  Secondary:   HbA1c Change at Week 104   [ Time Frame: Baseline and week 104 ]

26.  Secondary:   Change in Baseline Lipid Parameter Cholesterol at Week 104   [ Time Frame: Baseline and week 104 ]

27.  Secondary:   Change in Baseline Lipid Parameter HDL at Week 104   [ Time Frame: Baseline and week 104 ]

28.  Secondary:   Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104   [ Time Frame: Baseline and week 104 ]

29.  Secondary:   Change in Baseline Lipid Parameter Triglyceride at Week 104   [ Time Frame: Baseline and week 104 ]


  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
With the exception of HbA1c<6.5% and HbA1c<7.0% at Week52, all other endpoints are presented in the Week52 repeated analysis within the final clinical trial report, where discrepancies between interim and final results are also explained.


  More Information